Clinical trial NCT02063646: Effect of a Polyphenol-rich Food Supplement on Cognitive Function in Healthy Aging Adults
Official title: Effect of a Polyphenol-rich Food Supplement on Cognitive Function in Healthy Aging Adults: Randomized, Placebo-controlled, Double-blind Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy Elderly
Keywords: polyphenols
memory
elderly
Lead sponsor: Neurophenols Consortium
Sponsor class: OTHER
Collaborators: name: Activ'inside
name: Atrium Innovations
name: Fruit d'Or
name: Laboratoire NutriNeuro Université de Bordeaux/INRA
name: NutraCanada
name: Laval University
First posted: 2014-02-14
Enrollment: 204
Sex: ALL
Minimum age (years): 60
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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).

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.

Primary outcomes:
measure: CANTAB - Paired Associate Learning test (PAL)
timeFrame: 24 weeks
Secondary outcomes:
measure: CANTAB - Verbal Recognition Memory (VRM)
timeFrame: 24 weeks
measure: CANTAB - Spatial Span test (SSP)
timeFrame: 24 weeks
measure: CANTAB - Reverse Spatial Span test (Reverse SSP)
timeFrame: 24 weeks
measure: Wechsler Memory Scale - Logical memory subtest
timeFrame: 24 weeks
measure: McNair scale
timeFrame: 24 weeks
measure: Geriatric Depression Scale
timeFrame: 24 weeks
measure: Mini-Mental State Examination
timeFrame: 24 weeks
measure: Multidimensional Fatigue Inventory (MFI-20)
timeFrame: 24 weeks
Other outcomes:
measure: Lipid profile
timeFrame: 24 weeks
measure: Insulinemia and glycemia
timeFrame: 24 weeks
measure: Inflammatory markers
timeFrame: 24 weeks
measure: Hormones
timeFrame: 24 weeks
measure: Urinary polyphenols
timeFrame: 24 weeks
measure: Fatty acid profile in erythrocyte membranes
timeFrame: 24 weeks
measure: Retinol Binding Protein and Transtyretin
timeFrame: 24 weeks
measure: Nuclear receptor expression in mononuclear cells
timeFrame: 24 weeks
measure: Gene expression in mononuclear cells by microarray approach
timeFrame: 24 weeks
measure: Epigenetic markers
timeFrame: 24 weeks
Locations:
city: Québec
country: Canada
facility: INAF (Institute of nutrition and functionnal foods)
state: Quebec
city: Saint-Herblain
country: France
facility: Biofortis
Study officials:
affiliation: Laval University
name: Carol Hudon, Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Laboratoire NutriNeuro Université de Bordeaux/INRA
name: Véronique Pallet, Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Laval University
name: Catherine Bégin, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Krikorian R, Boespflug EL, Fleck DE, Stein AL, Wightman JD, Shidler MD, Sadat-Hossieny S. Concord grape juice supplementation and neurocognitive function in human aging. J Agric Food Chem. 2012 Jun 13;60(23):5736-42. doi: 10.1021/jf300277g. Epub 2012 Apr 9.
citation: Kesse-Guyot E, Fezeu L, Andreeva VA, Touvier M, Scalbert A, Hercberg S, Galan P. Total and specific polyphenol intakes in midlife are associated with cognitive function measured 13 years later. J Nutr. 2012 Jan;142(1):76-83. doi: 10.3945/jn.111.144428. Epub 2011 Nov 16.
citation: Rossi L, Mazzitelli S, Arciello M, Capo CR, Rotilio G. Benefits from dietary polyphenols for brain aging and Alzheimer's disease. Neurochem Res. 2008 Dec;33(12):2390-400. doi: 10.1007/s11064-008-9696-7. Epub 2008 Apr 16.
citation: Spencer JP, Vauzour D, Rendeiro C. Flavonoids and cognition: the molecular mechanisms underlying their behavioural effects. Arch Biochem Biophys. 2009 Dec;492(1-2):1-9. doi: 10.1016/j.abb.2009.10.003. Epub 2009 Oct 12.
citation: Vauzour D, Vafeiadou K, Rodriguez-Mateos A, Rendeiro C, Spencer JP. The neuroprotective potential of flavonoids: a multiplicity of effects. Genes Nutr. 2008 Dec;3(3-4):115-26. doi: 10.1007/s12263-008-0091-4.