A Trial of Memantine as Symptomatic Treatment for Early Huntington Disease (MITIGATE-HD)

January 9, 2020 updated by: Blair Leavitt, University of British Columbia

A Trial of Memantine as Symptomatic Treatment for Early Huntington Disease; a Phase IIb Study

Huntington disease is characterized by difficulties in movement and thinking. Psychological disturbances including irritability, aggression, loss of interest, depressed mood, obsessions and compulsions, also represent common symptoms of HD. These symptoms are distressing both for HD patients and their caregivers, contribute to the loss of ability to carry out activities of daily living, and present a major treatment challenge for physicians. The goal of this study is to determine the effect of memantine on movement, thinking and emotional difficulties in HD patients. Memantine is a medication originally approved for the treatment of aggression and agitation in patients with moderate-to-severe Alzheimer's disease (AD), which has also recently been shown to improve the behavioural and neuropathological symptoms in a mouse model of Huntington Disease (HD).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

TRACK-HD was a multi-centre, multi-national, prospective, observational study of pre-manifest and early Huntington's disease (HD) with a control group of volunteers not carrying the HD mutation. The goal of the project was to contribute essential methodology that will form the basis for clinical trials in pre-manifest and early HD. TRACK-HD complemented existing observational studies (e.g., Predict-HD, PHAROS, COHORT), sharing some features, but also having areas of unique emphasis.

The UBC site recruited 90 subjects including 30 control subjects, 30 asymptomatic pre-manifest HD gene carriers and 30 subjects with early symptoms of HD (stage 1 or 2). All subjects were assessed using the TRACK-HD battery at baseline, 1 year, 2 years, and 3 years. Following the fourth visit (3 year assessment), the TRACK-HD study will be completed, and the 30 subjects with early symptoms of HD will be invited to enroll in the MITIGATE-HD Study.

The MITIGATE-HD study is a single center Phase IIb,out-patient,randomized, double-blind, placebo-controlled trial of memantine treatment in subjects with Huntington disease (HD). The study will evaluate Memantine 10 mg two times daily (BID) administered orally (PO) for six months (24 weeks) compared with matching placebo BID. Safety and tolerability will be assessed by recording of adverse events and by monitoring of vital signs, physical examinations, and suicidality risk scores.

The TRACK-HD assessment battery will be administered to all subjects after six months of study drug administration. The effects of memantine will be evaluated both against placebo as well as compared to the previous 3 years of observational data from the TRACK-HD Study.

Study Type

Interventional

Enrollment (Actual)

19

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada, V6T 2B5
        • The Centre for Huntington Disease

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

To be eligible for the study, a subject must be enrolled in the early HD cohort of the TRACK-HD study and:

  • be at least 18 years of age and not older than 65
  • able to provide written consent
  • carry the abnormal HD gene and show early symptoms of HD
  • be able and willing to comply with study requirements, including travel to study center
  • have no metal implants to be suitable for MRI scans and able to tolerate them
  • able to tolerate blood draws
  • be of stable medical, psychiatric and neurological health at the time of enrollment
  • not have a history of significant head injury
  • not have a history of significant hand injury that would prevent either writing or performing rapid computer tasks
  • not be abusing drugs and/or alcohol that may cause failure to comply with study procedures
  • not be currently participating in PREDICT-HD or a clinical drug trial.

Exclusion Criteria:

Prospective subjects will be excluded if:

  • they are younger than 18 years of age and older than 65
  • they are unable to provide written consent
  • they show advanced symptoms of HD if they are HD gene carriers
  • they are unwilling to comply with study requirements, including travel to study center
  • they are unsuitable for MRI (e.g, claustrophobia, metal implants) or unable to tolerate them
  • they are unable to tolerate blood draws; or,
  • they have a major psychiatric disorder, concomitant significant neurological disorder or concomitant significant medical illness at the time of enrollment
  • they have a history of CNS disease or significant head injury; or,
  • they have a history of significant hand injury that would prevent either writing or performing rapid computer tasks; or,
  • they are likely to be non-compliant with study procedures due to drug and/or alcohol abuse; or,
  • they are participating in PREDICT-HD or a clinical drug trial at the time of enrollment.
  • they are not sighted
  • English is not their first language
  • they are currently or treated within the last 6 months with antipsychotic medications, including the traditional neuroleptics such as haloperidol as well as the atypical antipsychotics risperidone, clozapine, quetiapine and olanzapine
  • they are use phenothiazine-derivative antiemetic medications such as prochlorperazine, metoclopramide, promethazine and Inapsine on a regular basis (greater than 3 times per month)
  • they have a history of learning disability and/or mental retardation.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Sugar pill
Other: Placebo
oral tablet, 1 BID, 24 weeks
Active Comparator: Memantine
NMDA Receptor Antagonist
Drug: Memantine
oral tablet, 1 BID, 24 weeks
Other Names:
  • Namenda
  • Ebixa
  • DIN 02260638

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Utility of TRACK-HD study endpoints in a clinical trial setting
Time Frame: 24 weeks
To examine the clinical utility of novel trial endpoints (such as Putaminal NAA measured by MRS) developed in the TRACK-HD study in the setting of a placebo-controlled therapeutic trial.
24 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Neuropsychiatric and Cognitive Test Scores
Time Frame: 24 weeks
To examine effect of memantine versus placebo on the scores of: a) the irritability and agitation/aggression sub-categories of the Neuropsychiatric Inventory (NPI), and also the total NPI, b) cognitive tests: Circle Tracing , Symbol Digit Modality, Stroop Word Reading, and Spot the Change, c) total HD-ADL, d) total UHDRS, and the UHDRS sub-scale: Cognitive, Behavioural, Functional, and Independence scales. e) In patients recruited at the UBC study site, the effect on striatal N-acetyl aspartate levels (a measure of neuronal dysfunction) will be assessed by Magnetic Resonance Spectroscopy.
24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of British Columbia

Collaborators

Huntington Study Group
Huntington Society of Canada

Investigators

  • Principal Investigator: Blair R. Leavitt, MD,CM,FRCPC, University of British Columbia
  • Study Chair: Michael R. Hayden, MD,ChB,PhD, The University of British Columbia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2011

Primary Completion (Actual)

August 1, 2012

Study Completion (Actual)

November 1, 2012

Study Registration Dates

First Submitted

October 20, 2011

First Submitted That Met QC Criteria

October 21, 2011

First Posted (Estimate)

October 24, 2011

Study Record Updates

Last Update Posted (Actual)

January 13, 2020

Last Update Submitted That Met QC Criteria

January 9, 2020

Last Verified

January 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H11-01364

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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