Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Real discontinuation | Experimental | This group is tapered off their previous cholinesterase inhibitor medication. |
|
| Sham discontinuation | Sham Comparator | This group receives their previous cholinesterase inhibitor medication, but in in placebo form. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cholinesterase inhibitor | Drug | This group receives a half-dose of their previous cholinesterase inhibitor medication (in overencapsulated form) for two weeks, then receives placebo. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 6 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 6 weeks |
| Veteran Cognition |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Stephen M Thielke, MD | VA Puget Sound Health Care System Seattle Division, Seattle, WA | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Central Arkansas VHS John L. McClellan Memorial Veterans Hospital, Little Rock, AR | Little Rock | Arkansas | 72205-5484 | United States | ||
Not provided
Not provided
Not provided
Not provided
Not provided
72 people were enrolled and consented, but only 61 were randomized.
Veterans who have received a prescription for a cholinesterase inhibitor for one year or greater.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Real Discontinuation | This group is tapered off their previous cholinesterase inhibitor medication. Cholinesterase inhibitor: This group receives a half-dose of their previous cholinesterase inhibitor medication (in overencapsulated form) for two weeks, then receives placebo. |
| FG001 | Sham Discontinuation | This group receives their previous cholinesterase inhibitor medication, but in in placebo form. Sham discontinuation: This group receives their previous dose of cholinesterase inhibitor medication, but in overencapsulated form |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Real Discontinuation | This group is tapered off their previous cholinesterase inhibitor medication. Cholinesterase inhibitor: This group receives a half-dose of their previous cholinesterase inhibitor medication (in overencapsulated form) for two weeks, then receives placebo. |
| BG001 | Sham Discontinuation |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Count of Participants | Participants | 6 weeks |
|
Six weeks.
Dementia patients have a variety of behavioral and health events, which may fluctuate over time. We considered adverse events to be novel medical events differing from baseline.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Real Discontinuation | This group is tapered off their previous cholinesterase inhibitor medication. Cholinesterase inhibitor: This group receives a half-dose of their previous cholinesterase inhibitor medication (in overencapsulated form) for two weeks, then receives placebo. |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Behavior | Psychiatric disorders | Non-systematic Assessment | Behavior changed significantly |
The study was designed to allow participants to stop the study medication at any time, and for any reason. This is different than administrative withdrawal.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| William Banks, Associate Chief of Staff for Research | Puget Sound VA | 206 764-2701 | william.banks4@va.gov |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 2, 2019 | Sep 28, 2020 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 8, 2014 | Sep 28, 2020 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D003704 | Dementia |
| D000544 | Alzheimer Disease |
| ID | Term |
|---|---|
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D019965 | Neurocognitive Disorders |
Not provided
Not provided
| ID | Term |
|---|---|
| D002800 | Cholinesterase Inhibitors |
| ID | Term |
|---|---|
| D004791 | Enzyme Inhibitors |
| D045504 | Molecular Mechanisms of Pharmacological Action |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Sham discontinuation | Drug | This group receives their previous dose of cholinesterase inhibitor medication, but in overencapsulated form |
|
Six-Item Screener is a telephone-based assessment of cognitive status. The score ranges from 0 to 6. A higher score indicates better cognition.
| 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. | 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. | 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. | 12 weeks |
| Boise VA Medical Center, Boise, ID |
| Boise |
| Idaho |
| 83702 |
| United States |
| Edith Nourse Rogers Memorial Veterans Hospital, Bedford, MA | Bedford | Massachusetts | 01730 | United States |
| VA Puget Sound Health Care System Seattle Division, Seattle, WA | Seattle | Washington | 98108 | United States |
This group receives their previous cholinesterase inhibitor medication, but in in placebo form. Sham discontinuation: This group receives their previous dose of cholinesterase inhibitor medication, but in overencapsulated form. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
|
|
| Secondary | 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. | Not all of the caregivers completed the instrument. Some were unavailable after study enrollment. Some had a change in caregiver. Some refused to respond to all of the questions, since the instrument is rather lengthy. | Posted | Mean | Standard Deviation | Change in Zarit score | 6 weeks |
|
|
|
| Secondary | 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. | Some of the participants refused to complete the cognitive instrument over the phone. | Posted | Mean | Standard Deviation | Change in Six-Item Screener Score | 6 weeks |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | score on a scale | 6 weeks |
|
|
|
| Secondary | 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. | Not all caregivers were willing to respond to all the items. | Posted | Mean | Standard Deviation | score on a scale | 6 weeks |
|
|
|
| Secondary | 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. | We were unable to reach some participants at 12 weeks. | Posted | Count of Participants | Participants | 12 weeks |
|
|
|
| 0 |
| 26 |
| 0 |
| 26 |
| 9 |
| 26 |
| EG001 | Sham Discontinuation | This group receives their previous cholinesterase inhibitor medication, but in in placebo form. Sham discontinuation: This group receives their previous dose of cholinesterase inhibitor medication, but in overencapsulated form | 1 | 35 | 0 | 35 | 3 | 35 |
Not provided
Not provided
Not provided
| D001523 | Mental Disorders |
| D024801 | Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D018678 | Cholinergic Agents |
| D018377 | Neurotransmitter Agents |
| D045505 | Physiological Effects of Drugs |