Subjective Cognitive Decline, Cognitive Performance, Functional Capacity, Age-related Cognitive Decline
Conditions
Keywords
metrological characteristics of EEG-ERP, Ginkgo Biloba
Brief summary
The objective of this study is to simultaneously establish the metrological characteristics of the new executive function markers (decision making and multiple flow management) derived from repeated ERP variations and to identify their ability to test whether a short treatment using Ginkgo biloba versus placebo extracts can modify the cognitive performance and functional capacity of patients in the very early stages of age-related cognitive decline. This trial, using subjects as their own control (cross-over) in repeated measurements will establish the reproducibility characteristics of the measurements and intra-individual variations of ERP over time in this population
Detailed description
This study is a single-center, randomized clinical trial testing the effects of Ginkgo biloba extracts versus placebo on event related potential ERP registration measurements in Electroencephalography (EEG) during neuropsychological tasks. The Hold-Release (HR) neuropsychological test allows the study of behavioral and neurofunctional correlates using several different techniques for online recording of brain activity. This test measures the engagement of focused attention and the loading of information into working memory, as opposed to the disengagement of attention. The study will be carried out in a randomized cross-over design, with Ginkgo vs. Placebo, or inversely, for 170 days each (approximately 6 months), separated by an 8-weeks wash-out period. A follow-up visit will be held 3 months after the last treatment of the study. The cross-over design uses each patient as its own control, which allows an easy comparison between the 2 groups Placebo vs. Ginkgo by limiting inter-patient variations. In addition, by doubling the number of patients per treatment compared to a classic study design in 2 groups, cross-over reduces the number of patients to be recruited, which facilitates recruitment on a single site. The study requires the recruitment of sixteen (16) informative participants with cognitive complaints.
Interventions
DRUGPlacebo
The placebo is presented in the form of capsules of identical mass, color and shape to those of the study product. It is composed of lactose, the excipients present in Symfona® 120 mg and colorants. The dosage is identical to that of the investigational product.
Symfona® commercial standardized Ginkgo biloba extracts are used in this study, at a rate of 2 capsules of 120 mg per day for 170 days.
Sponsors
University of Lausanne Hospitals
Jean-François Démonet
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
DIAGNOSTIC
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Investigational Medicinal Product (IMP), e.g Placebo and Ginkgo Biloba, is located and dispensed by Central Pharmacy. Only pharmacists are not blinded but they are neither involved in the conduct of the study not the analysis of the results
Intervention model description
randomized double-blind crossover design
Eligibility
Sex/Gender
ALL
Age
55 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
* Signed consent form * men and women * 60 to 80 years old * Diagnostic of Subjective complain * Understanding the 2 Hold-Release tasks in ERP
Exclusion criteria
* Montreal Cognitive Evaluation Score (MoCA) \<24 * Overall Clinical Dementia Rating (CDR) score \> 0.5 * Scores of the Hospital Anxiety and Depression Scale (HADS): HADS-A (Anxiety) \> 8 and/or HADS-D (Depression) \> 8 * Mild Cognitive Impairment (MCI) or dementia * Contraindication to MRI * Atrophy of any region of the brain as seen in the T1 volumetric MRI sequence * Any uncontrolled somatic or psychiatric condition * Bleeding disorders, and/or taking medications that increase the risk of bleeding, * Hypersensitivity to Ginkgo biloba or any of its excipients * Lactose intolerance * Treatment with barbiturates and/or neuroleptics * Ongoing treatment with Ginkgo biloba derivatives (a period of 2 months without treatment before inclusion is required
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in cognitive performance as assessed by variation in amplitude (mivroV) of the CNV component measured during the Hold-Release (HR) neuropsychological test after 6 months of Ginkgo biloba treatment | through study completion, an average of 14 months | the statistical model of repeated measurements of variance analysis will be used |
| Change in cognitive performance as assessed by variation in amplitude (mivroV) of the P300/P300' component measured during the Hold-Release (HR) neuropsychological test after 6 months of Ginkgo biloba treatment | through study completion, an average of 14 months | the statistical model of repeated measurements of variance analysis will be used |
| Reproducibility of contingent negative variation (CNV) event-related potential (ERP) component amplitude (microV) during the Hold-Release (HR) neuropsychological test | through study completion, an average of 14 months | Reproducibility of CNV will be assessed by interclass correlation coefficient (ICC) |
| Intra-individual variability of contingent negative variation (CNV) event-related potential (ERP) component amplitude (microV) during the Hold-Release (HR) neuropsychological test | through study completion, an average of 14 months | Intra-individual variability of CNV will be assessed by Interclass Coefficient Correlation (ICC) |
| Reproducibility of P300/P300' event-related potential (ERP) component amplitude (microV) during the Hold-Release (HR) neuropsychological test | through study completion, an average of 14 months | Reproducibility of P300/P300' will be assessed by Interclass Coefficient Correlation (ICC) |
| Intra-individual variability of P300/P300' event-related potential (ERP) component amplitude (microV) during the Hold-Release (HR) neuropsychological test | through study completion, an average of 14 months | Intra-individual variability of P300/P300' will be assessed by Interclass Coefficient Correlation (ICC) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Magnitude of repetition effects (Test-retest Reliability, TTR) on the contingent negative variation (CNV) event-related potential (ERP) component during the Hold-Release (HR) neuropsychological test. | through study completion, an average of 14 months | Combination of an analysis of variance (ANOVA) in repeated measurements and an analysis of variance (ANOVA) in correlation analysis will be used to assess respectively differences (microV) between measurement sessions and the existence of shared associations (correlation coefficient). |
| Magnitude of repetition effects (Test-retest Reliability, TTR) on P300/P300' event-related potential (ERP) component during the Hold-Release (HR) neuropsychological test. | through study completion, an average of 14 months | Combination of an analysis of variance (ANOVA) in repeated measurements and an analysis of variance (ANOVA) in correlation analysis will be used to assess respectively differences (microV) between measurement sessions and the existence of shared associations (correlation coefficient). |
| Association (correlation coefficient) between a transversal measurement of P300/P300' event-related potential (ERP) component during the Hold-Release (HR) neuropsychological test and the conventional verbal fluency scores. | through study completion, an average of 14 months | a mixed linear model approach will be applied to assess prediction |
| Association (correlation coefficient) between a transversal measurement of VPN event-related potential (ERP) component during the Hold-Release (HR) neuropsychological test and evolution of its own value during the participant's follow-up | through study completion, an average of 14 months | a mixed linear model approach will be applied to assess prediction |
| Association (correlation coefficient) between a transversal measurement of P300/P300' event-related potential (ERP) component during the Hold-Release (HR) neuropsychological test and evolution of its own value during the participant's follow-up | through study completion, an average of 14 months | a mixed linear model approach will be applied to assess prediction |
| Association (correlation coefficient) between a transversal measurement of VPN event-related potential (ERP) component during the Hold-Release (HR) neuropsychological test and the conventional verbal fluency scores. | through study completion, an average of 14 months | a mixed linear model approach will be applied to assess prediction |
| Change in cognitive performance as assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) test after 6 months of Ginkgo biloba treatment | 6 months | the statistical model of repeated measurements of variance analysis will be used |
| Change in scores of categorical semantic verbal fluency after 6 months of Ginkgo biloba treatment | 6 months | the statistical model of repeated measurements of variance analysis will be used |
| Change in scores of verbal fluency letter instruction after 6 months of Ginkgo biloba treatment | 6 months | the statistical model of repeated measurements of variance analysis will be used |
| Change in anxiety and depression as assessed using the Hospital Anxiety and Depression Scale (HAD-A/D) after 6 months of Ginkgo biloba treatment | 6 months | the statistical model of repeated measurements of variance analysis will be used |
| Change in reaction time (ms) during the Hold-Release (HR) neuropsychological test after 6 months of Ginkgo biloba treatment | 6 months | the statistical model of repeated measurements of variance analysis will be used |
Other
| Measure | Time frame | Description |
|---|---|---|
| Predictive metrological characteristics of ERP modulation in term of its ability to detect a more sensitive cognitive variation than usual method | through study completion, an average of 14 months | a mixed linear model approach will be applied to assess prediction |
| Predictive metrological characteristics of ERP modulation in term of its ability to detect a slope break during cognitive decline | through study completion, an average of 14 months | a mixed linear model approach will be applied to assess prediction |
Countries
Switzerland
Outcome results
None listed