Trial Outcomes & Findings for Crossover Target Engagement Study of Cholinergic Mechanisms of Gait Dysfunction in Parkinson's Disease (Project #3 - Experiment 3 [UdallP3E3]) (NCT NCT04403399)

NCT ID: NCT04403399

Last Updated: 2021-01-27

Results Overview

Gait speed, how fast a person can walk down a corridor, at normal pace with no distractors (i.e., no dual task).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

34 participants

Primary outcome timeframe

end of each period: 22 and 64 days

Results posted on

2021-01-27

Participant Flow

Participant milestones

Participant milestones
Measure	Varenicline Then Placebo Patients will take varenicline initially for 3 weeks, then after a 3 week washout period, they will switch to placebo for 3 weeks.	Placebo Then Varenicline Patients will take placebo initially for 3 weeks, then after a 3 week washout period they will switch to varenicline for 3 weeks.
Period 1 STARTED	18	16
Period 1 COMPLETED	18	16
Period 1 NOT COMPLETED	0	0
Period 2 STARTED	18	16
Period 2 COMPLETED	18	15
Period 2 NOT COMPLETED	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Varenicline Then Placebo Patients will take varenicline initially for 3 weeks, then after a 3 week washout period, they will switch to placebo for 3 weeks.	Placebo Then Varenicline Patients will take placebo initially for 3 weeks, then after a 3 week washout period they will switch to varenicline for 3 weeks.
Period 2 Physician Decision	0	1

Baseline Characteristics

Crossover Target Engagement Study of Cholinergic Mechanisms of Gait Dysfunction in Parkinson's Disease (Project #3 - Experiment 3 [UdallP3E3])

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Varenicline Then Placebo n=18 Participants Patients will take varenicline initially for 3 weeks, then after a 3 week washout period, they will switch to placebo for 3 weeks.	Placebo Then Varenicline n=16 Participants Patients will take placebo initially for 3 weeks, then after a 3 week washout period, they will switch to varenicline for 3 weeks.	Total n=34 Participants Total of all reporting groups
Age, Continuous	68.1 years STANDARD_DEVIATION 5.7 • n=5 Participants	64.2 years STANDARD_DEVIATION 5.3 • n=7 Participants	66.3 years STANDARD_DEVIATION 5.78 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Sex: Female, Male Male	15 Participants n=5 Participants	13 Participants n=7 Participants	28 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	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	17 Participants n=5 Participants	16 Participants n=7 Participants	33 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	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	18 Participants n=5 Participants	16 Participants n=7 Participants	34 Participants n=5 Participants
Age at Diagnosis of Parkinson's Disease	61.3 years STANDARD_DEVIATION 6.66 • n=5 Participants	57.7 years STANDARD_DEVIATION 7.22 • n=7 Participants	59.6 years STANDARD_DEVIATION 7.06 • n=5 Participants
MDS-UPDRS III	33.2 units on a scale STANDARD_DEVIATION 13.92 • n=5 Participants	30.7 units on a scale STANDARD_DEVIATION 12.4 • n=7 Participants	32.0 units on a scale STANDARD_DEVIATION 13.07 • n=5 Participants
Geriatric Depression Scale	2.4 units on a scale STANDARD_DEVIATION 2.06 • n=5 Participants	4.3 units on a scale STANDARD_DEVIATION 4.19 • n=7 Participants	3.3 units on a scale STANDARD_DEVIATION 3.34 • n=5 Participants
Montreal Cognitive Assessment	27.2 units on a scale STANDARD_DEVIATION 2.37 • n=5 Participants	26.8 units on a scale STANDARD_DEVIATION 1.97 • n=7 Participants	27.0 units on a scale STANDARD_DEVIATION 2.17 • n=5 Participants

PRIMARY outcome

Timeframe: end of each period: 22 and 64 days

Population: All randomized participants were included in the mixed effects model. One participant randomized to the placebo then varenicline group was withdrawn by the physician early in period 2; 1 participant randomized to the varenicline then placebo group did not complete the gait assessment in period 2.

