Cholinesterase Inhibitor Discontinuation (CID)

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.

Study Overview

• Status: Completed
• Conditions: Dementia
• Intervention / Treatment: Drug: Cholinesterase inhibitor; Drug: Sham discontinuation

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 Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205-5484
      • Central Arkansas VHS John L. McClellan Memorial Veterans Hospital, Little Rock, AR
  • Idaho
    • Boise, Idaho, United States, 83702
      • Boise VA Medical Center, Boise, ID
  • Massachusetts
    • Bedford, Massachusetts, United States, 01730
      • Edith Nourse Rogers Memorial Veterans Hospital, Bedford, MA
  • Washington
    • Seattle, Washington, United States, 98108
      • VA Puget Sound Health Care System Seattle Division, Seattle, WA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Real discontinuation; This group is tapered off their previous cholinesterase inhibitor medication.	Drug: Cholinesterase inhibitor; This group receives a half-dose of their previous cholinesterase inhibitor medication (in overencapsulated form) for two weeks, then receives placebo.
Sham Comparator: Sham discontinuation; This group receives their previous cholinesterase inhibitor medication, but in in placebo form.	Drug: Sham discontinuation; This group receives their previous dose of cholinesterase inhibitor medication, but in overencapsulated form

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Investigators: Principal Investigator: Stephen M Thielke, MD, VA Puget Sound Health Care System Seattle Division, Seattle, WA

Study record dates

Study Major Dates

• Study Start (Actual): January 22, 2015
• Primary Completion (Actual): October 1, 2019
• Study Completion (Actual): October 1, 2019

Study Registration Dates

• First Submitted: September 22, 2014
• First Submitted That Met QC Criteria: September 22, 2014
• First Posted (Estimate): September 25, 2014

Study Record Updates

• Last Update Posted (Actual): October 23, 2020
• Last Update Submitted That Met QC Criteria: September 29, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: Alzheimer's disease; Discontinuation; Cholinesterase inhibitor
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Dementia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Enzyme Inhibitors; Cholinesterase Inhibitors
• Other Study ID Numbers: CLIN-014-13F

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes