Down Syndrome Memantine Follow-up Study
Condition: Down Syndrome; Intellectual Disability
MeSH terms: Down Syndrome; Intellectual Disability; Syndrome
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this research study is to learn if the medication Memantine Hydrochloride (the
      study medication) can help adolescents and young adults with Down syndrome. Dr. Alberto Costa
      and his research team want to see if a 16-week treatment with this medication can improve the
      participant's ability to learn and remember things. In this study, memantine hydrochloride
      will be used. Thus, the researchers want to learn whether the study drug can help improve
      memory in young adults with Down syndrome. To test the effect of the study medicine, half of
      the people in the study will receive the study medicine and half will receive a placebo (an
      inactive substance). Memantine is an approved medication to treat memory and thinking
      problems in persons with Alzheimer disease. However, little is known about the effect of this
      medication in persons with Down syndrome and it has not been approved for use in persons with
      Down syndrome.
    

Detailed description: 
      This study seeks to investigate if the medication Memantine Hydrochloride can help young
      adults with Down syndrome. Two hundred persons with Down syndrome from both genders and
      between 15 and 32 years of age will be recruited from two sites: Cleveland, OH, USA and São
      Paulo, SP, Brazil. Participants will be assigned randomly to either a placebo group or a
      group taking the active medication with a 50% probability of being on either group. Neither
      the participants nor the investigators will know who will be taking the study medication and
      who will be taking the placebo during the study. Only the investigational pharmacist will
      have access to this information.

      Up to 60 people with Down syndrome of the recruited study participants will take part on an
      optional magnetic resonance imaging (MRI) study. This investigation is aimed at helping to
      make the EEG study more precise and to find out whether the study medication has any
      significant effect on the structure of the brain.

      Additionally, we will recruit a control group of 60 age- and gender-matched participants
      without Down syndrome. The goal is to investigate how different groups of people activate
      their brains when they hear or see something, and if he can use high-density EEG and MRI to
      see how this study medication works in persons with Down syndrome. In other words, this
      additional control group should help us ascertain which parts of the test results are due to
      a person having Down syndrome and which ones are not. Persons without Down syndrome will only
      come for one EEG visit and one MRI visit, and not be asked to take the study medication.

      The visits for the participants with Down syndrome will be as follows:

      Screening visit (approximately 2-hour long). The subject will be asked about his/her health,
      medical history, social background, and work background, as well as some simple questions to
      determine performance on tests of memory and function that are part of this study. Informed
      consent and assent will be obtained in this visit. At the end of this visit, an EEG machine
      will be used to access brain responses to different auditory and visual stimuli. Some will be
      asked if they would be willing to have an MRI performed, but this portion is not imperative.

      A urine sample will be collected and used to obtain cells that will be kept frozen for
      potential future studies. If the date of the screening visit is not convenient, this sample
      can be collected during any of the next five visits.

      Visit 1 (approximately 1 hour). Pulse, blood pressure, and an electrocardiogram (ECG) will be
      taken. At the end of the visit, urine and blood samples will be taken. Pregnancy will also be
      checked.

      Visit 2 (2-3 hours). Tests of memory, learning, and reasoning skills will be conducted before
      the start of the study medicine or placebo. At the end of this visit, a 60-day supply of
      either the study medicine or the placebo will be given. This will need to be taken for 16
      weeks.

      Visit 3 (approximately 30 minutes). Eight weeks after the beginning of the treatment, the
      participant will return to assess how she/he is doing under the treatment. Pulse, blood
      pressure, a physical exam, and pregnancy will be checked. At this visit, another supply of
      study medicine will be given.

      Visit 4 (2-3 hours). Sixteen weeks after starting the medicine, the participant will take a
      second series of tests in learning, memory, and reasoning skills to find out whether there
      were any changes in these skills.

      Visit 5 (approximately 1 hour). In the 16th or 17th week after starting the medicine, the
      participant will meet one more time with the doctor from visits 1 and 3. Vital signs, a
      physical exam, and an ECG will be taken, as well as a blood sample to ensure nothing has
      changed with the participant's general health. For women, a pregnancy test will be performed.

      If for some reason the subject withdraws from this study prior to Visit 5, he/she will be
      asked to return to the clinic for a "Treatment Discontinuation Visit." In addition, if the
      participant discontinues the medication prior to the end of the study, he/she will be asked
      to complete a "Retrieved Dropout Visit" on the date that should have represented Visit 5.
      Study medication will not be provided beyond the study period.
    

Intervention name(s): Memantine; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Encapsulated Namenda 10 mg bid (after four-week standard dose titration protocol); Identically looking placebo capsules bid (after a four-week regimen designed to mimic standard dose titration protocol)
Other intervention name(s): Namenda; Inactive Capsules
Intervention MeSH terms: Memantine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Memantine; Episodic Memory; CVLT; Hippocampus dependent memory; Short-term memory