DementiaPhase 2/3CIDNCT02248636
Cholinesterase Inhibitor Discontinuation
A Phase 2/3 study testing Cholinesterase inhibitor in people with Dementia, run by VA Office of Research and Development at 4 sites in United States.
Trial summary
This study tries to determine if stopping certain medications that are used to treat dementia will cause worsening from the patient and family perspective. All of the participants will take pills that look identical, and that may contain active drug or an inactive pill (a placebo). Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Dementia
- What is being tested?
- Cholinesterase inhibitor
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 72 participants
- Where
- 4 sitesUnited States
- Study dates
- 22 Jan 2015to 1 Oct 2019
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males and females ages 60 and older.
- Taking stable dose of donepezil 10mg or greater per day, or galantamine 8mg or greater per day, for at least 1 year.
- Presence of a primary caregiver who can assume responsibility for medication compliance, OR residence in a nursing home with a staff member who can provide information.
- Primary care visit within last 12 months.
- Willing to have the CI medication discontinued.
Who cannot join
- Terminal medical condition for which life expectancy would be less than 6 months.
- Parkinson's Disease
- Presence of any uncontrolled systemic illness that would interfere with participation in the study.
- Unstable medical condition.
- Receiving services from hospice.
- Current prescription with more than one CI
- Receiving medication in an investigational drug study.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Edith Nourse Rogers Memorial Veterans Hospital, Bedford, MA
Bedford, Massachusetts, 01730
Boise VA Medical Center, Boise, ID
Boise, Idaho, 83702
Central Arkansas VHS John L. McClellan Memorial Veterans Hospital, Little Rock, AR
Little Rock, Arkansas, 72205-5484
VA Puget Sound Health Care System Seattle Division, Seattle, WA
Seattle, Washington, 98108
About this study
This study tries to determine if stopping certain medications that are used to treat dementia will cause worsening from the patient and family perspective.
All of the participants will take pills that look identical, and that may contain active drug or an inactive pill (a placebo). Half of the group will receive the same treatment they were taking before the study -- this is called the "sham discontinuation" arm. The other half will receive a reduced dose of their medication, and then an inactive pill (placebo) -- this is called the "real discontinuation" arm.
Participants will be able to return to their previous dose of medication at any time during the study. The percentage of people who return will be measured and compared. Other medical events and factors such as behaviors, thinking, and caregiver distress, will be measured and compared between the groups.
Read the detailed description
There are no reliable findings from controlled trials about discontinuation of cholinesterase inhibitors from a patient and family perspective. It is unknown at what point these medications do not have effects, and how they can safely be discontinued.
The investigators will identify Veterans who have been taking a cholinesterase inhibitor (CI) (donepezil or galantamine) for at least one year. After informed consent, the investigators will randomize them to Real Taper (half-dose of the CI they had taken for 3 weeks, then placebo for 3 weeks), or Sham Taper (continued full dose of the CI they had taken for 6 weeks). The pills will be blinded by over-encapsulating of the drug or placebo.
An intake interview will ascertain history and measure behaviors, cognitive symptoms, and mood, as well as caregiver burden. Phone calls will assess treatment use and adverse events at week 2 and week 4. An exit interview at week 6 will measure the same variables as at baseline. Participants will be unblinded at that point so they will know which treatment had been used. A follow-up call at 12 weeks will ascertain ongoing treatment and any further adverse events.
At any point in the study, participants and caregivers will be able to return to their pre-study dose of medication.
The primary outcome is the percentage of participants who successfully complete a 6-week discontinuation. This will be compared between arms. Other outcomes related to medical events (e.g. hospitalizations, falls), symptoms (e.g. cognition, behaviors), and caregiver distress will be measured and compared.
- Conditions
- Dementia
- Being tested
- Cholinesterase inhibitor, Sham discontinuation
- Keywords
- Alzheimer's disease, Cholinesterase inhibitor, Discontinuation
- Medical subject headings
- Dementia, Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cholinesterase inhibitorDrug
This group receives a half-dose of their previous cholinesterase inhibitor medication (in overencapsulated form) for two weeks, then receives placebo.
Sham discontinuationDrug
This group receives their previous dose of cholinesterase inhibitor medication, but in overencapsulated form
| Study group | Role | What they receive |
|---|---|---|
| Real discontinuation | Experimental | This group is tapered off their previous cholinesterase inhibitor medication. Receives: Drug: Cholinesterase inhibitor |
| Sham discontinuation | Sham comparator | This group receives their previous cholinesterase inhibitor medication, but in in placebo form. Receives: Drug: Sham discontinuation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Successful Completion
Participants can return to their pre-study dose of medication at any time. If they complete 6 weeks of either real discontinuation or sham discontinuation, they are considered to have successfully completed treatment.
Measured: 6 weeks
Secondary outcomes (5)
Caregiver Burden
The Zarit Caregiver Burden Interview contains 22 items, each on a 5-point scale, for a maximum score of 110. The minimum score is 0. A higher score indicates worse subjective burden.
Measured: 6 weeks
Veteran Cognition
Six-Item Screener is a telephone-based assessment of cognitive status. The score ranges from 0 to 6. A higher score indicates better cognition.
Measured: 6 weeks
Veteran Functioning
The Alzheimer's Disease Cooperative Study ADL Scale (ADCS-ADL) is a 23-item scale divided into activities of daily living and independent activities of daily living. Scores range from 0-78. A lower score indicates worse functional ability.
