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

Primary Purpose

Huntington Disease

Status
Completed
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Memantine
Placebo
Sponsored by
University of British Columbia
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Huntington Disease focused on measuring huntington, huntingtin, memantine, ebixa, namenda

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • The Centre for Huntington Disease

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Memantine

Sugar pill

Arm Description

NMDA Receptor Antagonist

Outcomes

Primary Outcome Measures

Utility of TRACK-HD study endpoints in a clinical trial setting
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.

Secondary Outcome Measures

Neuropsychiatric and Cognitive Test Scores
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.

Full Information

First Posted
October 20, 2011
Last Updated
January 9, 2020
Sponsor
University of British Columbia
Collaborators
Huntington Society of Canada, Huntington Study Group
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1. Study Identification

Unique Protocol Identification Number
NCT01458470
Brief Title
A Trial of Memantine as Symptomatic Treatment for Early Huntington Disease
Acronym
MITIGATE-HD
Official Title
A Trial of Memantine as Symptomatic Treatment for Early Huntington Disease; a Phase IIb Study
Study Type
Interventional

2. Study Status

Record Verification Date
January 2020
Overall Recruitment Status
Completed
Study Start Date
September 2011 (undefined)
Primary Completion Date
August 2012 (Actual)
Study Completion Date
November 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of British Columbia
Collaborators
Huntington Society of Canada, Huntington Study Group

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Huntington Disease
Keywords
huntington, huntingtin, memantine, ebixa, namenda

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
19 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Memantine
Arm Type
Active Comparator
Arm Description
NMDA Receptor Antagonist
Arm Title
Sugar pill
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Memantine
Other Intervention Name(s)
Ebixa, DIN 02260638, Namenda
Intervention Description
oral tablet, 1 BID, 24 weeks
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
oral tablet, 1 BID, 24 weeks
Primary Outcome Measure Information:
Title
Utility of TRACK-HD study endpoints in a clinical trial setting
Description
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.
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Neuropsychiatric and Cognitive Test Scores
Description
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.
Time Frame
24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Blair R. Leavitt, MD,CM,FRCPC
Organizational Affiliation
University of British Columbia
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Michael R. Hayden, MD,ChB,PhD
Organizational Affiliation
The University of British Columbia
Official's Role
Study Chair
Facility Information:
Facility Name
The Centre for Huntington Disease
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6T 2B5
Country
Canada

12. IPD Sharing Statement

Links:
URL
http://www.huntington-study-group.org/
Description
The Huntington Study Group
URL
http://www.huntingtonsociety.ca/
Description
The Huntington Society of Canada
URL
http://www.hc-sc.gc.ca
Description
Health Canada

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A Trial of Memantine as Symptomatic Treatment for Early Huntington Disease

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