Clinical trial NCT03145987: Effects of a Food Supplement on Cognitive and Neuropsychological Functioning in Older Adults.
Official title: A Randomized, Double-blinded, Clinical Trial on Effects of a Food Supplement on Cognitive and Neuropsychological Functioning in Healthy Older Adults.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cognitive Decline
Neurophysiologic Abnormality
Keywords: Cognitive functioning
Neuropsychological status
Vitis vinifera
Lead sponsor: Azienda Ospedaliera Universitaria Policlinico "G. Martino"
Sponsor class: OTHER
First posted: 2017-05-09
Enrollment: 111
Sex: ALL
Minimum age (years): 55
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, double-blinded, placebo controlled study.
Primary purpose: PREVENTION

Brief summary: The increase in life expectancy is associated with a gradual aging of the population so creating new needs arising from this new situation. Memory ability declines with age and memory deficits are regarded as an initial symptom of dementia of Alzheimer's Disease (AD) type, one of the most prevalent cognitive disorders in older people. States and scientific community have been called to find preventive strategies acting against the consequent physiological cognitive decline with the aim to attenuate the increase of dementia. Numerous studies have shown that polyphenolic compounds derived from multiple dietary sources, and more specifically the polyphenolic compounds found in grapes (GP), are able to attenuate the cognitive impairment and in reducing neuropathological lesions in the brain in experimental animal models for the study of Alzheimer's Disease (AD) .

In recent years, several in vivo studies have shown that oral administration of polyphenols from grapes improves antioxidant status in the brain and prevents neuronal damage induced by free radicals. The intake of proanthocyanidins, especially in the monomeric form, showed to produce an improvement of cognitive function in an Alzheimer's disorder animal model.

A randomized, double-blind, placebo-controlled clinical trial was designed by the investigators with the aim to evaluate potential beneficial effects of a Vitis vinifera-based food supplement on cognitive functioning and neuropsychological status in healthy older adults aging 55-75 years.

For the enrollment, mental status was evaluated through the Mini-Mental State Exam, a test able to provide quickly a screen of orientation, providing a rapid screen of recall, language, orientation, registration, attention and calculation. 111 subjects were recruited and, after obtaining the informed consent, successively randomly divided in two groups: Group 1, N = 57 to be treated for 12 weeks with Vitis vinifera extract (verum 250 mg/day); Group 2, N = 54 to be treated for 12 weeks with placebo. Cognitive functioning and neuropsychological status were evaluated at the beginning (before treatment) and a the end of treatment by using Mini Mental State Examination (MMSE), Beck Depression Inventory (BDI), Hamilton Anxiety Rating Scale (HARS) and Repeatable Battery for the Assessment of Neuropsychological Status.

Detailed description: Study design The study was a randomized into a two-group, parallel, placebo-controlled clinical trial to assess the efficacy of a food supplement containing vitis vinifera extract developed for cognitive and neuropsychological functioning in healthy older adults.

Screening Mental status was evaluated through the MMSE, a test able to provide quickly a screen of orientation, providing a rapid screen of recall, language, orientation, registration, attention and calculation. To study the effects on cognitive functioning and neuropsychological status participants were also subjected to the Beck Depression Inventory (BDI) and Hamilton Anxiety Rating Scale (HARS).

At screening (visit 1, day 0) after giving informed consent, subjects underwent medical history, physical examination, and vital signs. All subjects got oral and written information about the study and gave written informed consent to participate before inclusion in the trial. After screening and evaluation of baseline scores, included subjects were randomly allocated to one of two groups treated as follows: Group 1, N = 57 to be treated with Cognigrape capsule (verum 250 mg/day); Group 2, N = 54 to be treated with placebo . Randomisation by blocks of 3 (2 + 1) was double-blinded. Successive blocks were balanced by 2s. Neither subjects recruited for the study nor investigators were able to differentiate the two different treatments.

