Multiple SclerosisPhase 2NCT00841321
Trial of Ginkgo as a Treatment for Cognitive Problems in Multiple Sclerosis
A Phase 2 study testing Ginkgo biloba in people with Multiple Sclerosis and Cognitive Ability, General, run by US Department of Veterans Affairs at 2 sites in United States.
Trial summary
The purpose of this study is to see if treatment with Ginkgo improves cognitive function in people with multiple sclerosis who have cognitive problems. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Multiple Sclerosis, Cognitive Ability, General
- What is being tested?
- Ginkgo biloba
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 2 sitesUnited States
- Study dates
- Jan 2009to Dec 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Portland VA Medical Center, Portland, OR
Portland, Oregon, 97239
VA Puget Sound Health Care System, Seattle
Seattle, Washington, 98108
About this study
Official title: Ginkgo Biloba for Cognitive Impairment in Multiple Sclerosis
The purpose of this study is to see if treatment with Ginkgo improves cognitive function in people with multiple sclerosis who have cognitive problems.
Read the 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.
- Conditions
- Multiple Sclerosis, Cognitive Ability, General
- Being tested
- Ginkgo biloba, Placebo
- Keywords
- Ginkgo biloba, Multiple Sclerosis, Cognition, Neuropsychological Tests, Neurobehavioral Manifestations, Quality of life, Randomized Controlled Trials, Placebos, Double-Blind Method
- Medical subject headings
- Multiple Sclerosis, Neurobehavioral Manifestations
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ginkgo bilobaDrug
Also called EGb 761
120 mg orally twice a day for 12 weeks
PlaceboDrug
One capsule orally twice a day for 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Active comparator | Subjects with multiple sclerosis and documented cognitive impairment will be randomized to take the intervention or placebo. Receives: Drug: Ginkgo biloba |
| Arm 2 | Placebo comparator | Subjects with multiple sclerosis and documented cognitive impairment will be randomized to receive the placebo. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
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.
Measured: 12 weeks
Secondary outcomes (1)
Secondary Outcome: Measures of Self-report as Well as Family Reports of Subject's Cognitive Deficits and Assessment of Social Integration.
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.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2009 (estimated)
- Study startJan 2009
- Primary completionNov 2010
- Study completionDec 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- US Department of Veterans Affairs
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Dennis N. Bourdette, MD, Principal investigator, Portland VA Medical Center, Portland, OR
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00841321
- Sponsor's protocol ID
- B4368-R
- Status last verified
- May 2014
- First submitted
- 9 Feb 2009
- Last updated
- 6 Jun 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Lovera JF, Kim E, Heriza E, Fitzpatrick M, Hunziker J, Turner AP, Adams J, Stover T, Sangeorzan A, Sloan A, Howieson D, Wild K, Haselkorn J, Bourdette D. Ginkgo biloba does not improve cognitive function in MS: a randomized placebo-controlled trial. Neurology. 2012 Sep 18;79(12):1278-84. doi: 10.1212/WNL.0b013e31826aac60. Epub 2012 Sep 5.
PubMed 22955125Hughes AJ, Parmenter BA, Haselkorn JK, Lovera JF, Bourdette D, Boudreau E, Cameron MH, Turner AP. Sleep and its associations with perceived and objective cognitive impairment in individuals with multiple sclerosis. J Sleep Res. 2017 Aug;26(4):428-435. doi: 10.1111/jsr.12490. Epub 2017 Jan 17.
PubMed 28093823
Study at a glance
From the registry record, last updated by the sponsor on 6 Jun 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ginkgo Biloba for Cognitive Impairment in Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT00841321
- Acronym / sponsor ID
- B4368-R
- Conditions
- Multiple Sclerosis, Cognitive Ability, General
- Keywords
- Ginkgo biloba, Multiple Sclerosis, Cognition, Neuropsychological Tests, Neurobehavioral Manifestations, Quality of life, Randomized Controlled Trials, Placebos
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 120 participants (actual)
- Lead sponsor
- US Department of Veterans AffairsUS federal agency
- Study start
- Jan 2009
- Primary completion
- Nov 2010 (actual)
- Study completion
- Dec 2010 (actual)
- First posted
- 11 Feb 2009 (estimated)
- Results
- Posted 5 May 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to see if treatment with Ginkgo improves cognitive function in people with multiple sclerosis who have cognitive problems.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Active comparator | Drug: Ginkgo bilobaSubjects with multiple sclerosis and documented cognitive impairment will be randomized to take the intervention or placebo. |
| Arm 2 | Placebo comparator | Drug: PlaceboSubjects with multiple sclerosis and documented cognitive impairment will be randomized to receive the placebo. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ginkgo bilobaAlso: EGb 761120 mg orally twice a day for 12 weeks | Drug | Arm 1 |
| PlaceboOne capsule orally twice a day for 12 weeks | Drug | Arm 2 |
Primary outcome
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.
1 secondary outcome
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jun 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 22955125Lovera JF, Kim E, Heriza E, Fitzpatrick M, Hunziker J, Turner AP, Adams J, Stover T, Sangeorzan A, Sloan A, Howieson D, Wild K, Haselkorn J, Bourdette D. Ginkgo biloba does not improve cognitive function in MS: a randomized placebo-controlled trial. Neurology. 2012 Sep 18;79(12):1278-84. doi: 10.1212/WNL.0b013e31826aac60. Epub 2012 Sep 5.
- Derived from this study: PubMed 28093823Hughes AJ, Parmenter BA, Haselkorn JK, Lovera JF, Bourdette D, Boudreau E, Cameron MH, Turner AP. Sleep and its associations with perceived and objective cognitive impairment in individuals with multiple sclerosis. J Sleep Res. 2017 Aug;26(4):428-435. doi: 10.1111/jsr.12490. Epub 2017 Jan 17.
- Department of Veteran Affairs MS Centers of ExcellenceLink provided by the sponsor.
- MS Center of OregonLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dennis N. Bourdette, MD principal investigator
Portland VA Medical Center, Portland, OR
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ginkgo biloba in people with Multiple Sclerosis and Cognitive Ability, General, run by US Department of Veterans Affairs at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Jun 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 May 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00841321, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jun 2014.