Trial of Ginkgo as a Treatment for Cognitive Problems in Multiple Sclerosis
|Multiple Sclerosis Cognitive Ability, General||Drug: Ginkgo biloba Drug: Placebo||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Ginkgo Biloba for Cognitive Impairment in Multiple Sclerosis|
- Primary Outcome is Performance on the Interference Condition of the Stroop, the Long Delay Free Recall Portion of the California Verbal Learning Test II, the 2 Second Paced Auditory Serial Addition Test and the Controlled Oral Word Association Test. [ Time Frame: 12 weeks ]
Performance at exit adjusted for baseline performance on 4 neuropsychological tests:
STROOP(Victoria version):Tests attention&executive function. Outcome is the interference condition condition; time needed to name the colors in which words (which are names of colors) are printed. Words and colors are mismatched.
CaliforniaVerbalLearningTest- II: Tests verbal/learning/memory. Outcome number of words (shopping list) remembered after 20 min delay with no cues.
PacedAuditorySerialAdditionTest:Tests working memory/sustained attention. Outcome is the number of correct responses to recording giving numbers every 2 sec. Last 2 numbers must be added together before the next number.
ControlledOralWordAssociationTest:Tests letter fluency. Outcome number of words produced in one minute for each of 3 letters.
Measures reported as Z-scores based on the available population norms for each test; range -infinite +infinite; 0 average; -1=1std below average; +1=1std above average.
- Secondary Outcome: Measures of Self-report as Well as Family Reports of Subject's Cognitive Deficits and Assessment of Social Integration. [ Time Frame: 12 weeks ]
The Perceived Deficits Questionnaire (PDQ), a standardized questionnaire in which the subject reports on his or her cognitive function; Measure total score Range (0 best - 80 worse) Multiple Sclerosis Neuropsychological Screening Questionnaire (MSNQ), in which the family member who was most aware of the participant's cognitive deficits reports on the subject's cognitive deficits; measure total score range (0 best - 60 worse) 'and the Community Integration Questionnaire (CIQ) in which the subject reports his or her degree of social integration; range (0 worst - 32 best); measure total score.
Sub-scales for these 3 measures were not used for outcome measures only total scores.
|Study Start Date:||January 2009|
|Study Completion Date:||December 2010|
|Primary Completion Date:||November 2010 (Final data collection date for primary outcome measure)|
Active Comparator: Arm 1
Subjects with multiple sclerosis and documented cognitive impairment will be randomized to take the intervention or placebo.
Drug: Ginkgo biloba
120 mg orally twice a day for 12 weeks
Other Name: EGb 761
Placebo Comparator: Arm 2
Subjects with multiple sclerosis and documented cognitive impairment will be randomized to receive the placebo.
One capsule orally twice a day for 12 weeks
Primary objective: Determine the difference between subjects treated with Ginkgo biloba (GB) and subjects treated with placebo for 12 weeks on the performance of a battery of neuropsychological tests that are frequently impaired in Multiple Sclerosis (MS): the Stroop test, the Paced Auditory Serial Addition Test (PASAT), the California Verbal Learning Test (CVLT-II), and the Controlled Oral Word Association Test (COWAT). Secondary objectives: Determine the difference between the two groups after treatment in the following outcomes: 1) incidence of treatment related side effects, 2) cognitive performance as reported by the subjects on the Perceived Deficits Questionnaire, 3) cognitive performance as reported by the subject's family members or caregivers as measured on the Multiple Sclerosis Neuropsychological Screening Questionnaire and 4) community integration as measured with the Community Integration Questionnaire.
This will be a randomized double blind placebo controlled trial of GB 120 mg twice a day for 12 weeks.
One hundred fifty-eight subjects (79 per group) will be randomly assigned to placebo or GB. Subjects will be evaluated at baseline and exit with the cognitive test battery and the self report measures detailed above.
For the primary outcome, multivariate analysis of covariance (MANCOVA) will be used to analyze the changes in all the cognitive tests simultaneously. This analysis will be followed by the analysis of covariance (ANCOVA) for each of the cognitive tests in the battery. The sample size we selected has a power of 0.80 with an alpha level of 0.05 on the overall MANCOVA and for each of the ANCOVA's after Bonferroni's correction.
The self report measures will be analyzed using ANCOVA with baseline responses as covariates.
Safety evaluations will include complete blood count and metabolic panel as well as physical exams at baseline and at exit. The physical exam will include the Expanded Disability Scale (EDSS). Telephone follow-ups will be done monthly while on treatment and one month after exiting the study to review study procedures and assess side effects. Adverse reactions will be classified using the categories and grading in the Cancer Therapy Evaluation Program (CTEP) Common Toxicity Criteria (CTC) Version 3.0 and reported to the Institutional Review Board (IRB) following the institutions guidelines. A Data Safety Management Board (DSMB) will oversee the study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00841321
|United States, Oregon|
|Portland VA Medical Center, Portland, OR|
|Portland, Oregon, United States, 97239|
|United States, Washington|
|VA Puget Sound Health Care System, Seattle|
|Seattle, Washington, United States, 98108|
|Principal Investigator:||Dennis N. Bourdette, MD||Portland VA Medical Center, Portland, OR|