Research & Clinical Trials at the Sean M. Healey & AMG Center for ALS at Mass General

At the Sean M. Healey and AMG Center for ALS at Mass General, we are committed to radical change and acceleration of converting research into enduring treatments. Find information on our research studies and enroll in clinical trials.

Research Labs

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  • Lagier-Tourenne Lab

    Clotilde Lagier-Tourenne

    Clotilde Lagier-Tourenne performs patient-oriented research to understand the molecular mechanisms driving neurodegeneration in Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) and to develop therapeutic strategies.

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  • MassGeneral Institute for Neurodegenerative Disease (MIND)

    The MassGeneral Institute for Neurodegenerative Disease (MIND) is a research center for Alzheimer’s, ALS (Lou Gehrig’s), Huntington’s, Parkinson’s and other neurodegenerative diseases. The Institute's mission is to accelerate research discoveries that will lead to treatment and cures.

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  • Neurological Clinical Research Institute

    Neurological Clinical Research Institute

    The Neurological Clinical Research Institute (NCRI) at Mass General is experienced in designing, developing, facilitating, and conducting multicenter clinical trials in Amyotrophic Lateral Sclerosis (ALS) and other neurological diseases.

  • NeuroNEXT

    NeuroNEXT science image

    The Network for Excellence in Neuroscience Clinical Trials (NeuroNEXT ) consists of a Clinical Coordinating Center (CCC) at Massachusetts General Hospital, a Data Coordinating Center (DCC) at the University of Iowa, and 25 clinical sites throughout the country.

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  • Wainger Laboratory

    Brian Wainger, MD, PhD

    The Wainger Lab at Massachusetts General Hospital focuses on how abnormalities of motor and sensory neuron physiology contribute to diseases such as ALS and chronic pain.

Find a Clinical Trial

ALS Trials at Mass General

Judi Carey, RN
Judi Carey, RN

For clinical trials and research information:

Judith Carey, RN
ALS Research Access Nurse
617-724-8995
jcarey8@partners.org

View our currently enrolling trials for opportunities to enroll in ALS research at Mass General.

ALS Trials Around the Nation

NEALS.org provides up-to-date information for finding both federally and privately funded clinical studies focusing on ALS and motor neuron diseases. You can locate both interventional trials, which examine if treatments are effective and safe under controlled environments, and observation trials, which examine people in more natural environments.

ALS Trials Around the World

Clinicaltrials.gov is the central database of virtually all clinical trials in the United States, and even contains information from other countries. The site is relatively easy to search, and will provide you with detailed information about trials in ALS to help you find trials that may be right for you.

Spanish Speakers

Learn how to navigate the clinicaltrials.gov website (Spanish).

ALS Clinical Trials

Enrolling ALS Clinical Trials

Trial of Levosimendan for ALS

Full Trial Name: Effects of Oral Levosimendan (ODM-109) on Respiratory Function in Patients with ALS

Trial Phase: 3

This Phase III research study is being done to evaluate if Levosimendan (ODM-109) can help with respiratory function in people with ALS. We also want to find out if levosimendan is safe to take without causing too many side effects in ALS. Orion Corporation Orion Pharma is the sponsor of this study. Levosimendan is contained in a capsule, which is taken orally. This study is placebo-controlled, which means that some participants will receive capsules that contain no levosimendan. Study participation will last approximately 12 months. Please contact the study team to obtain additional information about the study visits and procedures. The study team will review with the inclusion and exclusion criteria during the study, which is also available on clinicaltrials.gov.

Principal Investigator: Suma Babu, MD, MPH

Sponsor: Orion Corporation Orion Pharma

Enrollment Contact

Olivia Pijanowski
617-643-2522
opijanowski@mgh.harvard.edu


Trial of NurOwn for ALS

Full Trial Name: A Phase 3, Randomized, Double-Blind, Placebo-controlled Multicenter Study to Evaluate Efficacy and Safety of Repeated Administrations of NurOwn® (Autologous Mesenchymal Stem Cells Secreting Neurotrophic Factors) in Patients with Amyotrophic Lateral Sclerosis

Trial Phase: 3

The purpose of the study is to evaluate the safety and efficacy of transplanting self-derived mesenchymal stem cells secreting neurotrophic factors (MSC-NTF) into the cerebrospinal fluid in patients with ALS. The cells are derived from your own bone marrow and administered into your cerebrospinal fluid three times (once every 8 weeks for 16 weeks). Participation in this study will last approximately 11 months.

