Alzheimer's Disease - Input of Vitamin D With mEmantine Assay - Full Text View

Purpose

The purpose of this study is to compare the effect after 24 weeks of the oral intake of vitamin D3 (cholecalciferol) with the effect of a placebo on the change of cognitive performance in patients suffering from moderate Alzheimer's disease or related disorders (ADRD) and receiving memantine.

Condition	Intervention	Phase
Alzheimer Disease	Drug: Memantine Drug: Vitamin D Drug: Vitamin D placebo	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Evaluation d'Une stratégie thérapeutique d'Association médicamenteuse Pour la Prise en Charge de la Maladie d'Alzheimer et Des Maladies apparentées au Stade modéré

Resource links provided by NLM:

Genetics Home Reference related topics: Alzheimer disease

MedlinePlus related topics: Alzheimer's Disease Vitamin D

Drug Information available for: Cholecalciferol Vitamin D Memantine Memantine hydrochloride

U.S. FDA Resources

Further study details as provided by University Hospital, Angers:

Primary Outcome Measures:

Change in cognitive performance [ Time Frame: This outcome is assessed at baseline, 12 and 24 weeks after inclusion ] [ Designated as safety issue: No ]
Cognitive performance is measured with Alzheimer's Disease Assessment Scale-cognition score (ADAS-cog)

Secondary Outcome Measures:

Change in other cognitive scores [ Time Frame: This outcome is assessed at baseline, 12 and 24 weeks after inclusion ] [ Designated as safety issue: No ]
MMSE, Cognitive Assessment Battery, Frontal Assessment Battery, Trail Making Test parts A and B
Change in functional performance [ Time Frame: This outcome is assessed at baseline, 12 and 24 weeks after inclusion ] [ Designated as safety issue: No ]
Activities of Daily Living scale and 4-item Instrumental Activities of Daily Living scale
Change in posture and gait [ Time Frame: This outcome is assessed at baseline, 12 and 24 weeks after inclusion ] [ Designated as safety issue: No ]
Timed Up & Go, Five Time Sit-to-Stand and spatio-temporal analysis of walking
Between-group comparison of compliance to treatment and tolerance [ Time Frame: This outcome is assessed at baseline, 12 and 24 weeks after inclusion ] [ Designated as safety issue: Yes ]
These outcomes are assessed together with the serum concentrations of 25OHD, calcium and parathyroid hormone.

Estimated Enrollment:	120
Study Start Date:	September 2011
Estimated Study Completion Date:	February 2013
Estimated Primary Completion Date:	February 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Intervention All participants start the treatment with memantine on the first day of the study and immediately start vitamin D supplementation.	Drug: Memantine Memantine is administered to all participants according to the usual strategy, with upward titration of 5 mg per week during the first three weeks to reduce the risk of side effects. The final dosage is 20 mg per day, with no subsequent modification of dosage or specialty during the trial. Other Name: Chlorhydrate de mémantine (Ebixa®) Drug: Vitamin D Subjects receive Vitamin D supplementation (cholecalciferol 100,000 IU, drinking solution, 2 mL vial) at a rate of 1 drinking vial of 100,000 IU cholecalciferol every month. In brief, the total dose is 600,000 IU over the duration of the study starting with one vial at the time of inclusion, then at week(W) 4, W8, W12, W16 and W20. The dose of vitamin D supplementation will not be adjusted except in case of an adverse event such as hypercalcemia. In this case, vitamin D supplementation is stopped and the participant is released prematurely from the study. Other Name: Colecalciferol
Placebo Comparator: Placebo Participants in this arm start the treatment with memantine in the same way as the 'Intervention' group. They also immediately start Vitamin D placebo administered at the same pace.	Drug: Memantine Memantine is administered to all participants according to the usual strategy, with upward titration of 5 mg per week during the first three weeks to reduce the risk of side effects. The final dosage is 20 mg per day, with no subsequent modification of dosage or specialty during the trial. Other Name: Chlorhydrate de mémantine (Ebixa®) Drug: Vitamin D placebo Subjects receive Vitamin D placebo (drinking solution, 2mL vial) at a rate of 1 drinking vial every month. In brief, the subjects start with one vial at the time of inclusion, then at week(W)4, W8, W12, W16 and W20. The placebo drinking solution contains all the excipients present in the Vitamin D vial. Other Name: Placebo

Arms

Assigned Interventions

Active Comparator: Intervention

All participants start the treatment with memantine on the first day of the study and immediately start vitamin D supplementation.

Drug: Memantine

Memantine is administered to all participants according to the usual strategy, with upward titration of 5 mg per week during the first three weeks to reduce the risk of side effects. The final dosage is 20 mg per day, with no subsequent modification of dosage or specialty during the trial.

Other Name: Chlorhydrate de mémantine (Ebixa®)

Drug: Vitamin D

Subjects receive Vitamin D supplementation (cholecalciferol 100,000 IU, drinking solution, 2 mL vial) at a rate of 1 drinking vial of 100,000 IU cholecalciferol every month. In brief, the total dose is 600,000 IU over the duration of the study starting with one vial at the time of inclusion, then at week(W) 4, W8, W12, W16 and W20. The dose of vitamin D supplementation will not be adjusted except in case of an adverse event such as hypercalcemia. In this case, vitamin D supplementation is stopped and the participant is released prematurely from the study.

