Roche: Screening Protocol for a Drug that Might Improve Cognitive Capacities in People with Down Syndrome
Q: Why is this research study being done?
A: This is a screening study to identify adults with Down syndrome who are interested and eligible to participate in an upcoming clinical trial, which will primarily evaluate the efficacy, safety, and tolerability of the new drug. The drug holds promise in enhancing the learning, memory, and language abilities in people with Down syndrome.
Q: How long will I take part in the research study?
A: The screening protocol will require one research visit, which may take up to 5 hours. If the adult with Down syndrome is deemed eligible after the screening protocol, they will then be invited to participate in the full clinical trial, which will take place later this year. That clinical trial might take place over a month, involving weekly, or even more frequent, visits to our research center. The visits will be of varying lengths of time.
Q: What does this Screening Protocol involve?
A: Your family member with Down syndrome and one other accompanying family member will need to make one visit to MassGeneral Hospital. Dr. Skotko and the research team will collect the following information during this visit:
- The medical history of the person with Down syndrome, medications that he or she has been taking, and if he or she has had any hospitalizations.
- The person with Down syndrome will have a physical exam, including measurement of height and body weight.
- Blood pressure and pulse rate will be collected.
- An electrocardiogram (EKG) will be performed. This test measures the function of your heart and does not cause any pain to the participant.
- We will ask questions about whether the person with Down syndrome is still in school and/or whether they are working. We’ll ask about their level of education and any other educational programs.
- Our psychologists will administer assessments which measure how well the person with Down syndrome learns, remembers, and speaks.
At the end of this visit, we will analyze the results to determine if the person with Down syndrome is eligible to continue on to the upcoming drug study.
Taking part in this screening study does not automatically guarantee that the person with Down syndrome will be able to take part in the upcoming drug study. This screening study is done to see who qualifies to participate later.
Below is an outline of who is eligible—and who is not—to participate this screening study. These criteria were established by F. Hoffman-LaRoche, the study Sponsor. The person with Down syndrome does NOT need to be an established patient in the MassGeneral Hospital Down Syndrome Program in order to participate in this research opportunity.
Please read through all of these criteria, and if you think you qualify, please call
Mary Ellen McDonough, RN, Senior Clinical Research Coordinator at the MassGeneral Hospital Down Syndrome Program at (617) 643 – 5571 or firstname.lastname@example.org. You may ask her any questions about the study.
Please remember, people will be considered on a first-come/ first-serve basis. At MassGeneral Hospital, we will have up to 33 spots for those who are interested and qualify.
Q: Why is this study on a first-come/first serve basis?
A. The drug company, Roche, has made available a limited number of spots for each site participating in this study. MassGeneral Hospital has the ability to enroll up to 33 subjects in this study. We are screening participants now to determine who will qualify for the drug trial early next year, and eligible patients are screened in the order in which they contact us. By screening participants now, we also have the opportunity to allow certain patients to participate if we anticipate that they will not meet any of the exclusionary criteria by the start of the drug study.
Your family member with Down syndrome must meet ALL of the following requirements to be able to participate in the drug study:
- Males and females, 18-30 years of age.
- Clinical diagnosis of Down syndrome documented with a chromosomal analysis (karyotyping), which includes standard trisomy 21 Down syndrome, isochromosome 21 (also called 21q21q Robertsonian translocation) Down syndrome, Robertsonian translocation Down syndrome, and Down syndrome with reciprocal translocation.
- Ability to complete the testing and evaluation of language and memory.
- Must be willing and assenting or consenting to participant.
- Parent or guardian must be willing to give written informed consent.
- Have a parent or, other reliable caregiver, who will agree to accompany the study participant to the visits during the drug study.
- The parent or caregiver must be a constant and reliable informant with sufficient contact with the study participant to have detailed knowledge of the study participant’s adaptive functioning in order to be able to complete the assessments accurately.
- The person with Down syndrome must be verbal and able to be understood most of the time and must not use other forms of communication, signs, symbol boards, or devices as their primary form of communication.
- The person with Down syndrome should have sufficient vision and hearing to participate in the study-related assessments. This will be based on the clinical judgment of the study doctor.
- The person with Down syndrome taking anti-epileptic medications must have been on a stable dose for at least 4 weeks prior to enrollment in the treatment protocol and that there are no anticipated changes to the ant-epileptic medication dose; withdrawal of anti-epileptic medications; or initiation of additional anti-epileptic medications during the treatment study.
If ANY of the following apply to the person with Down syndrome at this time, he or she would NOT qualify for this study.
- Double aneuploidy of sex chromosomes (e.g., karyotype with 46,X,+21 or 48,XYY,+21)
- Severe lactose intolerance.
- Moderate or severe sleep apnea not well controlled by CPAP.
- History of any malignancy, if not considered likely to be cured.
- History of epilepsy in the last 2 years. Personal history of Infantile Spasms, of Lennox-Gastaut syndrome. Early Infantile Epileptic Encephalopathy or any treatment-refractory epilepsy associated with cognitive or developmental regression, of severe head trauma or Central Nervous System infections (e.g. meningitis), with the exception of a single isolated seizure.
- The person with a known or suspected seizure of any type within 24 months prior to screening. The person with Down syndrome has been seizure-free for 24 months but have required frequent changes of type or dose of anti-epileptic, have consistently had a sub-therapeutic dose levels or who will, in the judgment of the study doctor will require dose alterations, or withdrawal of anti-epileptic medications during the treatment study or are likely to require additional anti-epileptic medication during the treatment study.
- Evidence of unstable digestive, kidney, liver, endocrine, or heart disease.
- Diagnosis of any primary psychiatric diagnosis (including autism spectrum disorder). Problems with intellectual disability, attention deficit hyperactivity disorder, depression, and conduct disorder are allowed as long as they are considered stable and will not interfere with conduct of the drug study.
- History of suicide attempt or deliberate self-harm. During the past 6 months, thinking about suicide or self-harm.
- Personal or family history of congenital long QT syndrome.
- History of HIV or Hepatitis C.
- Pregnant or breast feeding.
- Use of certain medications (see below)
Medications that cannot be taken during this study:
There no restrictions for this screening protocol. However, requirements will apply to the clinical drug trial that will begin later this year. All participants must be on a stable regimen of medications (i.e., a regimen that does not change in the 4 weeks leading up to the beginning of the drug trial) and that the regimen remains unchanged for the duration of the study drug treatment. Long-term use of the following categories of medications will not be permitted during treatment with the study drug:
- Antidepressants other than Serotonin Norepinephrine Reuptake Inhibitors (SNRIs)/Selective Serotonin Reuptake Inhibitors(SSRIs)
- Antipsychotics (treatment with a depot neuoepileptic drug within 6 months of entering the study)
- Hypnotics (melatonin is allowed if the dose is stable)
- Acetylcholinesterase inhibitors
- Other GABAA negative allosteric modulators, (e.g., furosimide)
- GABAA positive allosteric modulators, (e.g,. benzodiazepines for epilepsy)
- Other GABA agonists (e.g., tiagabine, baclofen) or inhibitor of the GABA-transaminase (e.g., vigabatrin)
- Glutamatergic drugs
- Moderate or strong inhibitors of CYP3A4 or P-glycoprotein
- Strong inducers of CYP3A4 or P-glycoprotein