Effect of Vitamin D on Cognitive Decline of Patients With Memory Complaint (D-COG)

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.

Study Overview

• Status: Completed
• Conditions: Memory Disorders; Age-Related Cognitive Decline
• Intervention / Treatment: Drug: Cholecalciferol 100 000 UI; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 68
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Angers, France, 49933
    • CHU Angers
  • Blois, France
    • CH Blois
  • Brest, France, 29200
    • CHU Brest - Hôpital de la Cavale Blanche
  • Elbeuf, France
    • CHI ELBEUF Louviers Val-de-Reuil
  • Nantes, France, 44093
    • CHU NANTES - Hôpital Laënnec
  • Nantes, France, 44093
    • CHU NANTES - Hôpital Bellier
  • Orléans, France, 45067
    • CHR Orléans
  • Poitiers, France, 86021
    • CHU Poitiers - Hôpital de La Milétrie
  • Rennes, France, 35064
    • CHU RENNES - Hôpital Hôtel Dieu
  • Rouen, France, 76031
    • CHU ROUEN - Hôpital Charles Nicolle
  • Tours, France, 37044
    • CHRU Tours - Hôpital Bretonneau

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Hospital, Tours
• Investigators: Principal Investigator: Fanny HENNEKINE, PH, CHRU Tours - Hôpital Bretonneau

Study record dates

Study Major Dates

• Study Start (Actual): October 23, 2014
• Primary Completion (Actual): October 10, 2018
• Study Completion (Actual): October 10, 2018

Study Registration Dates

• First Submitted: June 30, 2014
• First Submitted That Met QC Criteria: July 3, 2014
• First Posted (Estimate): July 9, 2014

Study Record Updates

• Last Update Posted (Actual): November 4, 2020
• Last Update Submitted That Met QC Criteria: November 3, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Vitamin D; 25-hydroxyvitamin D; Cholecalciferol; Mild cognitive impairment; Cognitive disorders; Preventive therapy; Memory complaint; Subjective memory complaint
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction; Memory Disorders; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol
• Other Study ID Numbers: SERC12-TC / D-COG; 2013-005110-36 (EudraCT Number)