Principal Investigator: James Berry, MD, MPH

Sponsor: Brainstorm Cell Therapeutics

Enrollment Contact

Taylor Mezoian
617-643-0312
NurOwnPhase3@mgh.harvard.edu


Trial of AMX0035 for ALS

Full Trial Name: Evaluation of the Safety, Tolerability, Efficacy and Activity of AMX0035, a Fixed Combination of Phenylbutyrate (PB) and Tauroursodeoxycholic Acid (TUDCA), for Treatment of Amyotrophic Lateral Sclerosis (ALS)

Trial Phase: 2

This research study is being done to find out if AMX0035 can help with Amyotrophic Lateral Sclerosis (ALS). We also want to find out if AMX 0035 is safe to take without causing too many side effects. AMX0035, a combination of Phenylbutyrate (PB) and Tauroursodeoxycholic Acid (TUDCA), is not approved by the US Food and Drug Association (FDA). This means that AMX0035 can only be used in research studies. This is the first use of the combination drug AMX0035 in humans. However, the individual components of the drug, PB and TUDCA, have been studied in small clinical trials of patients with ALS. This research study will compare AMX0035 to placebo. Participants will receive study drug for a total of 24 weeks, followed by a telephone call about 30 days from the final study visit. During this time, we will ask participants to make up to seven study visits to the clinic and four telephone calls. Overall participants may be in the research study for about 8 months.

Principal Investigator: James Berry, MD, MPH

Sponsor: Amylyx Pharmaceuticals Inc.

Enrollment Contact

Aileen Shaughnessy
617-724-9196
anshaughnessy@mgh.harvard.edu


Trial of Inosine for ALS

Full Trial Name: Safety of Urate Elevation in Amyotrophic Lateral Sclerosis (ALS) (SurE ALS 2)

Trial Phase: 2

Researchers are currently enrolling people with ALS in a research study which is evaluating the safety of Inosine, a supplement that is used to raise blood levels of uric acid. We are doing this research study to find out if inosine is safe to take without causing too many side effects in people with amyotrophic lateral sclerosis (ALS). When people take inosine, their levels of urate, a natural antioxidant, will be increased. Higher levels of uric acid have been correlated with slower disease progression in individuals with ALS Your participation in this study would be at least 27 weeks. The purpose of the research study is to determine whether inosine is safe and tolerable for patients with Amyotrophic Lateral Sclerosis (ALS). While taking the study drug, participants will be asked to complete several tests and utilize a mobile application to collect information on tasks. From this study, the researchers hope to learn more about ALS and its treatment. Participants must be at least 18 years of age.

Principal Investigator: Katharine Nicholson, MD

Sponsor: Sala Foundation

Enrollment Contact

Jianing Liu
617-726-1880
jliu45@partners.org


Trial of RNS60 for ALS

Full Trial Name: The Effects of RN S60 on ALS Biomarkers

Trial Phase: 2

We are doing this trial to find out the effects of RNS60 on biomarkers in people with amyotrophic lateral sclerosis (ALS). Biomarkers are substances in the body that can be measured and evaluated as indicators of the body’s biological processes. We will study components in blood that may be affected by RNS60 and how it might be related to ALS. People who enroll in this trial will receive either RNS60 or placebo for 24 weeks. During this time, you will be asked to make weekly in-person study visits to MGH. You will also receive a supply of RNS60 or placebo to take at home once per day using a nebulizer.

Principal Investigator: Sabrina Paganoni, MD

Sponsor: Revalasio

Enrollment Contact

Michael Doyle
617-724-7398
mdoyle@mgh.harvard.edu


Trial of BIIB067 for SOD1-ALS

Full Trial Name: A Phase 1, Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of BIIB067 Administered to Adult Subjects with Amyotrophic Lateral Sclerosis

Trial Phase: 1

We are doing this research study to find out about the safety and tolerability of the study drug BIIB067. The study is funded by Biogen MA Inc. This study is recruiting patients with SOD1-Amyotrophic Lateral Sclerosis (SOD1-ALS) with a forced vital capacity greater than or equal to 50% of predicted value. Participation in the study will last for approximately 31 weeks and will include an overnight stay at MGH in addition to in person visits. The study team can provide additional information on the number of required visits during your initial visit. There are additional inclusion/exclusion criteria that the study team will review with you in more detail.

Principal Investigator: Nazem Atassi, MD, MMSc

Sponsor: Biogen MA Inc.