Gait speed, how fast a person can walk down a corridor, at normal pace with no distractors (i.e., no dual task).

Outcome measures

Outcome measures
Measure	Varenicline n=33 Participants 0.5 mg PO BID varenicline for 3 weeks (beginning with a 0.25 mg dose and escalated over the next 2 days)	Placebo n=33 Participants placebo given PO BID for 3 weeks
Gait Speed	121.27 cm/s Standard Error 1.36	124.89 cm/s Standard Error 1.36

PRIMARY outcome

Timeframe: end of each period: 22 and 64 days

Population: All randomized participants were included in the mixed effects model. One participant randomized to the placebo then varenicline group was withdrawn by the physician early in period 2; two participants randomized to the varenicline then placebo group did not complete the iSWAY protocol in period 2.

JERK is the time based derivative of spontaneous lower trunk accelerations during standing. It was assessed with the Ambulatory Parkinson's Disease Monitoring (APDM) wearable sensor system (APDM Wearable Technologies, Inc.) using the iSWAY protocol, with participants standing on a foam pad with eyes closed. JERK was calculated using the manufacturer's software (Mobility Lab Version 1).

Outcome measures

Outcome measures
Measure	Varenicline n=33 Participants 0.5 mg PO BID varenicline for 3 weeks (beginning with a 0.25 mg dose and escalated over the next 2 days)	Placebo n=32 Participants placebo given PO BID for 3 weeks
JERK	0.97 m^2/sec^5 Standard Error 0.20	1.04 m^2/sec^5 Standard Error 0.20

SECONDARY outcome

Timeframe: end of period: days 22 and 64

Population: All randomized participants with at least one post-treatment value were included in the mixed effects model. Six participants (1 in the placebo then varenicline, 6 in the varenicline then placebo) were unable to pass practice trials due to delayed response time (task not completed at all visits). Technical errors resulted in missing data for 2 placebo and 1 varenicline participants; 3 varenicline participants requested skipping task due to physical ailments.

Attention function will be measured with a standard computer test, the Sustained Attention Test (SAT), without a distractor condition. Results are reported as the vigilance index, a measure that corrects estimates of accurate detection with penalties for false detection and not confounded by errors of omission. (Frey PW, Colliver JA. Sensitivity and responsivity measures for discrimination learning. Learn Motiv 1973; 4:327-342.) The minimum score is -1.00 (indicating that all recorded responses were misses or false alarms) and maximum is +1 (indicating that all recorded responses were hits or correct rejections). Higher values indicate better attentional performance.

Outcome measures

Outcome measures
Measure	Varenicline n=23 Participants 0.5 mg PO BID varenicline for 3 weeks (beginning with a 0.25 mg dose and escalated over the next 2 days)	Placebo n=26 Participants placebo given PO BID for 3 weeks
Attention	0.73 units on a scale Standard Error 0.06	0.66 units on a scale Standard Error 0.06

Adverse Events

Varenicline

Serious events: 1 serious events

Other events: 17 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Varenicline n=34 participants at risk 0.5 mg PO BID varenicline for 3 weeks (beginning with a 0.25 mg dose and escalated over the next 2 days)	Placebo n=34 participants at risk placebo given PO BID for 3 weeks
Cardiac disorders Syncope, unspecified	0.00% 0/34 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)	2.9% 1/34 • Number of events 1 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)
Infections and infestations Cellulitus	2.9% 1/34 • Number of events 1 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)	0.00% 0/34 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)

