MedPath

Cholinesterase Inhibitor Discontinuation

Phase 2
Completed
Conditions
Dementia
Interventions
Drug: Sham discontinuation
Drug: Cholinesterase inhibitor
Registration Number
NCT02248636
Lead Sponsor
VA Office of Research and Development
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
72
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.
Read More
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.
Read More

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Sham discontinuationSham discontinuationThis group receives their previous cholinesterase inhibitor medication, but in in placebo form.
Real discontinuationCholinesterase inhibitorThis group is tapered off their previous cholinesterase inhibitor medication.
Primary Outcome Measures
NameTimeMethod
Successful Completion6 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 Outcome Measures
NameTimeMethod
Behavioral Symptoms6 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.

Veteran Cognition6 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.

Caregiver Burden6 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 Functioning6 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.

Post-study Treatment Choice12 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.

Trial Locations

Locations (4)

Edith Nourse Rogers Memorial Veterans Hospital, Bedford, MA

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Bedford, Massachusetts, United States

Central Arkansas VHS John L. McClellan Memorial Veterans Hospital, Little Rock, AR

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Little Rock, Arkansas, United States

VA Puget Sound Health Care System Seattle Division, Seattle, WA

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Seattle, Washington, United States

Boise VA Medical Center, Boise, ID

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Boise, Idaho, United States

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