Enrollment Contact

Michael Doyle
617-724-7398
mdoyle@mgh.harvard.edu


Trial of C9ORF72 ASO for ALS

Full Trial Name: A Phase 1 Multiple-Ascending-Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of BIIB078 Administered Intrathecally to Adults with C9ORF72-Associated Amyotrophic Lateral Sclerosis

Trial Phase: 1

We are doing this research study to find out about the safety and tolerability of the study drug BIIB078. The study is funded by Biogen MA Inc. This study is recruiting patients with C9ORF72-Associated Amyotrophic Lateral Sclerosis (ALS) with a slow vital capacity greater than or equal to 50% of predicted value. Participation in the study will last for approximately 31 weeks and will include an overnight stay at MGH in addition to in person visits. The study team can provide additional information on the number of required visits during your initial visit. There are additional inclusion/exclusion criteria that the study team will review with you in more detail if you are interested in participating. For more information regarding this trial, or to further discuss how to participate, please contact the following our study coordinator below.

Principal Investigator: Nazem Atassi, MD, MMSc

Sponsor: Biogen MA Inc.

Enrollment Contact

Harli Weber
617-643-5376
hweber1@mgh.harvard.edu


Trial of GDC-0134 for ALS

Full Trial Name: A Phase I, Double-Blind, Randomized, Placebo-Controlled, Multicenter, Single-and Multiple-Ascending-Dose Study to Determine Initial Safety, Tolerability, and Pharmacokinetics of GDC-0134 in Patients with Amyotrophic Lateral Sclerosis

Trial Phase: 1

The purpose of the research study is to determine whether the drug GDC-0134 is safe and tolerable for patients with ALS. This study will also look at the amount of study drug in your blood after different doses are taken. Participation in this study will last approximately three to five months. Participants may have the opportunity to participate in more than one dosing period. Each dosing period will require one four-night stay in the hospital during GDC-0134 dosing, and a follow up visit at one week and two weeks post-dosing. Participants must be at least 18 years of age, and able to comply with study procedures. We will review a complete list of the study’s inclusion

Principal Investigator: Nazem Atassi, MD, MMSc

Sponsor: Genentech

Enrollment Contact

Brixhilda Dedi
617-726-4284
bdedi@mgh.harvard.edu


Enrolling Studies: Clinical Research to Understand ALS

Trial of Answer ALS

+Amyotrophic Lateral Sclerosis
+Primary Lateral Sclerosis

Full Trial Name: Answer ALS: Individualized Initiative for ALS Discovery

Answer ALS is a research study that is helping to create the largest-ever collection of stem cell lines derived from the blood of people with ALS. The collection of cells will be linked to detailed clinical information and a repository of biospecimens. The cell lines and clinical data will be studied in laboratories from across the country that have partnered for this project. Data from these labs will be analyzed individually and together using “big data” analysis techniques to demonstrate why and how motor neurons are affected by ALS, to identify biologically unique subgroups of people with ALS, and to search for new targets for drug therapy. Participants must be at least 18 years of age, and able to follow study tasks. Participants will be asked to come to MGH approximately every 3 months for 1 year, and will be followed by telephone thereafter for as long as they are willing.

Principal Investigator: James Berry, MD, MPH

Sponsor: ALS Finding a Cure

Enrollment Contact

Brixhilda Dedi
617-726-4284
bdedi@mgh.harvard.edu


Trial of Answer ALS App

+Amyotrophic Lateral Sclerosis
+Primary Lateral Sclerosis

Full Trial Name: Smartphone Application and Wearable Activity Monitor to Track Progression of Amyotrophic Lateral Sclerosis

The purpose of this research study is to see if progression of diseases in people with Amyotrophic Lateral Sclerosis (ALS) can be tracked using a smart phone application (app) over time. You are being asked to participate because you are already enrolled in Answer ALS and this is a sub-study of that study.

There are 7 tasks in the app. You will be asked to perform one task a day. The tasks are:

  • Voice recording
  • Finger tapping - Right and Left
  • Finger tracing - Right and Left
  • Tilt tracing - Right and Left

We are asking that you continue to use the app for as long as you are able. The duration of this study is approximately 12 months. During this time, you will have two in person visits and I will contact you by phone or email in 2 weeks and then again at months 2, 6, and 9 months to see if you are having any issues and to get any feedback about the app you would like to contribute. Please contact us if you are interested in hearing more details and/or if you would like to know if you are eligible to participate in this study.

Principal Investigator: James Berry, MD, MPH

Sponsor: ALS Finding a Cure, The Robert Packard Center, The Answer ALS Foundation

Enrollment Contact

Brixhilda Dedi
617-726-4284
bdedi@mgh.harvard.edu


Trial of DIALS

+ Asymptomatic first-degree adult relatives of people with familial ALS

Full Trial Name: Dominant Inherited ALS (DIALS) Network

This study is recruiting participants who do not have any neurological symptoms, but who have a first-degree relative with ALS caused by a mutation. The purpose of the research study is to study a population at risk for developing ALS. The information collected in this study will further our understanding of underlying early disease changes to allow for development of novel therapeutics that target the earliest changes in ALS and allow for possible disease prevention.

