Discontinuation of Cholinesterase Inhibitors for the Treatment of Severe Alzheimer's Disease

Summary

There are few pharmacological treatments available for Alzheimer's disease, including drugs called cholinesterase inhibitors: donepezil, galantamine, and rivastigmine. In research trials, cholinesterase inhibitors have been shown to improve memory and problem behaviours in people with mild to moderate Alzheimer's disease. However, these benefits may not extend to the real-world when taking into account nursing home and health care costs. There is less information on the use of cholinesterase inhibitors in people with severe Alzheimer's disease. In Canada, only donepezil is recommended for the treatment of severe Alzheimer's disease. However, there is no information on whether the benefits that donepezil provides to people with severe Alzheimer's disease are sustained over the long term. Moreover, while the tolerability of cholinesterase inhibitors is generally acceptable, their use is not completely harmless. Common side effects include nausea, diarrhea, insomnia, vomiting, muscle cramping, fatigue and loss of appetite.

In Ontario, cholinesterase inhibitor users tend to remain on these medications for two years or more and often until death. The current cholinesterase inhibitor guidelines provide details on what medication should be used, when it should be started and how it should be monitored, but there is less clarity on when it is safe and appropriate to stop treatment. The cessation of cholinesterase inhibitors in patients no longer appearing to display any clear benefits may help to lower the risk of unpleasant side effects, lower the use of multiple medications, and reduce the costs of caring for individuals with Alzheimer's disease. However, the cessation of cholinesterase inhibitor therapy may run the risk of deterioration in memory, worsening or development of behavioural symptoms and the placement of additional demands on professional and unpaid caregivers.

There is a clear need for guidelines when to stop cholinesterase inhibitor treatment, especially for patients in whom the benefits of not be on the medication will outweigh the risks. The purpose of this study is to address this issue by collecting data which may be helpful in predicting which types of patients may benefit from stopping cholinesterase inhibitor treatment. Understanding when, and for whom, it is appropriate to stop cholinesterase inhibitor treatment will influence the field of pharmacology in the treatment of Alzheimer's disease.

Conditions

• Alzheimer's Disease
• Dementia

Interventions

DRUG

Cholinesterase Inhibitor

For participants randomized into the active treatment arm, they will be provided with the following study medications: Donepezil - 5 mg or 10 mg Galantamine - 8 mg and 16 mg and 24 mg Rivastigmine - 1.5 mg and 3 mg The type of study medication provided will depend on the type and dosage of the cholinesterase inhibitor they have been receiving for the last 3 months of their regular treatment. For example, if that have been taking Donepezil - 5 mg daily, they will continue on that same medication, dosage and frequency.

DRUG

Placebo

For participants randomized into the placebo intervention, placebo capsules will match capsules in the active intervention.

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre

  lead OTHER

Principal Investigators

• Krista L. Lanctôt, PhD · Sunnybrook Research Institute

• Nathan Herrmann, MD · Sunnybrook Health Sciences Centre

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

55 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2010-07-31

Primary Completion

2014-05-31

Completion

2015-09-30

Countries

• Canada

Study Locations