AzTrials
AzTrials

Alzheimer's DiseasePhase 3NCT02035982

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

A Phase 3 study testing Cholinesterase Inhibitor in people with Alzheimer's Disease and Dementia, run by Sunnybrook Health Sciences Centre at 2 sites in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 55 years and older
Conditions the study is for
Alzheimer's Disease, Dementia
What is being tested?
Cholinesterase Inhibitor
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
40 participants
Where
2 sitesCanada
Study dates
Jul 2010to Sep 2015
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 55 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Aged >55 years
  • Meet Diagnostic and Statistical Manual - IV (DSM-IV) criteria for primary degenerative dementia
  • Meet National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for probable AD of at least one year's duration
  • Score ≤15 on the Mini-Mental State Examination (MMSE) (severe dementia)
  • Receiving donepezil (5 or 10 mg), galantamine (8, 16 or 24 mg) or rivastigmine (3, 4.5 or 6 mg oral) for at least 2 years, with a stable dose for at least 3 months prior to study entry
  • Patients with a current order for any regularly administered psychotropic (e.g. selective serotonin reuptake inhibitor (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), trazodone, atypical or typical antipsychotics) must have been on a stable dose for at least 1 month prior to study entry

Who cannot join

  • Patients with the following conditions will be excluded:
  • Dementia due to any etiology other than Alzheimer's Disease (AD)
  • Significant difficulty ingesting oral medications
  • Current evidence of any uncontrolled medical illness that would interfere with the subject's participation in the study

Trial locations and contacts

2 sites in 1 country.

Canada2 sites

  • North York General Hospital

    Toronto, Ontario, M2K1E1

  • Sunnybrook Health Sciences Centre

    Toronto, Ontario, M4N 3M5

Other trials in Canada

About this study

Official title: A Discontinuation of Cholinesterase Inhibitors for the Treatment of Severe Alzheimer's Disease in Long Term Care Setting

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.

Being tested
Cholinesterase Inhibitor, Placebo
Medical subject headings
Alzheimer Disease, Dementia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Cholinesterase InhibitorDrug

    Also called Galantamine, Donepezil, Rivastigmine

    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.

  • PlaceboDrug

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

Study groups in NCT02035982
Study groupRoleWhat they receive
Cholinesterase InhibitorActive comparatorParticipants randomized into the cholinesterase inhibitor arm will continue receiving their cholinesterase inhibitor at the same dosage.
Receives: Drug: Cholinesterase Inhibitor
PlaceboPlacebo comparatorParticipants randomized into the placebo arm will be tapered off their cholinesterase inhibitor for the first 2 weeks. For the remaining 6 weeks of their study they will be receiving only placebo, and no cholinesterase inhibitor.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Clinician's Global Impression of Change (CGIC)

    CGIC score is used as a measure of clinically meaningful change, as distinct from an instrument's ability to assess any change. This scale is completed by the clinician.

    Measured: baseline (0 weeks), 4 and 8 weeks

Secondary outcomes (1)

  1. Number of total adverse events

    All emerging adverse events (AEs) will be noted and followed-up until resolution. The total number of adverse events within each intervention arm will be compared between groups.

    Measured: 2, 4, and 8 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Jan 2014 (estimated)
  2. Study startJul 2010
  3. Primary completionMay 2014
  4. Study completionSep 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02035982
Sponsor's protocol ID
107-2010
Other IDs
Grant #12-74
Status last verified
Apr 2017
First submitted
25 Nov 2013
Last updated
28 Apr 2017
Results posted
No
Data monitoring committee
No

Publications

  • Herrmann N, O'Regan J, Ruthirakuhan M, Kiss A, Eryavec G, Williams E, Lanctot KL. A Randomized Placebo-Controlled Discontinuation Study of Cholinesterase Inhibitors in Institutionalized Patients With Moderate to Severe Alzheimer Disease. J Am Med Dir Assoc. 2016 Feb;17(2):142-7. doi: 10.1016/j.jamda.2015.08.019. Epub 2015 Oct 9.

    PubMed 26482056

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Cholinesterase Inhibitor in people with Alzheimer's Disease and Dementia, run by Sunnybrook Health Sciences Centre at 2 sites in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Clinician's Global Impression of Change (CGIC) (time frame: baseline (0 weeks), 4 and 8 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02035982, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Apr 2017.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in