Through this study you will be offered genetic counseling, and genetic testing for all currently known genes that may cause ALS. In addition, the study will be performing regular, longitudinal evaluations (e.g. blood samples, questionnaire completion; pulmonary and strength testing etc.,) for a period of several years.  Study visits will be completed at the Neurological Clinical Research Institute at Massachusetts General Hospital.

Principal Investigator: Katharine Nicholson, MD

Sponsor: ALS Finding a Cure, Target ALS, ALS Association, American Academy of Neurology/Muscular Dystrophy Association

Enrollment Contact

Tiina Xu
617-643-7428
tjxu@mgh.harvard.edu


Trial of GE-179

+Amyotrophic Lateral Sclerosis
+Healthy Volunteers

Evaluation of brain N-methyl-d-aspartate receptor (NMDAR) excito-toxicity activity in ALS using novel [18F]GE-179 Positron Emission Tomography (PET) radiotracer- A pilot study

This study is recruiting participants with Amyotrophic Lateral Sclerosis (ALS), as well as people without a history of neurological disease, using MRI and PET scans to look at the brain activity of certain receptors involved in neurotransmission. Criteria include, but are not limited to, the following:

  1. Age 30 – 80
  2. No electrically powered devices in their body
  3. Able to lie flat comfortably for at least 90 minutes

The purpose of this research study is to determine whether there are differences between people with and without ALS in brain NMDA receptor activity (a channel present in nerve cells of brain and spinal cord that regulates neurotransmission). Participation in this study will involve up to 3 visits (a screening and one to two imaging sessions). The MRI and PET scans are compensated at $100 each and parking fees are waived.

Principal Investigator: Nazem Atassi, MD, MMSc and Suma Babu, MD, MPH

Sponsor: The ALS Association

Enrollment Contact

Jianing Liu
617-726-1180
jliu45@mgh.harvard.edu


Trial of Neuroinflammation (PBR28) Imaging Study

+Amyotrophic Lateral Sclerosis
+Primary Lateral Sclerosis
+Hereditary Spastic Paraplegia
+Healthy Volunteers who are known carriers of an ALS gene
+Frontotemporal Dementia +Healthy Volunteers

Full Trial Name: Glial Activation Measured by PBR28-PET in People with Neurodegenerative Diseases

The purpose of the study is to learn more about inflammation in the brains of people with Motor Neuron Disease (MND) using combined Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET). Our study will examine whether particular cells, called microglia, are hyperactive in the nervous system of people with MND, such as those individuals with ALS.

Study participation involves two visits to MGH over a maximum of three months. Participants must be between the ages of 18 and 80, be medically safe to undergo an MRI scan and be able to safely lie flat for at least 90 minutes. Additionally, participants cannot be taking any immunosuppressive medications or have a diaphragm pacing system and cannot have a diagnosis of Parkinson’s disease, Alzheimer’s disease, unstable psychiatric disease, or renal failure. All participants will be reimbursed for parking and receive compensation of $150 upon completion of each MR-PET scan. There will be additional compensation of $100 for each lumbar puncture completed by individuals with MND.

Principal Investigator: Nazem Atassi, MD, MMSc

Sponsors: Neurodegenerative Disease Pilot Study Grant, K23 NS 083715, Evan and Arlene Yegelwel Endowed Fund for Primary Lateral Sclerosis Research and Care, PET Imaging of inflammation and epigenetics in ALS (ALS ONE), Muscular Dystrophy Association, Sundry

Enrollment Contact

Catherine Cebulla
617-643-6252
ccebulla@mgh.harvard.edu


Trial of Skin Biopsy/Stem Cells for Research in MND

+Amyotrophic Lateral Sclerosis
+Primary Lateral Sclerosis
+Healthy Volunteers

Full Trial Name: Stem Cells for Research in Motor Neuron Diseases (MND)

Neurodegenerative diseases are diseases in which nerve cells of the brain and spinal cord die. There is a need to understand the cause of these diseases and to develop treatments. Recent advancements in stem cell technology have allowed us to create a person’s own nerve cells by taking a skin biopsy or blood sample. This study wants to use this new technology to make models for neurodegenerative diseases. We hope this will give us a better understanding of the diseases, enable us to use the cells for drug screening, and in the future, develop treatments.

