Trial of a Nutritional Blend to Prevent Cognitive Decline in Older Adults

To demonstrate the beneficial effects of 1-year intervention with a nutritional blend of ingredients on blood levels of nutritional biomarkers known to be linked with cognitive decline in non-demented adults with subjective memory concerns aged 70+ years

Study Overview

• Status: Completed
• Conditions: Cognitive Decline
• Intervention / Treatment: Dietary supplement: Control; Dietary supplement: Nutrional blend of ingredients including vitamins and fish oil

Detailed Description

This multicenter trial will be a placebo-controlled, double-blind, randomized, 2 parallel groups study. The subjects will be randomly allocated to one of two treatment groups (placebo or nutrition product). The duration of the intervention is 1 year.

The total sample size at baseline is 364 subjects, consisting of non-demented adults with subjective memory concerns aged 70+ years.

• Study Type: Interventional
• Enrollment (Actual): 362
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Toulouse, France, 31059
    • CHU Toulouse

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 70 years and older (OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥ 70 years
2. Spontaneous memory complaints
3. Adequate fluency in the local language to understand the inform consent form and complete any other study document
4. Sufficient vision and hearing to complete study protocol procedures based on medical judgement
5. Has a study partner that is willing to participate as a source of information and has at least weekly contact with the participant (contact can be in-person, via telephone or electronic communication)
6. Has general health status that will not interfere with the ability to complete the study
7. Willing and able to participate and to give written consent to comply with study procedures
8. Willing to be informed in case a new clinical pathology is discovered through clinical examinations

Exclusion Criteria:

1. Exhibiting a loss of independence in basic activities of daily living (ADL score < 4)
2. MMSE score < 24
3. Dementia as determined by DSM-V criteria
4. Suffering from diseases that are likely to be life-threatening in the short-term
5. History or presence of a severe disease (e.g., cardiovascular, hepatic, renal (e.g., End Stage Renal Disease), gastroenteral, respiratory, endocrine, neurologic, psychiatric, immunologic, or hematologic disease or other conditions) that could, in the opinion of the investigator, interfere with the subjects safety or ability to complete the trial
6. Food allergy
7. Taking omega-3 dietary supplements containing >200 mg DHA per day during the last 6 months
8. Receiving or having received in the past 3 months a physician prescribed vitamin B12, B3 or vitamin B-complex
9. Receiving Alzheimer's Disease medication (Galantamine, Memantine Donezepil and Rivastigmine)
10. Deprived of their liberty by administrative or judicial decision, or under guardianship or admitted to a healthcare or social institution (subjects in non-assisted living facilities could be recruited).

11. Having participated in another clinical study in the previous month or is currently participating in another study.

    Subjects meeting one or more of the following criteria below will not be included in the PET scan and MRI-scan subset groups:

12. Wearing a pace-maker or having metal in the body which is exclusionary for MRI
13. Claustrophobic

Subjects who will participate in the PET-scan and MRI-scan subset groups, will be excluded for a 1-year period of any future projects involving investigations using ionizing radiation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SUPPORTIVE_CARE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Experimental; Nutritional blend of ingrédients including vitamins and fish oil	Dietary supplement: Nutrional blend of ingredients including vitamins and fish oil
PLACEBO_COMPARATOR: Control comparator: control product does not contain any of the active ingredients and is matched for carbohydrate content to the active intervention.	Dietary supplement: Control

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes at 1 year in levels of nutritional risk factors involved in cognitive decline with ageing relative to baseline	Plasma erythrocyte-omega 3 index	[Time Frame: 1 year] [Safety Issue: No]
Changes at 1 year in levels of nutritional risk factors involved in cognitive in cognitive decline with ageing relative to baseline	Homocysteine levels	[Time Frame: 1 year] [Safety Issue: No]

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in cognitive function determined by a composite Z-score from 4 neuropsychological tests (see description) at 0, 6 and 12 months	The composite score combines the scores of the following neuropsychological tests: FCSRT score as the sum of free recall (sum of the three learning tests) and of cued recall (sum of free recall and indexed recall), Orientation score (10 items) from MMSE, Number of symbols reported during 90 sec (Digit symbol Substitution test) and the Number of words reported during 2-minutes (Category naming test)	[Time Frame: 1 year] [Safety Issue: No]
Changes in cognitive function assessed by the FCSRT (Free and Cued Selective Reminding Test) at 0, 6 and 12 months	FCSRT score as the sum of free recall (sum of the three learning tests) and of cued recall (sum of free recall and indexed recall)	[Time Frame: 1 year] [Safety Issue: No]
Changes in cognitive function assessed by the Orientation score from the Mini Mental Scale Examination (MMSE) at 0, 6 and 12 months	Orientation score: Subcale of MMSE (see outcome 8); score from 0 to 10.	[Time Frame: 1 year] [Safety Issue: No]
Changes in cognitive function assessed by the WAIS-IV coding test at 0, 6 and 12 months	Number of symbols reported during 90 seconds	[Time Frame: 1 year] [Safety Issue: No]
Changes in cognitive function assessed by the Category Naming Test (CNT) at 0, 6 and 12 months	Number of words reported during 2 minutes	[Time Frame: 1 year] [Safety Issue: No]
Cognitive function assessed by the (Mini Mental Scale Examination) MMSE total score at 6 and 12 months	Total score of the MMSE from 0 to 30. Any score greater than or equal to 24 points (out of 30) indicates a normal cognition. Below this, scores can indicate severe (≤9 points), moderate (10-18 points) or mild (19-23 points) cognitive impairment.	[Time Frame: 1 year] [Safety Issue: No]
Cognitive status changes assessed by the Trail Making Test parts A and B at 0, 6 and 12 months	Time in sec to complete Trail Making Test parts A and B	[Time Frame: 1 year] [Safety Issue: No]
Cognitive status changes assessed by the Logical Memory subtest of the WMS-R Test at 0, 6 and 12 months	Number of correct story elements recalled	[Time Frame: 1 year] [Safety Issue: No]
Cognitive status changes assessed by the Letter Fluency Test at 0, 6 and 12 months	Number of correct words reported in 2 minutes	[Time Frame: 1 year] [Safety Issue: No]
Cognitive status changes assessed by the Stroop Color Word Test (SCWT) at 0, 6 and 12 months	Time required to complete each sub-test and interference measure	[Time Frame: 1 year] [Safety Issue: No]
Cognitive status changes assessed by the Digit Span (DS) at 0, 6 and 12 months	Number of digits recalled for forwards and backward sequences	[Time Frame: 1 year] [Safety Issue: No]
Change in cognitive impairment assessed by the Clinical Dementia Rating - Sum of Boxes (CDR-SOB) at 0 and 12 months	CDR-SOB score ranging from 0 to 18 (0: Normal ; 0.5-4: Questionable cognitive impairment ; 4.5-9: Mild dementia ; 9.5-15.5: Moderate dementia ; 16-18: Severe dementia)	[Time Frame: 1 year] [Safety Issue: No]
Change in clinical status assessed by Clinical Dementia Rating (CDR) at 0 and 12 months	Conversion rates to Mild cognitive impairment (MCI) and to dementia (0 = Normal, 0.5= very mild dementia, 1= mild dementia, 2 = moderate dementia, 3= severe dementia)	[Time Frame: 1 year] [Safety Issue: No]
Subjective change in cognitive function assessed by the PROMIS Applied Cognition - Abilities instrument, Cognitive Function Instrument at 0, 1 and 12 months	PROMIS score: 33 items noted from 0 to 5 (Min score= 0, Max score =165) not used as diagnosis score but to assess the performance from baseline	[Time Frame: 1 year] [Safety Issue: No]
Subjective change in quality of life and health status assessed by the EQ-5D-5L questionnaire at 0 and 12 months	EQ-5D-5L score: EQ-5D-5L, 5 item questionnaire and a visual analogue scale ranging from 0-100 to describe health status	[Time Frame: 1 year] [Safety Issue: No]
Changes in depression status assessed by the Geriatric depression scale (GDS) at 0 and 12 months	GDS score ranging from 0 to 15: 0-9: Normal ; 10-19: Mild depression ; 20-30 : Severe depression.	[Time Frame: 1 year] [Safety Issue: No]
Changes in depression, anxiety and psychiatric symptoms assessed by the Neuropsychiatric Inventory Questionnaire (NPI-Q) at 0 and 12 months	Change in the presence (yes-no) and severity score (1: mild; 2: moderate; 3: severe) of 12 neuropsychiatric symptoms related to dementia, as well as informant distress score for each of the present symptoms (from 0: 'No distress' to 5: 'Extreme distress') measured at 0 and 12 months.	[Time Frame: 1 year] [Safety Issue: No]
Changes in physical functions assessed by the Short Physical Performance Battery (SPPB) at 0, 6 and 12 months	SPPB score ranging from 0 to 12. Assessment of score's evolution from baseline to 12 months.	[Time Frame: 1 year] [Safety Issue: No]
Changes in frailty syndromes assessed by the Fried Frailty Criteria at 0 and 12 months	Grip strength, timed walking, involuntary weight loss, fatigue and physical activity (categories: robust, pre-frail, frail)	[Time Frame: 1 year] [Safety Issue: No]
