Research & Clinical Trials

Mass General has a long history of studying ALS. For example, in 1993 Mass General researchers found the first gene that caused a familial form of the disease. Find information on our research studies and enroll in clinical trials.

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  • Neurological Clinical Research Institute

    Neurological Clinical Research Institute

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

Clinical Trials

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 Mass General Clinic.

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 trialThe 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 trialA 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 trialA 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.

Clinical Trial FAQs

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. See our material on navigating clinicaltrials.gov for detailed information that will help you search clinicaltrials.gov.
  • 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

Clinical Trials 101: 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.

ClinicalTrials.gov

Navigating Clinicaltrials.gov

Clinicaltrials.gov is a central database of clinical trials for all conditions, including ALS. It is an important resource for finding a clinical trial that is right for you.  All trials enrolling subjects in the United States, and most trials being conducted worldwide, are listed on this site, so that it is a great place to start searching for what kinds of trials are available.

Here are some helpful tips for searching clinicaltrials.gov:

SEARCHING

  • In the search box, you can put in as many or as few search terms as you wish. You may want to do a very broad search to get started, using “amyotrophic lateral sclerosis” as your only search term. This will bring up the largest number of trials.

Tip: Use “amyotrophic lateral sclerosis” rather than ALS to avoid bringing up non-ALS trials

There are several ways to refine your search:

  • In the original search box, you can put in additional search terms. Use AND to connect them. For instance “amyotrophic lateral sclerosis AND Massachusetts” will return ALS trials taking place in Massachusetts.
  • Go to the "Find Studies" tab and when the drop down menu appears, click on "Advanced Search." Here you can specify many different types of restrictions, including trials that are open (recruiting patients), observational or interventional trials, location, and other criteria.

 

Clinicaltrials.gov Screenshot 1

  • From this page, when you have clicked "search" you will see the "On a Map" tab.  Clicking "On a Map" will show the location of the studies you found on a map.

 

Clinicaltrials.gov Screenshot 2

  • You can click on any region on the world map to find more details. For instance, if you click on the United States, a new map showing state-by-state results appears. You can then click on an individual state to bring up study details.

 

Clinicaltrials.gov Screenshot 3

EXAMPLE:

Let’s say you want to find a trial of a new treatment that is currently recruiting patients in your state Massachusetts for instance). That means you want a trial that is interventional (testing a new treatment) and “open” (currently recruiting patients), that is taking place in Massachusetts.  Your search screen should look like this:

 

Clinicaltrials.gov Screenshot 4

  • Click “Search” to find trials that meet that condition.
  • If you want to expand your search to include additional states, you can do that by including a choice in the “State 2” box.

UNDERSTANDING YOUR SEARCH RESULTS

Your results page lists the trials meeting your search criteria. You can click on each to get further details about the trial. The details may be challenging to understand at first glance. Here are some tips to help you get the most from this information:

  • The best way to begin may be to read the “Detailed Description” about halfway down the page. This provides a discussion of the rationale and design of the trial.
  • Look just below that at the “Eligibility” information. If you meet the inclusion criteria, and are not excluded by the exclusion criteria, you are likely to be eligible for the trial.
  • You can also find information on the page about the primary and secondary “outcome measures.” These are the measurements the researchers will be conducting in the trial.
  • The study location closest to you may be listed on the page, or you may need to click the link “Show [##] Study Locations” to bring up a list of all the locations.

CONTACTING THE STUDY TEAM

Although clinicaltrials.gov is an excellent resource and provides accurate information, important aspects of a trial may not be made clear on the site. For this reason, if you are interested in a study, it is a good idea to discuss it with your ALS physician.

A good next step is to call the study team at the number listed on the website.  Each study site will list the name and location of the institution, the name of the Principal Investigator, and the name and phone number of the person to contact. The “Principal Investigator” (also called the Site Investigator) is the physician who is heading up the study at that location. The contact person is typically the Research Coordinator, who is often a nurse or administrative assistant trained to coordinate clinical trials.

The Research Coordinator takes responsibility for many of the hands-on and day-to-day tasks in conducting the trial, including patient registration, data collection, safety monitoring, and coordination with the site investigator and principal investigator.

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