Principal Investigator: James Berry, MD, MPH

Sponsor: Harvard Stem Cell Institute

Enrollment Contact

Alanna Farrar
617-726-4282
alfarrar@mgh.harvard.edu


Trial of SOD1 Kinetics

+Amyotrophic Lateral Sclerosis
+Healthy Volunteers

Full Trial Name: SOD1 Kinetics Measurements in SOD1 Positive ALS Patients

The purpose of this study is to find out how long the SOD1 protein stays in cerebrospinal fluid (CSF). The SOD1 protein is known to cause some forms of familial Amyotrophic Lateral Sclerosis (ALS). This study is recruiting adults with SOD1-confirmed Amyotrophic Lateral Sclerosis (ALS), Sporadic ALS (not caused by SOD1 gene), SOD1-positive asymptomatic gene carriers, and healthy adults with no medical history of neurological disease. This study involves drinking a special leucine labeled beverage for 10 days, which will be provided by the study team. Participation in this study will last approximately 4 months and requires 6 visits to MGH. Four of these visits will involve a lumbar puncture (LP). Participants must be 18 years of age, able to comply with study procedures, and be medically safe to undergo a lumbar puncture (LP).

Principal Investigator: Katharine Nicholson, MD

Sponsor: ALS Finding a Cure

Enrollment Contact

Michael Doyle
617-724-7398
mdoyle16@mgh.harvard.edu


Trial of Smartphone App for ALS

+Amyotrophic Lateral Sclerosis

Full Trial Name: Feasibility and Sensitivity of a Symptom Monitoring Application in Real Time (SMART) for Amyotrophic Lateral Sclerosis

The study asks each participant to use the smartphone application for a few minutes every day by answering a questionnaire/survey, recording your voice and/or performing an on-screen exercise. The purpose of the research study is to determine how helpful a smartphone application would be in collecting research data and to learn more about disease progression. This is a pilot study in which a smartphone application was designed and customized for use in ALS clinical trials.

Individuals with ALS will be in the study for about 12 months.

The study is currently recruiting participants who meet the following guideline: Adults with Amyotrophic Lateral Sclerosis (ALS) to download and use the smartphone application using their smartphone device running iOS 8 or higher, or Android 4.1 or higher.

Principal Investigator: James Berry, MD, MPH

Sponsor: ALS Finding a Cure

Enrollment Contact

Harli Weber
617-643-5376
hweber1@mgh.harvard.edu


Trial of Speech Motor Impairment in ALS

+Amyotrophic Lateral Sclerosis
+Primary Lateral Sclerosis
+Healthy Volunteers

Full Trial Name: Speech Motor Impairments: Coordination of tongue, lips, and Jaw

The Speech and Feeding Disorders Lab at MGH Institute of Health Professions is interested in studying the movements the face and mouth during speech, chewing and swallowing in persons diagnosed with ALS and healthy volunteers. You will be asked to fill out a health questionnaire as well as to repeat various sounds and sentences while the movements of your face and mouth are recorded. This research aims to help improve the diagnosis and treatments of ALS, and to help develop new technologies that will help improve communication for people with speech impairments.

Principal Investigator: Jordan Green, MD

Sponsors: National Institutes of Health (NIH) and the American Speech-Language-Hearing Foundation (ASHA)

Enrollment Contact

Speech and Feeding Disorders Lab
617-724-6347
speechfeedinglab@mghihp.edu


Trial of SPINE-ALS

+Amyotrophic Lateral Sclerosis
+Primary Lateral Sclerosis

Full Trial Name: Positron Emission Tomography to Characterize in vivo Neuroinflammation in the Spinal Cord in People with ALS

We are doing this research to learn more about changes in the spinal cord and brain in ALS. “Microglia” are a type of immune cell that we are particularly interested in. We would like to find out if microglia are activated in the spinal cord and brain of individuals with ALS. Special imaging techniques are now available to test for changes in microglia. Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) are two tests that allow us to take pictures and “look inside” the body without surgery. MR-PET scanners use both MRI and PET tests at the same time. The MR-PET scanner may give clearer images and more information about the inside of the body.

If you choose to take part in this study you may have 2 visits at MGH, up to 3 months apart. We will pay you $150 for completion of the spinal cord MR-PET scan. If you choose to participate in the optional brain MR-PET scan you will be paid an additional $50 for completion.

Principal Investigators: Nazem Atassi, MD, MMSc, and Suma Babu, MD, MPH

Sponsors: ALS Finding a Cure Foundation, Voyager Therapeutics

Enrollment Contact

Olivia Pijanowski
617-643-2522
opijanowski@mgh.harvard.edu

Jianing Liu
617-726-1180
Jliu45@mgh.harvard.edu

Catherine Cebulla
617-643-6252
ccebulla@mgh.harvard.edu


Trial of TRACK-ALS

+Amyotrophic Lateral Sclerosis >1 year of symptoms
+Healthy Volunteers

Full Trial Name: Imaging and BioFluid Biomarkers in Amyotrophic Lateral Sclerosis

TRACK-ALS is a multicenter, longitudinal study which aims to identify imaging and biofluid biomarkers in people with ALS to expand the understanding of disease pathology and progression. By identifying changes that occur in the blood, brain, and cerebrospinal fluid (CSF) of individuals with ALS, this pilot project has the potential to inform both diagnostic measures and drug development.

