Down Syndrome Memantine Follow-up Study
Condition: Down Syndrome; Intellectual Disability
MeSH terms: Down Syndrome; Intellectual Disability; Syndrome
Intervention: Memantine; Placebo
Intervention description: 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)
Intervention MeSH terms: Memantine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 160.0
Sex: All
Minimum age: 15 Years
Maximum age: 32 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Memantine; Episodic Memory; CVLT; Hippocampus dependent memory; Short-term memory

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.
    

Eligibility criteria:

        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
             baseline

          -  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
             consent

          -  Participants who have received any experimental drug for Down syndrome must undergo a
             washout

          -  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
             study

          -  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