Measured: 6 weeks
Behavioral Symptoms
The Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD) is a 25-item instrument. Scores range from 0-75, with a higher number indicating worse behavioral symptoms.
Measured: 6 weeks
Post-study Treatment Choice
Veteran and caregiver decision to continue, or to have restarted, the pre-study medication at 12 weeks. The participants were unblinded at 6 weeks, and were requested to make their own decision about restarting.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2014 (estimated)
- Study start22 Jan 2015
- Primary completion1 Oct 2019
- Study completion1 Oct 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for DementiaStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 72 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Stephen M Thielke, MD, Principal investigator, VA Puget Sound Health Care System Seattle Division, Seattle, WA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02248636
- Sponsor's protocol ID
- CLIN-014-13F
- Acronym
- CID
- Status last verified
- Sep 2020
- First submitted
- 22 Sep 2014
- Last updated
- 23 Oct 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cholinesterase Inhibitor Discontinuation
- ClinicalTrials.gov ID
- NCT02248636
- Acronym / sponsor ID
- CID / CLIN-014-13F
- Conditions
- Dementia
- Keywords
- Alzheimer's disease, Cholinesterase inhibitor, Discontinuation
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 72 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- 22 Jan 2015 (actual)
- Primary completion
- 1 Oct 2019 (actual)
- Study completion
- 1 Oct 2019 (actual)
- First posted
- 25 Sep 2014 (estimated)
- Results
- Posted 23 Oct 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study tries to determine if stopping certain medications that are used to treat dementia will cause worsening from the patient and family perspective.
All of the participants will take pills that look identical, and that may contain active drug or an inactive pill (a placebo). Half of the group will receive the same treatment they were taking before the study -- this is called the "sham discontinuation" arm. The other half will receive a reduced dose of their medication, and then an inactive pill (placebo) -- this is called the "real discontinuation" arm.
Participants will be able to return to their previous dose of medication at any time during the study. The percentage of people who return will be measured and compared. Other medical events and factors such as behaviors, thinking, and caregiver distress, will be measured and compared between the groups.
Detailed description
There are no reliable findings from controlled trials about discontinuation of cholinesterase inhibitors from a patient and family perspective. It is unknown at what point these medications do not have effects, and how they can safely be discontinued.
The investigators will identify Veterans who have been taking a cholinesterase inhibitor (CI) (donepezil or galantamine) for at least one year. After informed consent, the investigators will randomize them to Real Taper (half-dose of the CI they had taken for 3 weeks, then placebo for 3 weeks), or Sham Taper (continued full dose of the CI they had taken for 6 weeks). The pills will be blinded by over-encapsulating of the drug or placebo.
An intake interview will ascertain history and measure behaviors, cognitive symptoms, and mood, as well as caregiver burden. Phone calls will assess treatment use and adverse events at week 2 and week 4. An exit interview at week 6 will measure the same variables as at baseline. Participants will be unblinded at that point so they will know which treatment had been used. A follow-up call at 12 weeks will ascertain ongoing treatment and any further adverse events.
At any point in the study, participants and caregivers will be able to return to their pre-study dose of medication.
The primary outcome is the percentage of participants who successfully complete a 6-week discontinuation. This will be compared between arms. Other outcomes related to medical events (e.g. hospitalizations, falls), symptoms (e.g. cognition, behaviors), and caregiver distress will be measured and compared.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Real discontinuation | Experimental | Drug: Cholinesterase inhibitorThis group is tapered off their previous cholinesterase inhibitor medication. |
| Sham discontinuation | Sham comparator | Drug: Sham discontinuationThis group receives their previous cholinesterase inhibitor medication, but in in placebo form. |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Males and females ages 60 and older.
- Taking stable dose of donepezil 10mg or greater per day, or galantamine 8mg or greater per day, for at least 1 year.
- Presence of a primary caregiver who can assume responsibility for medication compliance, OR residence in a nursing home with a staff member who can provide information.
- Primary care visit within last 12 months.
- Willing to have the CI medication discontinued.
Key exclusion criteria (7 listed)
- Terminal medical condition for which life expectancy would be less than 6 months.
- Parkinson's Disease
- Presence of any uncontrolled systemic illness that would interfere with participation in the study.
- Unstable medical condition.
- Receiving services from hospice.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cholinesterase inhibitorThis group receives a half-dose of their previous cholinesterase inhibitor medication (in overencapsulated form) for two weeks, then receives placebo. | Drug | Real discontinuation |
| Sham discontinuationThis group receives their previous dose of cholinesterase inhibitor medication, but in overencapsulated form | Drug | Sham discontinuation |
Primary outcome
Successful Completion
Time frame: 6 weeks
Participants can return to their pre-study dose of medication at any time. If they complete 6 weeks of either real discontinuation or sham discontinuation, they are considered to have successfully completed treatment.
5 secondary outcomes
Caregiver Burden
Time frame: 6 weeks
Veteran Cognition
Time frame: 6 weeks
Veteran Functioning
Time frame: 6 weeks
Behavioral Symptoms
Time frame: 6 weeks
Post-study Treatment Choice
Time frame: 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Oct 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stephen M Thielke, MD principal investigator
VA Puget Sound Health Care System Seattle Division, Seattle, WA
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Cholinesterase inhibitor in people with Dementia, run by VA Office of Research and Development at 4 sites in United States.
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 5 inclusion and 7 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 23 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. 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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Yes. Results are posted in the registry (first posted 23 Oct 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Successful Completion (time frame: 6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 23 Oct 2020.