Participation in the study for those with ALS involves approximately six onsite visits to MGH every three months for up to 18 months. Healthy volunteers are asked to make up to two onsite visits to MGH over the course of approximately two months. At these visits, participants will undergo an MRI scan to enable researchers to look at structural changes in the brain. Participants will also have blood drawn for analysis of inflammatory markers and generation of stem cells for further research. Other outcome assessments for ALS participants include breathing tests, muscle tests, and questionnaires, as well as an optional lumbar puncture to enable researchers to analyze biomarkers in the CSF. Finally, a subset of participants will undergo PET scans, which allow researchers to identify regions of inflammation in the brain.

Participants must be between the ages of 18 and 80, be medically safe to undergo an MRI scan (i.e., no metallic particles in the body), and be able to safely lie flat for at least 90 minutes. Additionally, participants cannot be taking any immunosuppressive medications or have a diaphragm pacing system and cannot have a diagnosis of Parkinson’s disease, Alzheimer’s disease, unstable psychiatric disease, cognitive impairment, or renal failure.

Principal Investigators: Nazem Atassi, MD, MMSc, and Suma Babu, MD, MPH

Sponsors: ALS Association and Philanthropy

Enrollment Contact

Olivia Pijanowski
617-643-2522
opijanowski@mgh.harvard.edu

Jianing Liu
617-726-1180
Jliu45@mgh.harvard.edu

Catherine Cebulla
617-643-6252
ccebulla@mgh.harvard.edu

Clinical Trials 101

What is a Clinical Trial, and Why are they Necessary for ALS?

Clinical trials are important to test the safety and effectiveness of new treatments for Lou Gehrig's disease (ALS). Learn more about the different stages of ALS clinical trials below.

Darlene Sawicki, NP and Willam David, MD from the ALS Multidisciplinary Clinic in the Healey Center for ALS at Mass General.

If you or a loved one has ALS, you know the heartbreaking frustration that there are not yet treatments that can stop or significantly slow the disease. You may not know that there are hundreds of scientists and doctors working hard to discover those treatments. That discovery depends, in large part, on the willing spirit of people with ALS who volunteer to be a part of a clinical trial.

The search for new therapies usually begins in the laboratory, where ideas for new treatments are tested in cell cultures or animal models. These steps are critical for showing whether a potential treatment has any merit at all. A treatment that fails in the lab is put aside. But one that succeeds there must still be tested in the most important arena of all, the clinical trial.

A clinical trial is the best way researchers have developed to find effective treatments, and, equally importantly, to weed out useless or harmful ones. Clinical trials are costly, and may last months. When the treatment being tested proves to not be effective, it can be sorely disappointing. But clinical trials have proven to be the most reliable way, and ultimately the fastest way, to discover treatments that really work.

In fact, there are several types of clinical trials, each of which is important to test both the safety and effectiveness of the new treatment, such as a drug for ALS.

Phase I trial

The drug is given to a small number of people, either healthy volunteers or people with ALS, to see if it is safe in humans. The numbers are kept small in order to expose as few people as possible to an untried treatment. In fact, by the time a Phase I study begins, researchers have a great deal of confidence that the drug is likely to be quite safe, based on their results from other experiments; nonetheless, the Phase I trial is critical to determine safety. A Phase I trial may also begin to test whether the drug is effective in treating ALS, but this is not its main purpose, and any positive results can only be considered tentative.

Phase II trial

A drug that is safe can be initially tested for effectiveness in a Phase II trial. This trial typically enrolls between 30 and 50 people with ALS. Most Phase II trials test the drug against a placebo—an identical pill (or injection, or other form of delivery) that does not contain the drug (this is called a placebo-controlled trial). Neither the researcher nor the ALS patient knows which is which. In this way, their hope of benefit from the real treatment will not affect the results. If the drug continues to appear safe, and shows some signs of effectiveness, it will be tested in the next phase, Phase III.

Phase III trial

A phase III trial is considered the definitive test of whether a drug is effective. It is always a placebo-controlled trial, and enrolls many more patients than a phase II trial. It is usually conducted by multiple researchers at multiple different sites around the country or even around the world. A treatment that succeeds in a Phase III trial is considered to be truly effective. Once a successful trial is over, the company that manufactures the drug can apply to the United States Food and Drug Administration (FDA) for permission to market the drug for treatment of ALS.

