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

NCT01112683 | Completed Phase 4 Results DMC

• 1 other identifier: 06-0934
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Down Syndrome

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)

Outcome Measures

Primary Outcomes (1)

• Changes in Neuropsychological Measures From Baseline to End of Study

  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

  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

Secondary Outcomes (2)

• Changes in Benchmark Neuropsychological Measures From Baseline to End of Study

  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

• Changes of Safety and Tolerability Assessments at Baseline and End of Study

  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

Study Arms (2)

Memantine

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

These are identically-looking pills to the ones in the Memantine Arm

Drug: Placebo

Interventions

Memantine DRUG

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).

Also known as: Memantine brand name in the USA is Namenda

Memantine

Placebo DRUG

These are identically-looking pills to those in the Memantine Arm.

Also known as: Sugar Pills

Placebo

Eligibility Criteria

• Age: 18 Years - 32 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Colorado, Denver: lead
• Forest Laboratories: collaborator

Study Sites (1)

The Children's Hospital

Aurora, Colorado, 80045, United States

Location

Related Publications (1)

• Boada R, Hutaff-Lee C, Schrader A, Weitzenkamp D, Benke TA, Goldson EJ, Costa AC. Antagonism of NMDA receptors as a potential treatment for Down syndrome: a pilot randomized controlled trial. Transl Psychiatry. 2012 Jul 17;2(7):e141. doi: 10.1038/tp.2012.66.

  PMID: 22806212 RESULT

MeSH Terms

Conditions

Down Syndrome

Interventions

Memantine

Condition Hierarchy (Ancestors)

Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn

Intervention Hierarchy (Ancestors)

Amantadine; Adamantane; Bridged-Ring Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Dr. Alberto Costa
• Organization: University of Colorado School of Medicine

Alberto.Costa@ucdenver.edu

303-724-6007

Study Officials

• Alberto Costa, MD, Ph.D

  University of Colorado School of Medicine

  PRINCIPAL INVESTIGATOR

• Edward Goldson, MD

  Children's Hospital Colorado

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2010
• First Posted: April 28, 2010
• Study Start: July 1, 2008
• Primary Completion: July 1, 2011
• Study Completion: August 1, 2011
• Last Updated: February 1, 2013
• Results First Posted: February 1, 2013

Record last verified: 2012-12

Locations

US (1)