Other adverse events

Additional Information

Dr. Cathie Spino, Research Professor of Biostatistics

U of Michigan

Phone: 7346155469

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Varenicline n=34 participants at risk 0.5 mg PO BID varenicline for 3 weeks (beginning with a 0.25 mg dose and escalated over the next 2 days)	Placebo n=34 participants at risk placebo given PO BID for 3 weeks
Injury, poisoning and procedural complications Fall	8.8% 3/34 • Number of events 5 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)	2.9% 1/34 • Number of events 1 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)
Nervous system disorders Lightheadedness	5.9% 2/34 • Number of events 2 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)	0.00% 0/34 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)
Gastrointestinal disorders Nausea	11.8% 4/34 • Number of events 4 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)	2.9% 1/34 • Number of events 1 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)
Gastrointestinal disorders Vomiting	5.9% 2/34 • Number of events 2 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)	2.9% 1/34 • Number of events 1 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)
Gastrointestinal disorders Constipation	2.9% 1/34 • Number of events 1 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)	0.00% 0/34 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)
Metabolism and nutrition disorders Hyperglycemia	2.9% 1/34 • Number of events 1 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)	2.9% 1/34 • Number of events 1 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)
Vascular disorders Hypertension	0.00% 0/34 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)	2.9% 1/34 • Number of events 1 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)
Infections and infestations Urinary tract infection	2.9% 1/34 • Number of events 1 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)	0.00% 0/34 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)
Nervous system disorders Headache	2.9% 1/34 • Number of events 1 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)	0.00% 0/34 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)
Musculoskeletal and connective tissue disorders Cramping in left leg	0.00% 0/34 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)	2.9% 1/34 • Number of events 1 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)
Musculoskeletal and connective tissue disorders Decreased reflexes in distal lower extremities	0.00% 0/34 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)	2.9% 1/34 • Number of events 2 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)
Psychiatric disorders Depressed mood	2.9% 1/34 • Number of events 1 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)	2.9% 1/34 • Number of events 1 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)
Musculoskeletal and connective tissue disorders Difficulty walking	0.00% 0/34 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)	2.9% 1/34 • Number of events 1 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)
Nervous system disorders Foggy/Forgetfulness	2.9% 1/34 • Number of events 1 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)	2.9% 1/34 • Number of events 1 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)
Musculoskeletal and connective tissue disorders Hammer toes	0.00% 0/34 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)	2.9% 1/34 • Number of events 1 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)
Psychiatric disorders Inability to sleep	2.9% 1/34 • Number of events 1 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)	0.00% 0/34 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)
Metabolism and nutrition disorders Increase in appetite	2.9% 1/34 • Number of events 1 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)	0.00% 0/34 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)
Nervous system disorders Increase in PD medication "off" time	8.8% 3/34 • Number of events 3 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)	0.00% 0/34 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)
Musculoskeletal and connective tissue disorders Increase stiffness in hands	0.00% 0/34 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)	2.9% 1/34 • Number of events 1 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)
Musculoskeletal and connective tissue disorders Increased tremors	0.00% 0/34 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)	2.9% 1/34 • Number of events 1 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)
Nervous system disorders Involuntary movements	2.9% 1/34 • Number of events 1 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)	0.00% 0/34 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)
Musculoskeletal and connective tissue disorders Pain in shoulder, pelvic	2.9% 1/34 • Number of events 1 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)	5.9% 2/34 • Number of events 2 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)
Nervous system disorders New onset of perception difficulty	2.9% 1/34 • Number of events 1 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)	0.00% 0/34 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)
Musculoskeletal and connective tissue disorders Tendon tear	2.9% 1/34 • Number of events 1 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)	0.00% 0/34 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)
Ear and labyrinth disorders Ringing in ears	2.9% 1/34 • Number of events 1 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)	0.00% 0/34 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)
Cardiac disorders Systolic ejection murmur	2.9% 1/34 • Number of events 1 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)	0.00% 0/34 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)
General disorders Tiredness	2.9% 1/34 • Number of events 1 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)	2.9% 1/34 • Number of events 1 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)
General disorders Toothache	2.9% 1/34 • Number of events 1 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)	0.00% 0/34 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)
Nervous system disorders Vasovagal syncope	2.9% 1/34 • Number of events 1 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)	0.00% 0/34 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)
Psychiatric disorders Vivid dreams	5.9% 2/34 • Number of events 2 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)	2.9% 1/34 • Number of events 1 • 9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)