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Down Syndrome Memantine Follow-up Study

Information source: University Hospital Case Medical Center
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Down Syndrome; Intellectual Disability

Intervention: Memantine (Drug); Placebo (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: University Hospital Case Medical Center

Official(s) and/or principal investigator(s):
Alberto C Costa, MD, PhD, Principal Investigator, Affiliation: University Hospital Case Medical Center
Stephen L Ruedrich, MD, Study Director, Affiliation: University Hospital Case Medical Center

Overall contact:
Melissa R Stasko, JD, Phone: 216-844-7281, Email: Melissa.Stasko@case.edu


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.

Clinical Details

Official title: Phase II Multicenter 16-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

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: Efficacy of the drug Memantine as assessed by the California Verbal Learning Test-II (CVLT-II) short form

Secondary outcome:

Efficacy of the drug Memantine as assessed by Paired Associates Learning (PAL) from the Cambridge Neuropsychological Test Automated Battery (CANTAB)

Efficacy of the drug Memantine as assessed by Recall of Digits (Differential Ability Scales; DAS-II).

Efficacy of the drug Memantine as assessed by Pattern Recognition Memory (PRM; part of the CANTAB)

Efficacy of the drug Memantine as assessed by Spatial Working Memory (part of the CANTAB)

Efficacy of the drug Memantine as assessed by Spatial Span (part of the CANTAB)

Efficacy of the drug Memantine as assessed by The Go - No Go task

Safety and tolerability of the drug Memantine as assessed by the incidence of adverse events

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.


Minimum age: 15 Years. Maximum age: 32 Years. Gender(s): Both.


Inclusion Criteria:

- Cytogenetically documented Trisomy 21 or Complete Unbalanced Translocation of

Chromosome 21. Mosaic Trisomy 21 and partial translocations will be excluded from the study

- No pregnancy by serum testing at screening. Females of child-bearing potential,

sexually active must be practicing a reliable method of birth control. Urine pregnancy tests will be done at the 2 follow-up medical visits

- Laboratory findings within normal limits or judged clinically insignificant at


- Vital signs within normal limits for age. Stable, medically treated hypotension will

be allowed

- ECG must demonstrate predominately normal sinus rhythm. Minor abnormalities

documented as clinically insignificant will be allowed

- Participants and their authorized representatives will provide written informed


- Participants who have received any experimental drug for Down syndrome must undergo a


- All participants must: Be in general good health as judged by the investigators; Be

able to swallow oral medication; Have a reliable caregiver or family member who agrees to accompany participant to all visits, provide information about the participant as required by the protocol, and ensure compliance with the medication schedule; Be sufficiently proficient in English (USA) or Portuguese (Brazil) to reliably complete the study assessments

- Age and gender matching participants without Down syndrome, must be: Males or females

without Down syndrome aged-matching (within 3 years) participants with Down syndrome whom they are expected to serve as controls Exclusion Criteria:

- Participant weighing less than 40 kg

- Current psychiatric or neurologic diagnosis other than Down syndrome (e. g., major

depressive disorder, schizophrenia, bipolar disorder, autism, Alzheimer disease)

- Current treatment with psychotropic drugs

- Drug or alcohol abuse or dependence

- Significant suicide risk or who would require treatment with electro-convulsive

therapy or with psychotropic drugs during the study or who have received treatment with a depot neuroleptic drug within 6 months of entering the study.

- Current or expected (within the next 6 months) hospitalization or residence in a

skilled nursing facility (may reside in group homes or other residential settings with no skilled nursing)

- Active or clinically significant conditions affecting absorption, distribution, or

metabolism of study drug (e. g. inflammatory bowel disease or celiac disease)

- Significant allergies to or other significant intolerance of memantine therapy, its

ingredients, or with contraindications to memantine therapy as stated in the prescribing information

- Participants who are expected to require general anesthetics during the course of the


- Presence or recent history of seizure disorder (< 3 years).

- Clinically significant and/or clinically unstable systemic disease. (Those with

controlled hypothyroidism must be on a stable dose of medication for at least 3 months prior to screening and have normal serum T-4 and TSH at screening; and those with controlled diabetes mellitus must have an HbA1c of < 8. 0% and a random serum glucose value of < 170 mg/dl)

- Severe infections or a major surgical operation within 3 months prior to screening

- History of persistent cognitive deficits immediately following head trauma.

- Donation of blood or blood products less that 30 days prior to screening, while

participating in the study, or four weeks after completion of the study

- Inability to comply with the protocol or perform the outcomes measures due to

significant hearing or visual impairment or other issues judged relevant by the investigators

- Exclusion criteria for controls without Down syndrome: History of substance abuse,

major psychiatric disorder, attention deficit disorder, or learning disability; Beck Depression Score greater than 10; Exclusion criteria specific to MR scanning; Pregnancy; Neurologic history

Locations and Contacts

Melissa R Stasko, JD, Phone: 216-844-7281, Email: Melissa.Stasko@case.edu

University Hospitals Case Medical Center, Cleveland, Ohio 44106, United States; Recruiting
Melissa R Stasko, JD, Phone: 216-844-7281, Email: Melissa.Stasko@case.edu
Alberto C Costa, MD, PhD, Phone: (216) 844-7395, Email: Alberto.Costa@case.edu
Nancy J Roizen, MD, Sub-Investigator
Hudson G Taylor, PhD, Sub-Investigator
Katherine Koenig, PhD, Sub-Investigator
Richard Boada, PhD, Sub-Investigator

Ibero-American Institute for Research and Care Guidelines in Down Syndrome, São Paulo, SP, Brazil; Not yet recruiting
Zan Mustacchi, MD

Additional Information

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Starting date: October 2014
Last updated: November 25, 2014

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