Trial Outcomes & Findings for Cholinesterase Inhibitor Discontinuation (NCT NCT02248636)

Last Updated: 2020-10-23

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

72 participants

Primary outcome timeframe

6 weeks

Results posted on

2020-10-23

Participant Flow

Veterans who have received a prescription for a cholinesterase inhibitor for one year or greater.

72 people were enrolled and consented, but only 61 were randomized.

Participant milestones

Participant milestones
Measure	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.	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
Overall Study STARTED	26	35
Overall Study COMPLETED	20	32
Overall Study NOT COMPLETED	6	3

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Cholinesterase Inhibitor Discontinuation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Real Discontinuation n=26 Participants 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.	Sham Discontinuation n=35 Participants 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.	Total n=61 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Age, Categorical >=65 years	23 Participants n=5 Participants	33 Participants n=7 Participants	56 Participants n=5 Participants
Age, Continuous	77.34 years STANDARD_DEVIATION 10.48 • n=5 Participants	77.94 years STANDARD_DEVIATION 9.72 • n=7 Participants	77.69 years STANDARD_DEVIATION 9.97 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Sex: Female, Male Male	25 Participants n=5 Participants	35 Participants n=7 Participants	60 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	26 Participants n=5 Participants	34 Participants n=7 Participants	60 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	25 Participants n=5 Participants	29 Participants n=7 Participants	54 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: 6 weeks

Outcome measures

Outcome measures
Measure	Real Discontinuation n=26 Participants 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.	Sham Discontinuation n=35 Participants 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
Successful Completion	20 Participants	32 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Real Discontinuation n=12 Participants 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.	Sham Discontinuation n=18 Participants 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
Caregiver Burden	5.58 Change in Zarit score Standard Deviation 11.13	1.66 Change in Zarit score Standard Deviation 17.56

SECONDARY outcome

Timeframe: 6 weeks

Population: Some of the participants refused to complete the cognitive instrument over the phone.

Six-Item Screener is a telephone-based assessment of cognitive status. The score ranges from 0 to 6. A higher score indicates better cognition.

Outcome measures

Outcome measures
Measure	Real Discontinuation n=20 Participants 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.	Sham Discontinuation n=30 Participants 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
Veteran Cognition	-0.15 Change in Six-Item Screener Score Standard Deviation 2.13	0.13 Change in Six-Item Screener Score Standard Deviation 0.90

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Real Discontinuation n=26 Participants 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.	Sham Discontinuation n=35 Participants 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
Veteran Functioning	-1.44 score on a scale Standard Deviation 11.87	-0.59 score on a scale Standard Deviation 6.72

SECONDARY outcome

Timeframe: 6 weeks

Population: Not all caregivers were willing to respond to all the items.

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.

Outcome measures

Outcome measures
Measure	Real Discontinuation n=24 Participants 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.	Sham Discontinuation n=35 Participants 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
Behavioral Symptoms	-1.63 score on a scale Standard Deviation 6.26	-1.23 score on a scale Standard Deviation 3.79

SECONDARY outcome

Timeframe: 12 weeks

Population: We were unable to reach some participants at 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.

Outcome measures

Outcome measures
Measure	Real Discontinuation n=25 Participants 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.	Sham Discontinuation n=32 Participants 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
Post-study Treatment Choice Participants taking pre-study medication	13 Participants	25 Participants
Post-study Treatment Choice Participants not taking pre-study medication	12 Participants	7 Participants

Adverse Events

Real Discontinuation

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Sham Discontinuation

Serious events: 0 serious events

Other events: 3 other events

Deaths: 1 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Real Discontinuation n=26 participants at risk 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.	Sham Discontinuation n=35 participants at risk 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
Psychiatric disorders Behavior	34.6% 9/26 • Number of events 9 • 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.	8.6% 3/35 • Number of events 3 • 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.

Additional Information

William Banks, Associate Chief of Staff for Research

Puget Sound VA

Phone: 206 764-2701

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place