Efficacy and Safety of Memantine Hydrochloride in Enhancing the Cognitive Abilities of Young Adults With Down Syndrome

This study has been completed.
Sponsor:
Collaborator:
Forest Laboratories
Information provided by (Responsible Party):
University of Colorado, Denver
ClinicalTrials.gov Identifier:
NCT01112683
First received: April 23, 2010
Last updated: December 26, 2012
Last verified: December 2012
  Purpose

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.


Condition Intervention Phase
Down Syndrome
Drug: Memantine
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Sixteen-Week, Randomized, Double Blind, Placebo-Controlled Evaluation of the Efficacy, Tolerability and Safety of Memantine Hydrochloride on Enhancing the Cognitive Abilities of Young Adults With Down Syndrome

Resource links provided by NLM:


Further study details as provided by University of Colorado, Denver:

Primary Outcome Measures:
  • Changes in Neuropsychological Measures From Baseline to End of Study [ Time Frame: These neuropsychological measures will be assessed one time 24 hours before the beginning of treatment and then a second time 16 weeks from the beginning of the treatment ] [ Designated as safety issue: Yes ]

    The hippocampus-dependent measures assessed in the present study are

    1. Pattern recognition memory* - Measures visual memory for non-namable designs; scale range in dataset 4-24; higher score indicates better performance
    2. Paired associates task* - Measures ability to learn visual associations between a picture and its location, and retention of this information over time; scale range in dataset 0-17; higher score indicates better performance
    3. California Verbal Learning Test (CVLT) — Children's Version** - Measures episodic verbal memory (sum of the items recalled over the 4 learning trials); scale range in dataset 0-35; higher score indicates better performance
    4. Rivermead Behavioral Memory Test-Children's version** - Measures episodic memory for visual information presented in context; scale range in dataset 1-20; higher score indicates better performance * used in power analysis calculation of sample size ** secondary measures associated with the primary hypothesis


Secondary Outcome Measures:
  • Changes in Benchmark Neuropsychological Measures From Baseline to End of Study [ Time Frame: Benchmark neuropsychological measures will be assessed one time 24 hours before the beginning of treatment and then a second time 16 weeks from the beginning of the treatment ] [ Designated as safety issue: Yes ]

    The neuropsychological benchmark measures assessed in this study are

    1. Peabody Picture Vocabulary Test-III (PPVT-III; range: -27.00 to 23.00)
    2. Test for the Reception of Grammar (TROG; range: -13.00 to 19.00)
    3. Verbal Fluency (from the Developmental Neuropsychological Assessment (NEPSY); range: -13.00 to 10.00)
    4. Recall of Digits (Differential Ability Scales; DAS; -50.00 to 59.00)
    5. Spatial working memory (SWM; part of the Cambridge Neuropsychological Test Automated Battery, or CANTAB; range: -9.00 to 8.00)
    6. Scales of Independent Behavior Revised (SIB-R; -12.00 to 26.00) All listed values represent differences in scores obtained at baseline subtracted from scores at 16-weeks of treatment. With the exception of the spatial working memory, for all measures, higher values represent better outcome. For the spatial working memory, lower values represent better outcome.

  • Changes of Safety and Tolerability Assessments at Baseline and End of Study [ Time Frame: Safety and tolerability assessments will be performed at three time points: 1) 1-7 days before beginning of treatment; 2) after 8 weeks from the beginning of the treatment; and 3) 16-17 weeks from the beginning of the treatment ] [ Designated as safety issue: Yes ]
    Clinical history and physical examinations, electrocardiograms (ECGs), comprehensive clinical laboratory tests, and incidence of adverse event recording. The comprehensive clinical laboratory tests will include assessments of liver and kidney function, electrolytes, acid/base balance, and blood glucose and proteins. In addition, pregnancy tests will be performed on all female participants of childbearing potential.


Enrollment: 42
Study Start Date: July 2008
Study Completion Date: August 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Memantine
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).
Drug: Memantine
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).
Other Name: Memantine brand name in the USA is Namenda
Placebo Comparator: Placebo
These are identically-looking pills to the ones in the Memantine Arm
Drug: Placebo
These are identically-looking pills to those in the Memantine Arm.
Other Name: Sugar Pills

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 32 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01112683

Locations
United States, Colorado
The Children's Hospital
Aurora, Colorado, United States, 80045
Sponsors and Collaborators
University of Colorado, Denver
Forest Laboratories
Investigators
Principal Investigator: Alberto Costa, MD, Ph.D University of Colorado School of Medicine
Study Director: Edward Goldson, MD Children's Hospital Colorado
  More Information

Publications:
Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT01112683     History of Changes
Other Study ID Numbers: 06-0934, 06-0934
Study First Received: April 23, 2010
Results First Received: July 25, 2012
Last Updated: December 26, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Colorado, Denver:
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)

Additional relevant MeSH terms:
Down Syndrome
Syndrome
Abnormalities, Multiple
Chromosome Disorders
Congenital Abnormalities
Disease
Genetic Diseases, Inborn
Intellectual Disability
Nervous System Diseases
Neurobehavioral Manifestations
Neurologic Manifestations
Pathologic Processes
Memantine
Anti-Dyskinesia Agents
Antiparkinson Agents
Central Nervous System Agents
Dopamine Agents
Excitatory Amino Acid Agents
Excitatory Amino Acid Antagonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014