Effect of a Polyphenol-rich Food Supplement on Cognitive Function in Healthy Aging Adults

Study Overview
=================
Brief Summary
-----------------
Several preliminary studies have shown that diet can have beneficial effects on cognitive decline. Among food shown to have such effects are some polyphenols from selected botanicals. Preclinical studies have concluded that polyphenols play a role in moderation of oxidative stress and inflammation, increased neuronal signaling, and improved metabolic function among other effects. Noteworthy, a positive and statistically significant association between the midlife level of polyphenol intake and cognitive function assessed 13 years later was found in a cohort of 2574 adults. Several mechanisms may be involved in these positive effects of food polyphenols on cognitive function in older adults: experimental studies suggest that polyphenols display neuroprotective effects, enhancement of the neuronal function, stimulation of brain flow and inducing neurogenesis, and might prevent age-related damage to the central nervous system through their antioxidant and anti-inflammatory activities. Based on these promising results, a food supplement from botanicals offering complementary polyphenol profile was developed. This food supplement is aimed to aid at maintenance of cognitive function in older adults.

Detailed Description
-----------------
This project aims to investigate the effects of 6 months supplementation with a polyphenol-rich supplement vs. placebo to consume daily on human cognitive function. Polyphenol-rich supplement and placebo will be provided as capsules matched for appearance. The study will be conducted as a randomized, double-blind, parallel-groups (2 arms) placebo-controlled, multicentre interventional design. Two groups, each of 102 volunteers, are studied. One group of volunteers will consume the polyphenol-rich product while the other one will consume the placebo product. Each volunteer will be seen for 3 visits at the investigational site, will have 2 follow-up calls and mid-term dietary survey. Baseline and follow-up visit will include cognitive assessment with the CANTAB battery. CANTAB tests will cover several aspects of memory: visio-spatial learning and episodic memory, verbal recognition memory and visio-spatial working memory. Moreover, psychological and mood components will be evaluated (mnesic complaint, depression, fatigue). Physical activity and food habits will also be recorded. Finally, biological parameters will be assessed (lipid profile, glycemia, insulinemia, CRPus, thyroid stimulating hormone, transthyretin, plasma level of phenolic compounds).

Official Title
-----------------
Effect of a Polyphenol-rich Food Supplement on Cognitive Function in Healthy Aging Adults: Randomized, Placebo-controlled, Double-blind Clinical Trial

Conditions
-----------------
Healthy Elderly

Intervention / Treatment
-----------------
* Dietary Supplement: Polyphenol-rich extract
* Dietary Supplement: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Independent subjects, living at home; Body Mass Index (BMI) 20-30 kg/m2 (limits included); 26 < MMSE score ≤ 29 Logical memory subtest of the Wechsler Memory Scale (16-69 years battery) sub-scores complying with the following: Immediate recall score < 29; Delayed recall score < 16; Exclusion Criteria: Evidence of actual major depressive disorder according to the module A of the Mini International Neuropsychiatric Interview (MINI); Subject consuming food supplements likely to have an effect on memory; High physical activity practice; Restrictive or unbalanced diet (hypocaloric, vegetarian, vegan, …) self-declared at V0; Diabetes; Cardiovascular disease diagnosed within less than 2 years, with the following exceptions: subjects with controlled (medicated) high blood pressure and/ or controlled (medicated) can be included; Personal history of Cerebrovascular Accident (CVA); Unbalanced thyroid disease; Anti-depressant treatment stopped since less than 3 months or still ongoing; Personal history of schizophrenia or other psychiatric disorders; Ongoing neuroleptic treatment; Uncorrected visual or auditory dysfunction (according to the volunteer's self-declaration); History of moderate to severe traumatic brain injury and / or intracranial surgery; Life threatening pathology (such as cancer) in remission for less than 1 year or still ongoing; General anesthesia in the last 6 months or planned in the next 6 months; Documented food allergy(ies), namely to one of the components of the study product; Psychological or linguistic incapability to sign the informed consent.

Ages Eligible for Study
-----------------
Minimum Age: 60 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>The placebo is a capsule with same appearance and organoleptic properties as the active product, containing no active component. Dose: 2 capsules per day, one capsule at least 1 hour after breakfast and one capsule at least one hour after dinner, with a glass of water. | Dietary Supplement: Placebo<br>* The placebo is a capsule with same appearance and organoleptic properties as the active product, containing no active component. Two groups, each of 102 volunteers, are studied. For 24 weeks, one group of volunteers will consume the active product (polyphenol-rich extract) while the other one will consume the placebo product.<br>|
| Experimental: Polyphenol-rich extract<br>The test product is a food supplement named Neurophenol. It is presented as a hard-shell capsule containing polyphenol-rich extracts. Dose: 2 capsules per day, one capsule at least 1 hour after breakfast and one capsule at least one hour after dinner, with a glass of water. | Dietary Supplement: Polyphenol-rich extract<br>* Two groups, each of 102 volunteers, are studied. For 24 weeks, one group of volunteers will consume the active product (polyphenol-rich extract) while the other one will consume the placebo product.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CANTAB - Paired Associate Learning test (PAL) |  | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CANTAB - Verbal Recognition Memory (VRM) |  | 24 weeks | 
| CANTAB - Spatial Span test (SSP) |  | 24 weeks | 
| CANTAB - Reverse Spatial Span test (Reverse SSP) |  | 24 weeks | 
| Wechsler Memory Scale - Logical memory subtest |  | 24 weeks | 
| McNair scale |  | 24 weeks | 
| Geriatric Depression Scale |  | 24 weeks | 
| Mini-Mental State Examination |  | 24 weeks | 
| Multidimensional Fatigue Inventory (MFI-20) |  | 24 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
polyphenols, memory, elderly