The urgent need for new treatment for ALS can only be met when researchers and people with ALS work together. ALS researchers know that most ALS patients would like to help them develop new treatments. But they also understand the concerns that may make patients and families hesitant to enroll in a trial. Researchers are striving to shorten clinical trials, and make them more convenient for patients and families to take part in.

To learn more about clinical trials, read on about the vital importance of placebo-controlled trials, and about how you can get involved in a clinical trial in your area.

Volunteering for an ALS trial is a big decision. Staff at Mass General can help answer your questions.

Volunteering for an ALS trial is a big decision. Staff at Mass General can help answer your questions.

Getting Involved in a Clinical Trial

Clinical trials are the only way to develop new treatments for people with ALS. People with ALS who enroll in a clinical trial are contributing to improved healthcare for everyone with the disease. Even when the results of a trial are negative, we learn that much more about the disease, and how to look for more promising new treatments.

How do I find out about clinical trials?

Search the clinicaltrials.gov website. This website is a central database of virtually all clinical trials in the United States, and even contains information from other countries. The site is easy to search, and will provide you detailed information about trials in ALS, to help you find trials that may be right for you.

Ask your doctor and ALS study team. They may be able to tell you about new trials starting in your treatment center, or nearby.

How do I know which trial I would qualify for, and which is right for me?

Not every ALS trial is right for every person with ALS. Each trial listed will have information on eligibility that indicates who might be appropriate for the trial.

The eligibility information includes inclusion criteria—characteristics a participant must have—such as a specific age range, disease duration, or subtype of ALS.

Eligibility information also includes exclusion criteria—characteristics that make someone ineligible for enrollment—such as other illnesses or other drug treatments.

Other information you may want to consider are the location of trial centers, the duration of the trial, and any requirements or restrictions that affect you. These are listed in the description of the trial.

Will a trial prevent me from activities or other treatments I value?

The inclusion and exclusion criteria differ for each trial. Some trials exclude people who are taking medications for other illnesses, such as hypertension or diabetes. Some trials exclude people with ALS who are taking other investigational treatments for ALS. In both cases, it would be inappropriate or dangerous to be enrolled in the trial.

In most cases, the person with ALS will continue to receive exactly the same treatments and care as usual, and the investigational treatment will just be added on. Researchers are committed to maintaining the highest level of treatment of all people enrolled in a clinical trial.

How much of a commitment is participation in a clinical trials?

Trials vary greatly in the amount of effort they require from participants. Some trials, especially with drugs known to be safe, won’t require you to visit the trial site much more often than your normal clinical care requires. Sometimes, trial activities can be performed over the phone. Other trials require more frequent monitoring to maximize safety.

The experimental drug may be something you can take by mouth, or might be administered by injection or infusion into your bloodstream. These differences will change both the risks of a trial and the amount of time and effort required of you. When you discuss a trial with people performing it, they should be very clear about these issues. If you are still uncertain after a trial is described to you, keep asking questions.

Does it cost me anything to enter a trial?

There should not be any cost to the participant to enroll in a clinical trial in ALS, either for the treatment itself, or for the medical examinations that are part of the trial. If you need to travel to reach the treatment center, you may have to pay for that, although many trials include funds to help participants defray these costs. The trial contact personnel can tell you more about that for each specific trial.

If I enter a trial, can I drop out of it before the end?

Yes. You may always drop out at any time, for any reason. However, trials produce better information if people stay involved until the end of the trial, so you should not begin a trial unless you plan to complete it.

If you do need to drop out, be sure to inform the doctor who is treating you before you do so. There are some drugs that are not safe to stop all at once, but should be tapered off gradually. It is also valuable to the research team to know who has dropped out, when, and why.

Will I learn the results of the trial, and whether or not I was on placebo?

At the end of any trial, the results are analyzed and then made public. Trial participants are informed of all results, as well as whether they were taking the active drug or the placebo.

What is informed consent, and why is it important?

When you give “informed consent” to be involved in a trial, it means you are agreeing to participate after learning about the potential risks and benefits of your involvement, along with your rights and responsibilities. Members of the research team will explain these to you, and ask you to sign a document indicating you understand what they have said, and are giving your informed consent to be involved. Before you sign, be sure to ask as many questions as you need to fully understand the trial and your involvement in it.

How do I enroll in a clinical trial?

Once you’ve identified a trial you may be interested in, read the detailed information about it on the clinicaltrials.gov site. If you have questions, talk with your doctor, or with the study personnel. If you think the study is right for you, contact the study personnel and let them know. You’ll find contact information on clinicaltrials.gov for each study that is currently recruiting new patients.

Search clinicaltrials.gov.

Placebo Trials

Placebo-controlled trials

Its important to fully understand the structure
of a clinical trial before you volunteer to enroll.

