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

• ClinicalTrials.gov Identifier: NCT01409694
• Recruitment Status: Completed
• First Posted: August 4, 2011
• Last Update Posted: September 22, 2016
• Sponsor: University Hospital, Angers
• Information provided by (Responsible Party): University Hospital, Angers

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Alzheimer Disease	Drug: Memantine; Drug: Vitamin D; Drug: Vitamin D placebo	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 90 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, 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
• Study Start Date: September 2011
• Actual Primary Completion Date: January 2016
• Actual Study Completion Date: January 2016

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

1. Change in cognitive performance [ Time Frame: This outcome is assessed at baseline, 12 and 24 weeks after inclusion ]
   Cognitive performance is measured with Alzheimer's Disease Assessment Scale-cognition score (ADAS-cog)

Secondary Outcome Measures :

1. Change in other cognitive scores [ Time Frame: This outcome is assessed at baseline, 12 and 24 weeks after inclusion ]
   MMSE, Cognitive Assessment Battery, Frontal Assessment Battery, Trail Making Test parts A and B
2. Change in functional performance [ Time Frame: This outcome is assessed at baseline, 12 and 24 weeks after inclusion ]
   Activities of Daily Living scale and 4-item Instrumental Activities of Daily Living scale
3. Change in posture and gait [ Time Frame: This outcome is assessed at baseline, 12 and 24 weeks after inclusion ]
   Timed Up & Go, Five Time Sit-to-Stand and spatio-temporal analysis of walking
4. Between-group comparison of compliance to treatment and tolerance [ Time Frame: This outcome is assessed at baseline, 12 and 24 weeks after inclusion ]
   These outcomes are assessed together with the serum concentrations of 25OHD, calcium and parathyroid hormone.

Eligibility Criteria

• Ages Eligible for Study: 60 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

Locations

France

University Hospital

Angers, France, 49933

Sponsors and Collaborators

University Hospital, Angers

Investigators

• Principal Investigator: Cédric Annweiler, MD, PhD; Angers University Hospital

More Information

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

Annweiler C, Beauchet O. Possibility of a new anti-alzheimer's disease pharmaceutical composition combining memantine and vitamin D. Drugs Aging. 2012 Feb 1;29(2):81-91. doi: 10.2165/11597550-000000000-00000. Review.

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. doi: 10.1186/1745-6215-12-230.

• Responsible Party: University Hospital, Angers
• ClinicalTrials.gov Identifier: NCT01409694
• Other Study ID Numbers: 2010-024506-35
• First Posted: August 4, 2011
• Last Update Posted: September 22, 2016
• Last Verified: March 2011

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; Neurocognitive Disorders; Mental Disorders; Vitamin D; Ergocalciferols; Vitamins; Memantine; Micronutrients; Physiological Effects of Drugs; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Dopamine Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents