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

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

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

Study Overview

• Status: Active, not recruiting
• Conditions: Cognitive Performance; Functional Capacity; Subjective Cognitive Decline; Age-related Cognitive Decline
• Intervention / Treatment: Drug: Ginkgo biloba extract; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Vaud
    • Lausanne, Vaud, Switzerland, 1011
      • Centre Leenaards de la mémoire (CLM) CHUV

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Group Ginkgo-Placebo; 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; 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.; Other Names: Symfona®; Drug: Placebo; 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.; Other Names: Placebo caps
Other: Group Placebo-Ginkgo; 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; 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.; Other Names: Symfona®; Drug: Placebo; 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.; Other Names: Placebo caps

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Predictive metrological characteristics of ERP modulation in term of its ability to detect a more sensitive cognitive variation than usual method	a mixed linear model approach will be applied to assess prediction	through study completion, an average of 14 months
Predictive metrological characteristics of ERP modulation in term of its ability to detect a slope break during cognitive decline	a mixed linear model approach will be applied to assess prediction	through study completion, an average of 14 months

Collaborators and Investigators

• Sponsor: Jean-François Démonet
• Collaborators: University of Lausanne Hospitals
• Investigators: Principal Investigator: Jean-François Démonet, Prof, Universitary Lausanne Hospital

Publications and helpful links

General Publications

• Amieva H, Le Goff M, Millet X, Orgogozo JM, Peres K, Barberger-Gateau P, Jacqmin-Gadda H, Dartigues JF. Prodromal Alzheimer's disease: successive emergence of the clinical symptoms. Ann Neurol. 2008 Nov;64(5):492-8. doi: 10.1002/ana.21509.
• Luck T, Luppa M, Matschinger H, Jessen F, Angermeyer MC, Riedel-Heller SG. Incident subjective memory complaints and the risk of subsequent dementia. Acta Psychiatr Scand. 2015 Apr;131(4):290-6. doi: 10.1111/acps.12328. Epub 2014 Sep 9.
• Thierry G, Doyon B, Demonet JF. ERP mapping in phonological and lexical semantic monitoring tasks: A study complementing previous PET results. Neuroimage. 1998 Nov;8(4):391-408. doi: 10.1006/nimg.1998.0371.
• Martin CD, Thierry G, Demonet JF. ERP characterization of sustained attention effects in visual lexical categorization. PLoS One. 2010 Mar 25;5(3):e9892. doi: 10.1371/journal.pone.0009892.
• Tan MS, Yu JT, Tan CC, Wang HF, Meng XF, Wang C, Jiang T, Zhu XC, Tan L. Efficacy and adverse effects of ginkgo biloba for cognitive impairment and dementia: a systematic review and meta-analysis. J Alzheimers Dis. 2015;43(2):589-603. doi: 10.3233/JAD-140837.
• Kennedy DO, Scholey AB, Drewery L, Marsh VR, Moore B, Ashton H. Electroencephalograph effects of single doses of Ginkgo biloba and Panax ginseng in healthy young volunteers. Pharmacol Biochem Behav. 2003 Jun;75(3):701-9. doi: 10.1016/s0091-3057(03)00120-5.

Study record dates

Study Major Dates

• Study Start (Actual): September 9, 2019
• Primary Completion (Anticipated): May 31, 2024
• Study Completion (Anticipated): May 31, 2024

Study Registration Dates

• First Submitted: September 18, 2019
• First Submitted That Met QC Criteria: October 7, 2019
• First Posted (Actual): October 10, 2019

Study Record Updates

• Last Update Posted (Estimate): January 11, 2023
• Last Update Submitted That Met QC Criteria: January 9, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Ginkgo Biloba; metrological characteristics of EEG-ERP
• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction
• Other Study ID Numbers: 2018-02134 BASEC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No