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

Cognitive Performance Clinical Trial

— AgilGinkgo  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04121728
• Other study ID #: 2018-02134 BASEC
• Status: Active, not recruiting
• Phase: N/A
• Start date: September 9, 2019
• Est. completion date: May 31, 2024

Study information

• Verified date: January 2023
• Source: University of Lausanne Hospitals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 16
• Est. completion date: May 31, 2024
• Est. primary completion date: May 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 55 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Age-related Cognitive Decline
• Cognitive Dysfunction
• Cognitive Performance
• Functional Capacity
• Subjective Cognitive Decline

Intervention

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.
• 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.

Locations

Country	Name	City	State
Switzerland	Centre Leenaards de la mémoire (CLM) CHUV	Lausanne	Vaud

Sponsors (2)

Lead Sponsor	Collaborator
Jean-François Démonet	University of Lausanne Hospitals

Country where clinical trial is conducted

Switzerland, 

References & Publications (6)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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