Other Name: Colecalciferol

Placebo Comparator: Placebo

Participants in this arm start the treatment with memantine in the same way as the 'Intervention' group. They also immediately start Vitamin D placebo administered at the same pace.

Drug: Memantine

Memantine is administered to all participants according to the usual strategy, with upward titration of 5 mg per week during the first three weeks to reduce the risk of side effects. The final dosage is 20 mg per day, with no subsequent modification of dosage or specialty during the trial.

Other Name: Chlorhydrate de mémantine (Ebixa®)

Drug: Vitamin D placebo

Subjects receive Vitamin D placebo (drinking solution, 2mL vial) at a rate of 1 drinking vial every month. In brief, the subjects start with one vial at the time of inclusion, then at week(W)4, W8, W12, W16 and W20. The placebo drinking solution contains all the excipients present in the Vitamin D vial.

Other Name: Placebo

Detailed Description:

Current treatments for Alzheimer's disease and related disorders (ADRD) are symptomatic and can only temporarily slow down ADRD. Future possibilities of care could rely on multi-target drugs therapies that address simultaneously several pathophysiological processes leading to neurodegeneration. We hypothesized that the combination of memantine with vitamin D could be neuroprotective in ADRD, thereby limiting neuronal loss and cognitive decline.

The primary objective of this trial is to compare the effect after 24 weeks of the oral intake of vitamin D3 with the effect of a placebo on the evolution of cognitive performance in patients suffering from moderate ADRD and receiving memantine.

The secondary objectives of the study are as follows:

To compare the effect after 12 weeks of the oral intake of vitamin D3 with the effect of a placebo on the evolution of cognitive performance in patients suffering from moderate ADRD and receiving memantine.
To compare the effect after 12 and 24 weeks of the oral intake of vitamin D3 with the effect of a placebo on the evolution of functional abilities in patients suffering from moderate ADRD and receiving memantine.
To compare the effect after 12 and 24 weeks of the oral intake of vitamin D3 with the effect of a placebo on the evolution of postural and gait performance in patients suffering from moderate ADRD and receiving memantine.
To determine the compliance to treatment and tolerance of the oral intake of vitamin D3 in patients suffering from moderate ADRD and receiving memantine.

Eligibility

Ages Eligible for Study:	60 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age ≥ 60 years
Diagnosis of moderate Alzheimer's disease or related disorders (DSM-IV/NINCDSADRDA) with a score of Mini-Mental State Examination (MMSE) between 10 and 20 inclusively
To have hypovitaminosis D (i.e., serum 25-hydroxyvitamin D [25OHD]concentration < 30 ng/mL)
To have no hypercalcemia (defined as serum calcium concentration ≥ 2,65 mmol/L)
To have given and signed an informed consent form to participate in the trial (or informed consent form obtained from the trusted person or legal representative, as appropriate)
To be affiliated to French Social Security

Exclusion Criteria:

The use of standard antidementia drugs (i.e., anticholinesterasics, memantine, or vasodilatators) in the past 60 days
Severe hepatic or renal failure
Severe, unstable or poorly controlled medical conditions at the time of the inclusion
Other cognitive disorders (untreated dysthyroid, deficiency in vitamin B9 or B12, chronic ongoing ethylism, history of syphilis, stroke, delirium revealed with the Confusion Assessment Method (CAM), severe depressive symptomatology (Geriatric Depression score ≥ 10/15))
Contra-indications to memantine or vitamin D
Enrollment in another simultaneous clinical trial

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01409694

Contacts

Contact: Cédric Annweiler, MD, PhD

++33 2 41 35 54 86

ceannweiler@chu-angers.fr

Locations

France
University Hospital	Recruiting
Angers, France, 49933
Contact: Cédric Annweiler, MD, PhD ++33 2 41 35 54 86 ceannweiler@chu-angers.fr

Sponsors and Collaborators

University Hospital, Angers

Investigators

Principal Investigator:

Cédric Annweiler, MD, PhD

Angers University Hospital

More Information

No publications provided by University Hospital, Angers

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Annweiler C, Fantino B, Parot-Schinkel E, Thiery S, Gautier J, Beauchet O. Alzheimer's disease--input of vitamin D with mEmantine assay (AD-IDEA trial): study protocol for a randomized controlled trial. Trials. 2011 Oct 20;12:230.

Responsible Party:	Cedric Annweiler, MD, PhD, Angers University Hospital
ClinicalTrials.gov Identifier:	NCT01409694 History of Changes
Other Study ID Numbers:	2010-024506-35
Study First Received:	August 2, 2011
Last Updated:	October 10, 2011
Health Authority:	France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) France: Committee for the Protection of Personnes France: The Commission nationale de l’informatique et des libertés France: Institutional Ethical Committee

Keywords provided by University Hospital, Angers:

Alzheimer Disease
Vitamin D
Cholecalciferol
Memantine
Cognition Disorders

Additional relevant MeSH terms:

Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Cholecalciferol
Vitamin D
Ergocalciferols
Vitamins
Memantine

Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Bone Density Conservation Agents
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 16, 2013

Alzheimer's Disease - Input of Vitamin D With mEmantine Assay (AD-IDEA)