Clinical trial NCT02248636: Cholinesterase Inhibitor Discontinuation
Official title: Cholinesterase Inhibitor Discontinuation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Dementia
Keywords: Alzheimer's disease
Cholinesterase inhibitor
Discontinuation
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2014-09-25
Enrollment: 72
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Successful Completion
timeFrame: 6 weeks
Secondary outcomes:
measure: Caregiver Burden
timeFrame: 6 weeks
measure: Veteran Cognition
timeFrame: 6 weeks
measure: Veteran Functioning
timeFrame: 6 weeks
measure: Behavioral Symptoms
timeFrame: 6 weeks
measure: Post-study Treatment Choice
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Central Arkansas VHS John L. McClellan Memorial Veterans Hospital, Little Rock, AR
state: Arkansas
city: Boise
country: United States
facility: Boise VA Medical Center, Boise, ID
state: Idaho
city: Bedford
country: United States
facility: Edith Nourse Rogers Memorial Veterans Hospital, Bedford, MA
state: Massachusetts
city: Seattle
country: United States
facility: VA Puget Sound Health Care System Seattle Division, Seattle, WA
state: Washington
Study officials:
affiliation: VA Puget Sound Health Care System Seattle Division, Seattle, WA
name: Stephen M Thielke, MD
role: PRINCIPAL_INVESTIGATOR
References: