Modulation of Attention in Event Related Potential (ERPs) as a Marker of Early Cognitive Decline by Ginkgo Biloba

Study Overview
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Brief Summary
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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
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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.

Official Title
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Evaluation of the Modulation of Attention Explored in ERPs as a Marker of Early Cognitive Decline: Concept Validation on the Effect of Ginkgo Biloba Extracts. Randomized, Double-blind, Cross-over, Placebo-controlled Study

Conditions
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Subjective Cognitive Decline, Cognitive Performance, Functional Capacity, Age-related Cognitive Decline

Intervention / Treatment
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* Drug: Ginkgo biloba extract
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: randomized double-blind crossover design
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Group Ginkgo-Placebo<br>Cross-over design: In Group Ginkgo-Placebo participants are allocated first to the IMP Symfona® during 6 months and after 2 months of wash-out period are allocated to the placebo for 6 months. | Drug: Ginkgo biloba extract<br>* 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.<br>* Other names: Symfona®;Drug: Placebo<br>* 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.<br>* Other names: Placebo caps;|
| Other: Group Placebo-Ginkgo<br>Cross-over design:In Group Placebo-Ginkgo participants are allocated first to the placebo during 6 months and after 2 months of wash-out period are allocated the IMP Symfona® for 6 months. | Drug: Ginkgo biloba extract<br>* 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.<br>* Other names: Symfona®;Drug: Placebo<br>* 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.<br>* Other names: Placebo caps;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reproducibility of contingent negative variation (CNV) event-related potential (ERP) component amplitude (microV) during the Hold-Release (HR) neuropsychological test | Reproducibility of CNV will be assessed by interclass correlation coefficient (ICC) | through study completion, an average of 14 months | 
| Intra-individual variability of contingent negative variation (CNV) event-related potential (ERP) component amplitude (microV) during the Hold-Release (HR) neuropsychological test | Intra-individual variability of CNV will be assessed by Interclass Coefficient Correlation (ICC) | through study completion, an average of 14 months | 
| Reproducibility of P300/P300' event-related potential (ERP) component amplitude (microV) during the Hold-Release (HR) neuropsychological test | Reproducibility of P300/P300' will be assessed by Interclass Coefficient Correlation (ICC) | through study completion, an average of 14 months | 
| Intra-individual variability of P300/P300' event-related potential (ERP) component amplitude (microV) during the Hold-Release (HR) neuropsychological test | Intra-individual variability of P300/P300' will be assessed by Interclass Coefficient Correlation (ICC) | through study completion, an average of 14 months | 
| 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 | the statistical model of repeated measurements of variance analysis will be used | through study completion, an average of 14 months | 
| 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 | the statistical model of repeated measurements of variance analysis will be used | through study completion, an average of 14 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | the statistical model of repeated measurements of variance analysis will be used | 6 months | 
| Change in scores of categorical semantic verbal fluency after 6 months of Ginkgo biloba treatment | the statistical model of repeated measurements of variance analysis will be used | 6 months | 
| Change in scores of verbal fluency letter instruction after 6 months of Ginkgo biloba treatment | the statistical model of repeated measurements of variance analysis will be used | 6 months | 
| Change in anxiety and depression as assessed using the Hospital Anxiety and Depression Scale (HAD-A/D) after 6 months of Ginkgo biloba treatment | the statistical model of repeated measurements of variance analysis will be used | 6 months | 
| Change in reaction time (ms) during the Hold-Release (HR) neuropsychological test after 6 months of Ginkgo biloba treatment | the statistical model of repeated measurements of variance analysis will be used | 6 months | 
| 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. | 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). | through study completion, an average of 14 months | 
| Magnitude of repetition effects (Test-retest Reliability, TTR) on P300/P300' event-related potential (ERP) component during the Hold-Release (HR) neuropsychological test. | 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). | through study completion, an average of 14 months | 
| 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. | a mixed linear model approach will be applied to assess prediction | through study completion, an average of 14 months | 
| 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. | a mixed linear model approach will be applied to assess prediction | through study completion, an average of 14 months | 
| 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 | a mixed linear model approach will be applied to assess prediction | through study completion, an average of 14 months | 
| 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 | a mixed linear model approach will be applied to assess prediction | through study completion, an average of 14 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metrological characteristics of EEG-ERP, Ginkgo Biloba