Trial record 2 of 76 for:    FRONTOTEMPORAL DEMENTIA

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

This study has been completed.
Sponsor:
Collaborator:
Forest Laboratories
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT00545974
First received: October 16, 2007
Last updated: December 13, 2013
Last verified: December 2013
  Purpose

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


Condition Intervention Phase
Frontal Lobe Dementia
Frontotemporal Lobe Dementia
Semantic Dementia
Drug: memantine
Drug: Placebo pill
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Change in Neuropsychiatric Inventory (NPI) [ Time Frame: Baseline, 26 weeks ] [ Designated as safety issue: No ]
    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.

  • Clinical Global Impression of Change (CGIC) [ Time Frame: 26 Weeks ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • CDR-FTD, MMSE, FAQ, TFLS, EXIT25, UCSF FTD-Neuropsychological Test Battery: CVLT, Verbal Fluency, Modified BNT, Backward Digit Span, Digit Symbol Test, Modified Trails B, Modified Unified Parkinson's Disease Rating Scale, Antipsychotic Therapy [ Time Frame: 26 Weeks ] [ Designated as safety issue: No ]

Enrollment: 81
Study Start Date: October 2007
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Memantine 10mg BID
Drug: memantine
memantine 10mg BID
Placebo Comparator: 2
Placebo condition
Drug: Placebo pill
Placebo pill BID

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.

  Eligibility

Ages Eligible for Study:   40 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00545974

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

Additional Information:
Publications:
Boxer AL, Trojanowski JQ, Lee VY-M, Miller BL (2005) Frontotemporal Lobar Degeneration. In: Neurodegenerative Diseases: Neurobiology, Pathogenesis and Therapeutics (Beal MF, Lang AE, Ludolph AC, eds), pp 481 - 493. Cambridge, UK: Cambridge University Press.

Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT00545974     History of Changes
Other Study ID Numbers: NAM-53:memantineplacebo
Study First Received: October 16, 2007
Results First Received: April 22, 2013
Last Updated: December 13, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of California, San Francisco:
Frontotemporal Dementia
Semantic Dementia
dementia
Dementia
Randomized
Double-Blind
Placebo-Controlled
memantine
Namenda
FTD
ftd
SD
sd
behavioral decline
cognitive decline

Additional relevant MeSH terms:
Dementia
Frontotemporal Dementia
Pick Disease of the Brain
Delirium, Dementia, Amnestic, Cognitive Disorders
Frontotemporal Lobar Degeneration
Aphasia, Primary Progressive
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Mental Disorders
TDP-43 Proteinopathies
Neurodegenerative Diseases
Proteostasis Deficiencies
Metabolic Diseases
Aphasia
Speech Disorders
Language Disorders
Communication Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Signs and Symptoms
Memantine
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Antiparkinson Agents

ClinicalTrials.gov processed this record on July 24, 2014