Memantine (10mg BID) for the Frontal and Temporal Subtypes of Frontotemporal Dementia

October 26, 2020 updated by: University of California, San Francisco

A Prospective, Randomized, Multi-Center, Double-Blind, 26 Week, Placebo-Controlled Trial of Memantine (10mg BID) for the Frontal and Temporal Subtypes of Frontotemporal Dementia

The primary objective of the study is to determine whether memantine is effective in slowing the rate of behavioral decline in frontotemporal dementia.

The secondary objective of the study is to assess the safety and tolerability of long-term treatment with memantine in patients with frontotemporal dementia (FTD) or semantic dementia (SD). To determine whether memantine is effective in slowing the rate of cognitive decline in frontotemporal dementia. To evaluate whether memantine delays or decreases the emergence of parkinsonism in frontotemporal dementia.

The tertiary objective of the study is to determine whether treatment with memantine affects changes in weight

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a multicenter, randomized, double-blind, placebo-controlled trial of memantine 10 mg twice daily versus placebo, at a ratio of 1:1, to receive active drug or placebo. Screening and enrollment is planned to last approximately one year. A Data and Safety Monitoring Board, consisting of a clinical pharmacist and 3 neurologists will review all AE reports approximately every 3 months after study initiation. The DSMB will notify the principal investigator, the study sponsor and the CHR if significant concerns are raised by their review of the AE data. An interim analysis of efficacy data will be conducted after 50% of the targeted enrollment population has completed 26 weeks of drug treatment.

Including screening and off-drug follow up, each subject will participate in the study for approximately 34 weeks.

The entire study is anticipated to last 86 weeks if enrollment is completed within one year of study initiation.

The targeted enrollment is 140.

Study Type

Interventional

Enrollment (Actual)

81

Phase

  • Phase 4

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

  • United States
    • California
      • Los Angeles, California, United States, 90095
        • University of California, Los Angeles
      • San Francisco, California, United States, 94143-1207
        • University California, San Francisco
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Mayo Clinic - Jacksonville
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University
    • Maryland
      • Baltimore, Maryland, United States, 21205
        • Johns Hopkins Hospital
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic - Rochester
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599-7025
        • University of North Carolina At Chapel Hill
    • Ohio
      • Cleveland, Ohio, United States, 44120
        • University Hospitals of Cleveland / Case Medical Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104-4283
        • University of Pennsylvania

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

40 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

A subject must meet ALL of the following criteria to be considered for enrollment in this study:

  1. Signed and dated written informed consent obtained from the subject and the subject's caregiver in accordance with local IRB regulations.
  2. Must meet criteria Neary et al. criteria for frontotemporal dementia (FTD) or semantic dementia (SD)
  3. Age: 40-80
  4. CT or MRI of brain within 12 months consistent with a diagnosis of FTD or SD.
  5. MMSE ≥ 15 at screening visit.
  6. Judged by investigator to be able to comply with neuropsychological evaluation at baseline.
  7. Must have reliable caregiver accompany subject to all study visits. Caregiver must read, understand and speak English fluently in order to ensure comprehension of informed consent form and informant-based assessments of subject. Caregiver must also have frequent contact with subject (at least 3 times per week for one hour) and be willing to monitor study medication compliance and the subject's health and concomitant medications throughout the study.
  8. In the opinion of the investigator, the patient and the caregiver will be compliant with the protocol and have a high probability of completing the study.

Exclusion Criteria:

Any one of the following will exclude a subject from being enrolled into the study:

  1. Insufficient fluency in English to complete neuropsychological and functional assessments.
  2. Concurrent Motor Neuron Disease judged by investigator to have bulbar or upper extremity impairments at baseline that would interfere with neuropsychological assessment, or that are expected to lead to such impairments within one month.
  3. Exclusion criteria as listed in Neary criteria. Diagnosis of progressive nonfluent aphasia by Neary criteria.
  4. Use of memantine within 4 weeks prior to randomization.
  5. Evidence of other neurological or psychiatric disorders which preclude diagnosis of FTD (including, but not limited to, stroke, Parkinson's disease, any psychotic disorder, severe bipolar or unipolar depression, seizure disorder, or head injury with loss of consciousness) within the past year.
  6. Concurrent treatment with acetylcholinesterase inhibitors, antipsychotic agents, mood stabilizers (valproate or lithium) or benzodiazepines (other than temazepam or zolpidem), or use of any of these agents within 4 weeks prior to randomization. Atypical antipsychotic agents may be started after the baseline visit if felt to be medically necessary by the investigator and will be recorded as a secondary outcome measure.
  7. History of alcohol or substance abuse within 1 year prior to screening, if deemed clinically significant by investigator.
  8. Any current malignancy, or any clinically significant hematological, endocrine, cardiovascular, renal, hepatic, gastrointestinal or neurological disease. If the condition has been stable for at least the past year and is judged by the investigator not to interfere with the patient's participation in the study, the patient may be included.
  9. Clinically significant lab abnormalities at screening, including Creatinine ≥ 1.7, B12 below laboratory normal reference range or TSH above site's laboratory normal reference range. Subjects with abnormal B12 or TSH levels at screening may be included per investigator's discretion.

