Clinical trial NCT02304302
Conditions: Down Syndrome Intellectual Disability
Keywords: Memantine Episodic Memory CVLT Hippocampus dependent memory Short-term memory
Sponsor: University Hospitals Cleveland Medical Center
Start date: 2014-10-01; Completion date: 2020-07-22
Enrollment: 160 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief 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.

Arms: arm 1: Identically-looking placebo pills to memantine will be dispensed in a 66-day supply (56 days plus 10 extra days) by the study coordinator to participants receiving the placebo at the end of visits 2 and 3. arm 2: Memantine will be dispensed in a 66-day supply (56 days plus 10 extra days) by the study coordinator to participants receiving the placebo at the end of visits 2 and 3.
Interventions: intervention 1: Memantine intervention 2: Placebo
Intervention descriptions: intervention 1: Encapsulated Namenda 10 mg bid (after four-week standard dose titration protocol) intervention 2: Identically looking placebo capsules bid (after a four-week regimen designed to mimic standard dose titration protocol)

Protocol documents:
Prot_SAP_000.pdf: 
IRB Administration Offices
UH IRB Phone: 216.844.1529
CWRU IRB Phone: 216.368.6925 
The UH IRB operates under HHS Federalwide Assurance (FWA) number 00003937 and 
IRB registration numbers 00000684, 00001691 and 00008600. The CWRU IRB operates 
under DHHS FWA00004428 and IRB registration number 00000683.
HRP-510
Page 1 of 2
APPROVAL 
Principal Investigator:
Stephen Ruedrich
Title:
Phase II, Multicenter, Sixteen-Week, Randomized, Double 
Blind, Placebo-Controlled Evaluation of the Efficacy, 
Tolerability and Safety of Memantine Hydrochloride on 
Enhancing the Cognitive Abilities of Adolescents and Young 
Adults with Down Syndrome
IRB Number:
06-14-41.
Submission Number:
MODCR00001477
IRB Office:
UH IRB
Approval Date:
6/6/2021
Effective Date:
6/6/2021
Approval End Date:
6/5/2022
Type of Submission:
Modification and Continuing Review
Type of Review:
Expedited
Documents Reviewed:
• Alana-Memantine-High-Density-EEG-MRI-Consent 7-2-
2020.pdf, Category: Consent Form;
• Costa Protocol 7-9-2020, Category: IRB Protocol;
• Alana-Memantine-Assent 1-22-19.pdf, Category: Consent 
Form;
• Informed Consent Chicago 7-2-2020.pdf, Category: 
Consent Form;
• Alana-Memantine-MRI-Consent 7-2-2020.pdf, Category: 
Consent Form;
• Informed Consent 7-2-2020.pdf, Category: Consent Form;
The IRB reviewed this submission.

Per Federal regulation, changes MAY NOT be made to any element of the current 
research without prior IRB approval, except to eliminate an immediate and apparent 
hazard to subjects enrolled in the study.

Per Federal regulation, the research may not continue beyond the Approval End 
date. You must submit a continuing review form 6-8 weeks before this Approval End 
date in order to maintain IRB approval. Failure to maintain IRB approval is human 
subjects non-compliance.  Please note that even if your study falls into a category that 


IRB Administration Offices
UH IRB Phone: 216.844.1529
CWRU IRB Phone: 216.368.6925 
The UH IRB operates under HHS Federalwide Assurance (FWA) number 00003937 and 
IRB registration numbers 00000684, 00001691 and 00008600. The CWRU IRB operates 
under DHHS FWA00004428 and IRB registration number 00000683.
HRP-510
Page 2 of 2
does not require an Approval End date, the institution may require a yearly “check-
in” to confirm the status of the study.  
***Approval by the IRB does NOT mean that you have permission to start your study. 
Prior to starting your study, you may be required to obtain (1) a coverage analysis for 
studies that involve patient care, regardless of source of funding, and/or (2) a contract 
with the Sponsor of your study or an agreement with any third-party collaborator that 
may receive UH or CWRU patient information in any format. Please ensure that all 
required approvals are obtained before initiation of research activity. ***