Most ALS patients and caregivers want to do everything they can to help find new treatments for the disease. The idea of trying an experimental therapy is often regarded positively, despite knowing that risks may be present. However, some people have misgivings when they learn that some participants in a trial may receive a placebo rather than the drug being tested. Every ALS researcher has been asked the very reasonable question, why use placebos in a trial for a disease as serious as ALS?

First, some definitionsA placebo is an inactive substance that looks and tastes like the drug being tested but has no effect on the disease the new drug is intended to treat: in this case, ALS. A placebo is sometimes called a sugar pill, or dummy.

The active treatment is the drug or other form of treatment that researchers are testing to see if it will help ALS patients.

A placebo-controlled trial is a trial in which there are two (or more) groups. One group gets the active treatment, the other gets the placebo. Everything else is held the same between the two groups, so that any difference in their outcome can be attributed to the active treatment.

In a double-blind trial, neither the researchers nor the research participants know who is getting active medication and who is getting placebo. A monitoring group not involved in the study randomly assigns patients to one group or the other, and keeps track of the group assignments during the trial. At the end of the trial, the “blind is broken,” and the researchers and patients find out who received active treatment.

In contrast, in an open-label trial, both researchers and patients know the patient is receiving an active treatment.

The placebo effect refers to the tendency all of us have to feel better for a while when we think we are receiving a treatment that will help us. The placebo effect can occur when the treatment is actually helping, or when it is doing nothing, or when it is actually harming us.

So, why use placebos in a trial for a disease as serious as ALS?The double-blind, placebo-controlled trial is considered the “gold standard” for clinical trials, because it has the best chance of determining whether an active treatment is effective. This is true for several important reasons:

  • Because no one knows if they are receiving active treatment, the chances are reduced that any benefit seen will be due to the placebo effect.
  • People with ALS  are a diverse group. One important way in which they differ is in the speed of progression of their illness: some people progress slowly, while others, unfortunately, progress more quickly. By randomly assigning subjects to active treatment and placebo groups, that diversity is spread equally between the groups. This increases the chances that any benefit seen will be due to differences in treatment, rather than differences in the the patients in each group.

The fastest way to develop new treatments for all people with ALS, is to test new drugs in studies designed to give the answer quickly and without doubt. Currently, this is only possible by comparing the active treatment (new therapy) with a placebo.

Two recent ALS clinical trials show how important double-blind, placebo-controlled trials are in weeding out ineffective treatments.

  • An open-label trial of lithium in a small number of patients suggested this drug helped slow the disease. But a larger, placebo-controlled, double-blind trial found no effect. Without that trial, many ALS patients may have gone on to take a useless medication.
  • Animal studies and open-label human trials suggested the antibiotic minocycline was beneficial. But a larger, placebo-controlled trial showed it was not, and may even have been harmful. Without that larger trial, patients may have continued taking minocycline, causing harmful effects without helping their disease.

Only with placebo-controlled trials could these two treatments be ruled out as ineffective in ALS, saving patients from taking medicines that offer no benefit and that could even be dangerous.

An important point to remember is that experimental drugs are indeed experimental. That means that the drug can have a positive effect, no effect at all, or be detrimental. It is sometimes difficult to keep in mind that a patient on a placebo may actually be getting better treatment than someone on the active medication.

A trial with a negative result is very disappointing to both participants and study organizers. But every trial teaches us something valuable and makes subsequent trials more likely to succeed. The disappointment of negative trial results such as these only strengthens our commitment to finding truly beneficial treatments for ALS. That work can only succeed if patients enroll in clinical trials.

If I enter the placebo arm, can I get the active drug later?Yes, if the treatment does provide benefit. We work with the drug companies that supply the treatment for the trial to make sure that if the treatment does prove to be useful, anyone in the trial can continue to receive it after the trial. We feel this is critical to offer treatment to those who have contributed so much to the research by joining the trial.

How can clinical trials be made shorter?A common complaint in ALS trials is that they take too long. We share that concern, and are working to make sure that all trials are completed in the shortest time possible.

Biomarkers: We are looking for new measures of disease progression that are more sensitive to treatment effects, and less susceptible to the daily fluctuations in function that every ALS patient is familiar with. These new measures, called biomarkers, may shorten future trials.

Larger Trials: One major factor in determining the length of a trial is the number of patients enrolled in it. When more patients are enrolled, beneficial effects are seen sooner. This is because different patients naturally progress in their disease at different rates. Those natural differences may temporarily mask any differences in the rate of progression due to a treatment. But with large numbers of patients in each group, those natural differences cancel out sooner, so that even small differences due to treatment emerge quickly.

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