The Mini-Mental State Examination is composed of 12 items exploring through 22 trials verbal and performance, 7 cognitive functions: temporal and spatial orientation; immediate memory; attention and calculation; recall memory; language; praxia visuo-constructive. The administration requires a time ranging from 5 to 15 minutes. The score is corrected for age and education; the threshold for the purposes of enrollment in the study is set at a score ≥ 24. The MMSE score between 18 and 24 is an indication of a compromised moderate to mild, while a score of 25 is considered borderline, from 26 to 30 is indicative of normality cognitive. For this reason a score limit of 24 including masked potential light cognitive decline in healthy adults was chosen.

Beck Depression Inventory is a self-report instrument measuring the severity of depression. The Beck Depression Inventory (BDI) Short Form, a prominently and frequently cited, self-reported measure of depression was used. The 13-item questionnaire assesses 4 major components of depression: behavioral, affective, cognitive, and physiological. Numerical values assigned to each statement range from 0 to 3 indicating increasing severity. According to Beck's clinical criteria, a score between 8 and 15 indicates moderate depression and 16 severe depression.

Questionnaire is composed of in 21 questions with multiple choice response suitable to investigate the presence of depressive symptoms; aspects investigated by the test are: sadness, pessimism, sense of failure, dissatisfaction, guilty, free expectation, self-disappointment, self-accusation, suicidal ideas, crying, irritability, indecision, doubt, social withdrawal, devaluation of its image body, work efficiency decrease, sleep disturbance, fatigue, decreased appetite, weight loss, somatic concerns, loss of libido. The questionnaire has been administered immediately before the beginning (Day 0) and at the end of treatment (after 12 weeks).

Hamilton Anxiety Rating Scale is a scale evaluating anxiety through the investigation of 15 different areas (such as insomnia, mood, somatic symptoms). Each of the 15 areas is composed of a minimum of 3 to a maximum of 8 items to each of which is given a score from 0 to 6, depending on the severity of symptoms. Subsequently the total value is calculated for each area, using a score of 0 (absent), 1 (mild), 2 (moderate), 3 (severe), or 4 (very severe) points, based on the overall severity of symptoms investigating each specific area. The total score, which has been called "whole", is calculated by adding the points of each of the 15 areas surveyed. The rating of the scale may vary from 0 to 56. A total score around 18 is considered indicative of a pathological state.

Repeatable Battery for the Assessment of Neuropsychological Status is a quick and complete neuropsychological battery, consisting of two forms ( "A" and "B") associated with identical difficulty degrees, each divided into 12 subtests administered to evaluate 5 different cognitive domains: attention, language, visuospatial/constructional abilities immediate memory and delayed memory.

Cognitive-neuropsychological assessment was performed at baseline (o day) and after the 12 weeks of treatment period. Measures included MMSE, BDI, HARS, RBANS.

Eligibility criteria: Inclusion Criteria:

* age over 55 years; italian speaking and understanding; no using food supplements for cognitive functioning two weeks before enrolling and during the study period; score \> or = 24 at Mini-Mental State Exam (MMSE).

Exclusion Criteria:

* age \< 55 or \> 75 years, or AD or other related disorders, psychiatric or neurological diseases (including aphasia, sensory, motor or visual disturbances which could affect the test results), cancer, coagulation disorders, cardiovascular, lung, kidney, thyroid, liver, gastrointestinal disease or insulin-dependent diabetes, excessive consumption of alcohol or substance abuse/dependence; more than 3 medical hospitalizations last year or subjects taking coumadin, tricyclic antidepressants, antipsychotics, and anticonvulsants or any medications for cognitive functioning.

Primary outcomes:
measure: Mini Mental State Examination
timeFrame: Up to 12 weeks
measure: Beck Depression Inventory
timeFrame: Up to 12 weeks.
measure: Hamilton Anxiety Rating Scale
timeFrame: Up to 12 weeks.
measure: Repeatable Battery for the Assessment of Neuropsychological Status
timeFrame: Up to 12 weeks.
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Azienda Ospedaliera Universitaria "G Martino", Messina, Italy.
name: Umberto Alecci, MD
role: PRINCIPAL_INVESTIGATOR
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