9. CT or MRI evidence of any of the following: hydrocephalus, stroke, space-occupying lesion, cerebral infection or any clinically significant CNS disease other than FTD.

10.Systolic blood pressure greater than 180 or less than 90 mm Hg. Diastolic blood pressure greater than 105 or less than 50 mm Hg.

11. Abnormal ECG at screening judged to be clinically significant by the investigator.

12. Use of investigational drugs or participation in investigational drug study within 60 days of screening.

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: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1
Memantine 10mg BID
Drug: memantine
memantine 10mg BID
Placebo Comparator: 2
Placebo condition
Drug: Placebo pill
Placebo pill BID

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Neuropsychiatric Inventory (NPI)
Time Frame: Baseline, 26 weeks
NPI:12-domain caregiver assessment of behavioral disturbances occurring in dementia: delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, motor disturbance, appetite/eating, nighttime behavior. A screening question is asked about each sub-domain. If the responses to these questions indicate that the patient has problems with a particular sub-domain of behavior, the caregiver is only then asked all the questions about that domain, rating the frequency of the symptoms on a 4-point scale, their severity on a 3-point scale, and the distress the symptom causes them on a 5-point scale. Severity(1=Mild to 3=Severe),frequency(1=occasionally to 4=very frequently) scales recorded for each domain; frequency*severity=each domain score(range 0-12). Total score=sum of each domain score(range 0-144);higher score=greater behavioral disturbances;negative change score from baseline=improvement.
Baseline, 26 weeks
Clinical Global Impression of Change (CGIC)
Time Frame: 26 Weeks
The scale is rated on a 7-point scale, using a range of responses from 1 (very much improved) through 7 (very much worse). The clinician compares the participant's current condition to the condition at admission to the project.
26 Weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Longitudinal Changes From Baseline to 26 Weeks for Test Battery: CDR-SB, FAQ, TFLS, MMSE, EXIT25, UPDRS, Boston Naming Test
Time Frame: Baseline and 26 Weeks

Clinical dementia rating sum of boxes CDR-SB (0-18) high scores indicate high impairment.

Functional activities questionnaire FAQ (0-30) high scores indicate high impairment.

Texas functional living scale TFLS (0 to 52) high scores suggest better instrumental activities of daily living functioning.

Mini-Mental State Examination MMSE (0-30) low scores indicate low cognition. The executive interview EXIT25 (0 to 50) high scores indicate more executive impairment.

A modified unified Parkinson's disease rating scale UPDRS (0-199) high scores indicate worse disability.

Boston naming test (0-15) low scores indicate more retrieval difficulties.
Baseline and 26 Weeks
Longitudinal Changes From Baseline to 26 Weeks for Test Battery: Letter Fluency, Category Fluency, Digit Symbol, Digits Backwards
Time Frame: Baseline and 26 Weeks

Letter fluency, score is number of words recalled starting with a specified letter for 60 seconds. There are 3 trials, with 3 different letters. The total number of correct responses is totaled for all 3 trials for the score. Low scores indicate high impairment

Category fluency, score is number of items generated belonging to a specific category (such as animals) in 60 seconds, low scores indicate high impairment.

Digit symbol, score is number of symbols that correctly corresponded to the random numerals entered in the form in 90 seconds. Participants are given a table of numerals with matching symbols, and a form with random numerals with open spaces. Low scores indicate high impairment.

Digits backwards, score is number of digits backwards recalled (range: 0-14), The participant hears a list of digits and is asked to repeat the digits backwards. Low scores indicate high impairment.
Baseline and 26 Weeks
Number of Participants Starting Antipsychotic Therapy
Time Frame: 26 weeks
26 weeks

Collaborators and Investigators

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

Sponsor

University of California, San Francisco

Collaborators

Forest Laboratories

Investigators

  • Principal Investigator: Adam L. Boxer, M.D., Ph.D., University of California, San Francisco
  • Principal Investigator: Bruce Miller, M.D., University of California, San Francisco

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.

General Publications

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

October 1, 2007

Primary Completion (Actual)

December 1, 2012

Study Completion (Actual)

December 1, 2012

Study Registration Dates

First Submitted

October 16, 2007

First Submitted That Met QC Criteria

October 17, 2007

First Posted (Estimate)

October 18, 2007

Study Record Updates

Last Update Posted (Actual)

November 17, 2020

Last Update Submitted That Met QC Criteria

October 26, 2020

Last Verified

October 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NAM-53:memantineplacebo

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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