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

NCT ID: NCT01409694

Last Updated: 2016-09-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-09-30
• Study Completion Date: 2016-01-31

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.

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.

Conditions

Alzheimer Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Intervention

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

Group Type: ACTIVE_COMPARATOR

Memantine

Intervention Type: DRUG

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.

Vitamin D

Intervention Type: DRUG

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.

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.

Group Type: PLACEBO_COMPARATOR

Memantine

Intervention Type: DRUG

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.

Vitamin D placebo

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Chlorhydrate de mémantine (Ebixa®); Colecalciferol; Placebo

Eligibility 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

• Minimum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Angers

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Cédric Annweiler, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Angers University Hospital

Locations

University Hospital

Angers, , France

Countries

France

References

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.

Reference Type: DERIVED

PMID: 22233455 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 22014101 (View on PubMed)

Other Identifiers

2010-024506-35

Identifier Type: -

Identifier Source: org_study_id