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

NCT00545974 | Completed Phase 4 Results DMC

• 1 other identifier: NAM-53:memantineplacebo
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 9

Brief Summary

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

Conditions

Frontal Lobe Dementia; Frontotemporal Lobe Dementia; Semantic Dementia

Keywords

Randomized; Double-Blind; Placebo-Controlled; memantine; Namenda; Frontotemporal Dementia; Semantic Dementia; FTD; SD; dementia; behavioral decline; cognitive decline

Outcome Measures

Primary Outcomes (2)

• Change in Neuropsychiatric Inventory (NPI)

  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)

  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 Outcomes (3)

• Longitudinal Changes From Baseline to 26 Weeks for Test Battery: CDR-SB, FAQ, TFLS, MMSE, EXIT25, UPDRS, Boston Naming Test

  Baseline and 26 Weeks

• Longitudinal Changes From Baseline to 26 Weeks for Test Battery: Letter Fluency, Category Fluency, Digit Symbol, Digits Backwards

  Baseline and 26 Weeks

• Number of Participants Starting Antipsychotic Therapy

  26 weeks

Study Arms (2)

1

EXPERIMENTAL

Memantine 10mg BID

Drug: memantine

2

PLACEBO COMPARATOR

Placebo condition

Drug: Placebo pill

Interventions

memantine DRUG

memantine 10mg BID

1

Placebo pill DRUG

Placebo pill BID

2

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A subject must meet ALL of the following criteria to be considered for enrollment in this study:
• Signed and dated written informed consent obtained from the subject and the subject's caregiver in accordance with local IRB regulations.
• Must meet criteria Neary et al. criteria for frontotemporal dementia (FTD) or semantic dementia (SD)
• Age: 40-80
• CT or MRI of brain within 12 months consistent with a diagnosis of FTD or SD.
• MMSE ≥ 15 at screening visit.
• Judged by investigator to be able to comply with neuropsychological evaluation at baseline.
• 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.
• 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.

You may not qualify if:

• Any one of the following will exclude a subject from being enrolled into the study:
• Insufficient fluency in English to complete neuropsychological and functional assessments.
• 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.
• Use of memantine within 4 weeks prior to randomization.
• 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.
• 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.
• History of alcohol or substance abuse within 1 year prior to screening, if deemed clinically significant by investigator.
• 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.
• 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.
• \. 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.
• Systolic blood pressure greater than 180 or less than 90 mm Hg. Diastolic blood pressure greater than 105 or less than 50 mm Hg.
• \. Abnormal ECG at screening judged to be clinically significant by the investigator.
• \. Use of investigational drugs or participation in investigational drug study within 60 days of screening.

Sponsors & Collaborators

• University of California, San Francisco: lead
• Forest Laboratories: collaborator

Study Sites (9)

University of California, Los Angeles

Los Angeles, California, 90095, United States

Location

University California, San Francisco

San Francisco, California, 94143-1207, United States

Location

Mayo Clinic - Jacksonville

Jacksonville, Florida, 32224, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21205, United States

Location

Mayo Clinic - Rochester

Rochester, Minnesota, 55905, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599-7025, United States

Location

University Hospitals of Cleveland / Case Medical Center

Cleveland, Ohio, 44120, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104-4283, United States

Location

Related Publications (27)

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  PMID: 23290598 RESULT

Related Links

• UCSF Memory and Aging Center

MeSH Terms

Conditions

Frontotemporal Dementia; Dementia; Cognitive Dysfunction

Interventions

Memantine

Condition Hierarchy (Ancestors)

Frontotemporal Lobar Degeneration; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; TDP-43 Proteinopathies; Neurodegenerative Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

Lower enrollment than planned may have limited ability detect a treatment effect; Small size of semantic dementia group limits generalizability of results to FTD syndrome; Newer tools have been developed to better capture FTD-specific behaviors.

Results Point of Contact

• Title: Dr. Adam L. Boxer
• Organization: UCSF Memory and Aging Center

aboxer@memory.ucsf.edu

4154760668

Study Officials

• Adam L. Boxer, M.D., Ph.D.

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Bruce Miller, M.D.

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• 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: October 16, 2007
• First Posted: October 18, 2007
• Study Start: October 1, 2007
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: November 17, 2020
• Results First Posted: February 5, 2014

Record last verified: 2020-10

Locations

US (9)