Dementia
Conditions
Keywords
Alzheimer's disease, Cholinesterase inhibitor, Discontinuation
Brief 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). 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.
Interventions
This group receives a half-dose of their previous cholinesterase inhibitor medication (in overencapsulated form) for two weeks, then receives placebo.
DRUGSham discontinuation
This group receives their previous dose of cholinesterase inhibitor medication, but in overencapsulated form
Sponsors
VA Office of Research and Development
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Successful Completion | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Caregiver Burden | 6 weeks | 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. |
| Veteran Cognition | 6 weeks | Six-Item Screener is a telephone-based assessment of cognitive status. The score ranges from 0 to 6. A higher score indicates better cognition. |
| Veteran Functioning | 6 weeks | 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. |
| Behavioral Symptoms | 6 weeks | 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. |
| Post-study Treatment Choice | 12 weeks | 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. |
Countries
United States
Participant flow
Recruitment details
Veterans who have received a prescription for a cholinesterase inhibitor for one year or greater.
Pre-assignment details
72 people were enrolled and consented, but only 61 were randomized.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 26 |
| 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. | 35 |
| Total | 61 |
Baseline characteristics
| Characteristic | Real Discontinuation | Sham Discontinuation | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 23 Participants | 33 Participants | 56 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 2 Participants | 5 Participants |
| Age, Continuous | 77.34 years STANDARD_DEVIATION 10.48 | 77.94 years STANDARD_DEVIATION 9.72 | 77.69 years STANDARD_DEVIATION 9.97 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 26 Participants | 34 Participants | 60 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | 25 Participants | 29 Participants | 54 Participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 25 Participants | 35 Participants | 60 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 26 | 1 / 35 |
| other Total, other adverse events | 9 / 26 | 3 / 35 |
| serious Total, serious adverse events | 0 / 26 | 0 / 35 |
Outcome results
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.
Time frame: 6 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Real Discontinuation | Successful Completion | 20 Participants |
| Sham Discontinuation | Successful Completion | 32 Participants |
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.
Time frame: 6 weeks
Population: Not all caregivers were willing to respond to all the items.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Real Discontinuation | Behavioral Symptoms | -1.63 score on a scale | Standard Deviation 6.26 |
| Sham Discontinuation | Behavioral Symptoms | -1.23 score on a scale | Standard Deviation 3.79 |
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.
Time frame: 6 weeks
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Real Discontinuation | Caregiver Burden | 5.58 Change in Zarit score | Standard Deviation 11.13 |
| Sham Discontinuation | Caregiver Burden | 1.66 Change in Zarit score | Standard Deviation 17.56 |
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.
Time frame: 12 weeks
Population: We were unable to reach some participants at 12 weeks.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Real Discontinuation | Post-study Treatment Choice | Participants not taking pre-study medication | 12 Participants |
| Real Discontinuation | Post-study Treatment Choice | Participants taking pre-study medication | 13 Participants |
| Sham Discontinuation | Post-study Treatment Choice | Participants taking pre-study medication | 25 Participants |
| Sham Discontinuation | Post-study Treatment Choice | Participants not taking pre-study medication | 7 Participants |
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.
Time frame: 6 weeks
Population: Some of the participants refused to complete the cognitive instrument over the phone.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Real Discontinuation | Veteran Cognition | -0.15 Change in Six-Item Screener Score | Standard Deviation 2.13 |
| Sham Discontinuation | Veteran Cognition | 0.13 Change in Six-Item Screener Score | Standard Deviation 0.9 |
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.
Time frame: 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Real Discontinuation | Veteran Functioning | -1.44 score on a scale | Standard Deviation 11.87 |
| Sham Discontinuation | Veteran Functioning | -0.59 score on a scale | Standard Deviation 6.72 |