Effect of Vitamin D on Cognitive Decline of Patients With Memory Complaint

Study Overview
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Brief Summary
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As recommended allowance of oral vitamine D are unable to ensure the recommended serum concentration of vitamine D, the purpose of this study is to show that a dose of vitamin D3 higher than the recommended allowance may slow the cognitive decline of patients with a memory complaint.

Official Title
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Effect of Vitamin D on Cognitive Decline of Patients With Memory Complaint

Conditions
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Memory Disorders, Age-Related Cognitive Decline

Intervention / Treatment
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* Drug: Cholecalciferol 100 000 UI
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Pre-Inclusion Criteria : Patients aged 60 years or older, Who report to a memory centre with symptoms of memory complaint, Having a Mini-Mental State Examination (MMSE) score strictly > the 5th percentile for sociocultural level of the patient (GRECO standards for elderly patients), Having visual, hearing abilities (authorized equipment) and an oral or written expression sufficient for the suitable realization of the tests, Who accept participation in the study and are able to sign the informed consent of the - Affiliated to the French social security system. Inclusion Criteria: Insufficient 25 OH D serum level : 25 OH D < 50 nmol/L (20 ng/ml), Normal corrected plasma calcium concentration, Normal kidney function (cockcroft > 30 mL/mn) Exclusion Criteria: Alzheimer's disease or other dementia, Parkinson's disease treated, Epilepsy treated, Huntington's disease, Brain tumor, History of a progressive disease which may have consequences for the central nervous system (blood pressure, higher or equal to 180/100 mmHg, chronic pulmonary disease with hypoxia; cerebrovascular accident of less than 3 months, cranial traumatism with persistent neurologic deficit, subdural hematoma, brain surgery), Antecedent of alcoholism or chronic drug-addiction with an obvious or documented consequence on cognition, Severe depression : score Montgomery Asberg Depression Rating Scale (MADRS) > 18, Psychotropic drug therapy (at the discretion of the clinician), Hypercalcaemia or treatment for a hypercalcaemia, Known hypersensitivity to the vitamin D, Granulomatous disease, Treatment of vit D at doses higher than the current recommendations, History of calcium urinary lithiasis of less than 1 year, Nonsteroidal antiinflammatory drug (NSAID) chronic treatment, Severe medical or surgical affection of less than 3 months, Unstable health, severe hepatic or renal deficiency, Deprivation of liberty, under judicial protection, Institutionalization (EHPAD), Illiteracy, Participation in another biomedical research. A diagnosis of MCI (Mild Cognitive Impairment) of less than 6 months is not a criterion of non-inclusion.

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cholecalciferol 100 000 UI (Unité Internationale)<br>Oral solution in single-dose : 100 000 UI per month | Drug: Cholecalciferol 100 000 UI<br>* Study of superiority between Cholecalciferol high dose 100 000 UI versus placebo : one bulb per month during two years<br>* Other names: Uvedose;|
| Placebo Comparator: Placebo<br>Oral solution in single-dose per month | Drug: Placebo<br>* Study of superiority between Cholecalciferol high dose 100 000 UI versus placebo : one bulb per month during two years<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from baseline memory functions measured by the score of the total recall test from Free and Cued Selective Recall Reminding Test (Rappel Libre / Rappel Indicé 16 items : RL/RI 16) at one year and at two years | The score of the total recall test from Free and Cued Selective Recall Reminding Test (RL/RI 16) is recommended by a European Task Force consensus. | Baseline (at inclusion), one year and two years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from baseline global efficiency measured by the Mc Nair scale at one year and at two years |  | Baseline (inclusion), one year and two years | 
| Evolution of anaemia evaluated by red blood cells count |  | Baseline (pre-inclusion), one year and two years | 
| Evolution of plasma calcium and albumin concentration |  | Baseline (pre-inclusion), 45 days, one year and two years | 
| Evolution of urinary calcium and creatinine concentration |  | 45 days, one year and two years | 
| All adverse events |  | Up to two years | 
| Serum level of 25-hydroxy vitamine D (25-OH D) measured to study observance |  | Baseline (pre-inclusion), one year and two years | 
| Changes from baseline global efficiency measured by the Mini Mental State Examination at one year and at two years |  | Baseline (at inclusion), one year and two years | 
| Changes from baseline global efficiency measured by the Montreal Cognitive Assessment at one year and at two years |  | Baseline (at inclusion), one year and two years | 
| Changes from baseline instrumental activity of daily living measured by 8 items at one year and at two years |  | Baseline (at inclusion), one year and two years | 
| Changes from baseline language measured by the test de denomination orale d'images (DO-80) at one year and at two years |  | Baseline (at inclusion), one year and two years | 
| Memory function measured by a visual test : delayed matching to sample 48 items (DMS-48) |  | Baseline at inclusion | 
| Changes from baseline executive functions measured by the stroop test at one year and at two years |  | Baseline (at inclusion), one year and two years | 
| Changes from baseline executive functions measured by the verbal fluency at one year and at two years |  | Baseline (at inclusion), one year and two years | 
| Changes from baseline executive functions measured by the Trail Making Test part B at one year and at two years |  | Baseline (at inclusion), one year and two years | 
| Changes from baseline attention and speed processing measured by the Trail Making Test part A at one year and at two years |  | Baseline (at inclusion), one year and two years | 
| Changes from baseline attention and speed processing measured by the Digit symbol test at one year and at two years |  | Baseline (at inclusion), one year and two years | 
| Changes from baseline visuospatial study measured by the Rey figure (copy) at one year and at two years |  | Baseline (at inclusion), one year and two years | 
| Changes from baseline praxis at one year and at two years | Production of symbolic gesture, imitation utilization gesture, non sense gesture imitation | Baseline (at inclusion), one year and two years | 
| Changes from baseline depressive symptoms measured by the Montgomery and Asberg Depression Rating Scale at one year and at two years |  | Baseline (at inclusion), one year and two years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vitamin D, Cholecalciferol, 25-hydroxyvitamin D, Memory complaint, Subjective memory complaint, Mild cognitive impairment, Preventive therapy, Cognitive disorders