Efficacy and Safety of Memantine Hydrochloride in Enhancing the Cognitive Abilities of Young Adults With Down Syndrome
Condition: Down Syndrome
MeSH terms: Down Syndrome; Syndrome
Intervention: Memantine; Placebo
Intervention description: The drug dosage will follow memantine's standard titration schedule (i.e., 5 mg/d week one, 5 mg/BID week two, 5 & 10 mg/d divided dose week three, 10mg/BID week four).; These are identically-looking pills to those in the Memantine Arm.
Intervention MeSH terms: Memantine
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 42.0
Sex: All
Minimum age: 18 Years
Maximum age: 32 Years
Healthy volunteers: No
Keywords: Down syndrome; Trisomy 21; Pattern Recognition Memory (PRM); Paired Associates Learning (PAL); California Verbal Learning Test (CVLT); Test of Reception of Grammar (TROG-II); Peabody Picture Vocabulary Test (PPVT-III); Scales of Independent Behavior revised (SIB-R)

Summary:

      The purpose of this 16-week research study is to determine whether a drug called memantine
      hydrochloride (memantine) has the potential to help improve memory and other cognitive
      abilities of young adults with Down syndrome (DS). Memantine (Namenda®) is a drug approved by
      the Food and Drug Administration (FDA) for patients with moderate to severe Alzheimer-type
      dementia. About 40 persons of both genders with Down syndrome aged 18-32 years will take part
      in this study. This is a randomized and double blind study. This means that subjects will
      have a 50/50 chance of being assigned to receive either the memantine pills or placebo
      (inactive pills). Neither the study participants nor the research personnel will know who is
      receiving active medication or placebo. Based on memantine's mode of action, current
      knowledge on brain pathology in persons with Down syndrome, and some preclinical data on
      mouse models of Down syndrome, we hypothesize that memantine may improve test scores of young
      adults with Down Syndrome on memory tests targeted at the function of the brain structure
      called the hippocampus. This research project has three specific aims: 1) investigate whether
      memantine has the potential to improve test scores on hippocampus-dependent measures in young
      adults with Down syndrome; 2) investigate whether memantine has the potential to improve test
      scores by these subjects on other cognitive measures; 3) investigate whether memantine is
      well tolerated by these subjects.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Males or females with Down syndrome aged 18 to 32 years. The documented cytogenetic
             diagnosis should be either "Trisomy 21", or "Complete Unbalanced Translocation of the
             Chromosome 21".

          -  Female subjects must be documented not to be pregnant by serum testing at screening.

          -  Laboratory findings within normal limits or judged clinically insignificant at
             baseline.

          -  Vital signs must be within normal limits for their age. (Medically treated hypotension
             will be allowed.)

          -  Screening ECG must demonstrate predominately normal sinus rhythm. Minor abnormalities
             documented as clinically insignificant by the investigator will be allowed. (Subjects
             with clinically significant but stable ECG abnormalities may enter the trial only with
             the permission of the principal investigators.)

          -  Subjects and their authorized representative will provide written informed consent and
             assessment.

          -  Subjects who have been receiving any experimental drug for Down syndrome must undergo
             a washout (~ 30 days or five half-lives of the drug, whichever is longer).

          -  Sufficiently proficient in English to be capable of reliably completing study
             assessments.

          -  Able to swallow oral medication (crushing of tablets will not be permitted).

          -  Must have a reliable caregiver or family member who agrees to accompany the subject to
             all visits, provide information about the subject as required by this protocol, and
             ensure compliance with the medication schedule. The subject must have contact at least
             once a day with the caregiver.

          -  Generally good health and judged by the investigators to be able to fully participate
             in the trial.

        Exclusion Criteria:

          -  Subjects weighing less than 40 kg.

          -  Any current psychiatric or neurologic diagnosis other than Down syndrome.

          -  Subjects who currently meet or have within the past five years met DSM-IV (Diagnostic
             and Statistical Manual) criteria for drug or alcohol abuse or dependence.

          -  Subjects who, in the judgment of the investigators, currently represent a 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.

          -  Subjects who are hospitalized or residing in a skilled nursing facility or subjects
             who are anticipated to enter a nursing home within the next 6 months. (Subjects may
             reside in group homes of other residential settings where they do not require or
             receive skilled nursing.)

          -  Any active or clinically significant conditions affecting absorption, distribution or
             metabolism of the study drugs.

          -  Subjects with significant allergies to or other significant intolerance of memantine
             therapy, its ingredients, or with contraindications to memantine therapy as stated in
             the prescribing information.

          -  Subjects who are expected to require general anesthetics during the course of the
             study.

          -  History or presence of seizure disorder (less than 3 years) or encephalitis.

          -  History of malignant neoplasms treated within 3 years prior to study entry or where
             there is current evidence of recurrent or metastatic disease.

          -  Subjects with treated hypothyroidism must be on a stable dose of medication for at
             least 3 months prior to screening and have normal serum T-4 and thyroid-stimulating
             hormone at screening. Subjects with diabetes mellitus controlled by diet, oral
             medication or insulin must have an HbA1c of < 8.0% and 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.

          -  Subjects who have donated blood or blood products during the 30 days prior to
             screening who plan to donate blood while participating in the study or within four
             weeks after completion of the study.

          -  Subjects who may not be able 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.