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Trial of Ginkgo as a Treatment for Cognitive Problems in Multiple Sclerosis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT00841321
First received: February 9, 2009
Last updated: May 23, 2014
Last verified: May 2014
  Purpose

The purpose of this study is to see if treatment with Ginkgo improves cognitive function in people with multiple sclerosis who have cognitive problems.


Condition Intervention Phase
Multiple Sclerosis
Cognitive Ability, General
Drug: Ginkgo biloba
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Ginkgo Biloba for Cognitive Impairment in Multiple Sclerosis

Resource links provided by NLM:


Further study details as provided by Department of Veterans Affairs:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

    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:
  • 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 ] [ Designated as safety issue: No ]

    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.



Enrollment: 120
Study Start Date: January 2009
Study Completion Date: December 2010
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: Placebo
One capsule orally twice a day for 12 weeks

Detailed Description:

Objectives:

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.

Research plan:

This will be a randomized double blind placebo controlled trial of GB 120 mg twice a day for 12 weeks.

Methods:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • A diagnosis of multiple sclerosis by McDonald's criteria
  • Age 18 to 65 years, inclusive
  • A score minus one standard deviation below the mean on one or more of the following tests: PASAT, COWAT, CVLT-II, Stroop
  • EDSS 0 - 7.5, inclusive
  • No Ginkgo biloba in preceding 30 days
  • Native English speaker

Exclusion Criteria:

  • Current substance abuse disorder, psychosis, or significant depression (score on the Beck Depression Inventory II (BDI -II) greater than 28
  • Any significant uncontrolled medical problem including diabetes requiring insulin
  • Relapse of multiple sclerosis within the 30 days before screening
  • Abnormalities of coagulation or current use of anticoagulants or antiplatelet agents
  • Elective surgery planned for the study period or the following four weeks
  • Epilepsy or history of seizures
  • Use of nifedipine, nicardipine, Saint John's Wort, papaverine, mono amine oxidase inhibitors
  • Pregnancy or women not using a reliable form of contraception
  • Corrected binocular visual acuity worse than 20/50 or more than one error on binocular color vision testing with the Ishihara Color Plates or sustained nystagmus or diplopia on primary gaze
  • Inability to complete the neuropsychological test battery at the screening visit
  • History of alcohol abuse or illicit drug use in the prior six months
  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: NCT00841321

Locations
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
Sponsors and Collaborators
Investigators
Principal Investigator: Dennis N. Bourdette, MD Portland VA Medical Center, Portland, OR
  More Information

Additional Information:
Publications:
Responsible Party: Department of Veterans Affairs
ClinicalTrials.gov Identifier: NCT00841321     History of Changes
Other Study ID Numbers: B4368-R
Study First Received: February 9, 2009
Results First Received: October 22, 2013
Last Updated: May 23, 2014
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by Department of Veterans Affairs:
Ginkgo biloba
Multiple Sclerosis
Cognition
Neuropsychological Tests
Neurobehavioral Manifestations
Quality of life
Randomized Controlled Trials
Placebos
Double-Blind Method

Additional relevant MeSH terms:
Multiple Sclerosis
Sclerosis
Autoimmune Diseases
Autoimmune Diseases of the Nervous System
Demyelinating Autoimmune Diseases, CNS
Demyelinating Diseases
Immune System Diseases
Nervous System Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on November 27, 2014