Changes in brain structure assessed by Magnetic Resonance Imaging (MRI) in a subset of the study population at 0 and 12 months	Regional tissue volume, Regional tissue thickness, Regional surface area, Intracranial volume (total, regional), Total brain volume, Regional volume (eg hippocampus)	[Time Frame: 1 year] [Safety Issue: No]
Changes in brain structure assessed by fluid-attenuated inversion recovery (FLAIR) MRI and diffusion tensor imaging (DTI) in a subset of the study population at 0 and 12 months	Total white matter lesion volume	[Time Frame: 1 year] [Safety Issue: No]
Changes in brain function assessed by Arterial spin label (ASL) perfusion MRI in a subset of the study population at 0 and 12 months	Cerebral blood flow	[Time Frame: 1 year] [Safety Issue: No]
Changes in brain function assessed by resting State fMRI in a subset of the study population at 0 and 12 months	Brain connectivity	[Time Frame: 1 year] [Safety Issue: No]
Changes in brain structure assessed by MRI diffusion tensor imaging (DTI) in a subset of the study population at 0 and 12 months	White matter integrity	[Time Frame: 1 year] [Safety Issue: No]
Changes in brain function assessed by Amyloid Florbetapir Positron Emission Tomography (PET) in a subset of the study population at baseline	Amyloid load	[Time Frame: 1 years] [Safety Issue: No]
Changes in levels of biomarkers associated with cognitive decline: BDNF levels at 0, 6 and 12 months	Brain-Derived Neurotrophic Factor (BDNF) plasma levels	[Time Frame: 1 year] [Safety Issue: No]
Changes in levels of biomarkers associated with cognitive decline: Aβ40 levels at 0, 6 and 12 months	Aβ40 plasma levels	[Time Frame: 1 year] [Safety Issue: No]
Changes in levels of biomarkers associated with cognitive decline: Aβ42 levels at 0, 6 and 12 months	Aβ42 plasma levels	[Time Frame: 1 year] [Safety Issue: No]
Changes in levels of biomarkers associated with cognitive decline: Tau protein levels at 0, 6 and 12 months	Tau protein plasma levels	[Time Frame: 1 year] [Safety Issue: No]
Changes in levels of biomarkers associated with cognitive decline: Asymmetric dimethylarginine levels at 0, 6 and 12 months	Asymmetric dimethylarginine plasma levels	[Time Frame: 1 year] [Safety Issue: No]
Changes in levels of biomarkers associated with cognitive decline: Homocysteine levels at 0, 6 and 12 months	Homocysteine plasma levels	[Time Frame: 1 year] [Safety Issue: No]
Changes in levels of blood plasma inflammatory markers 0, 6 and 12 months	Inflammatory markers (sCAMs, E-Selectin, TNF-alpha, IL1, IL6, IL10, CRP, neopterin)	[Time Frame: 1 year] [Safety Issue: No]
Changes in levels of blood plasma markers of oxidative stress at 0, 6 and 12 months	Markers of oxidative stress (Oxidized Low-density lipoprotein (oxLDL), F2-isoprostane)	[Time Frame: 1 year] [Safety Issue: No]
Changes in levels of plasma nutrient levels at 0, 6 and 12 months	e.g.vitamins, minerals, lipids, amino acids, erythrocyte omega-3 index	[Time Frame: 1 year] [Safety Issue: No]
Treatment effects in a subgroup population defined by the below described subject characteristic:	Clinical Dementia Rating (CDR) of 0.5 at baseline	[Time Frame: 1 year] [Safety Issue: No]
Treatment effects in a subgroup population defined by the below described subject characteristic:	Low DHA status (erythrocyte omega 3 index in the lower quartile) at baseline	[Time Frame: 1 year] [Safety Issue: No]
Treatment effects in a subgroup population defined by the below described subject characteristic:	High plasma homocysteine levels (plasma homocysteine ≥ 12 µmol/L) at baseline	[Time Frame: 1 year] [Safety Issue: No]
Treatment effects in a subgroup population defined by the below described subject characteristic:	CAIDE (Cardiovascular Risk Factors, Aging and Dementia) risk score at baseline	[Time Frame: 1 year] [Safety Issue: No]
Treatment effects in a subgroup population defined by the below described subject characteristic:	Genotype	[Time Frame: 1 year] [Safety Issue: No]

Collaborators and Investigators

• Sponsor: Nestlé
• Collaborators: University Hospital, Toulouse
• Investigators: Principal Investigator: Bruno VELLAS, CHU Toulouse, Gérontopôle, Cité de la Santé, 20 Rue du Pont Saint Pierre, 31059 TOULOUSE Cedex 9

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 1, 2016
• Primary Completion (ACTUAL): February 26, 2019
• Study Completion (ACTUAL): February 26, 2019

Study Registration Dates

• First Submitted: October 18, 2016
• First Submitted That Met QC Criteria: March 9, 2017
• First Posted (ACTUAL): March 15, 2017

Study Record Updates

• Last Update Posted (ACTUAL): May 23, 2019
• Last Update Submitted That Met QC Criteria: May 22, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: Aging population
• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction; Physiological Effects of Drugs; Micronutrients; Vitamins
• Other Study ID Numbers: 16.13.NRC; 2016-A01006-45, RC31/16/8196 (REGISTRY: ANSM)

Plan for Individual participant data (IPD)

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