Trial Outcomes & Findings for Cholinergic Mechanisms of Gait Dysfunction in Parkinson's Disease Experiments 1 & 2 - Proj #3 (NCT NCT02933372)
NCT ID: NCT02933372
Last Updated: 2021-02-12
Results Overview
Varenicline occupancy of alpha4beta2\* nicotinic acetylcholine receptors (nAChR) was assessed with ascending doses of varenicline and the selective alpha4beta2\* nAChR positron emission tomography (PET) ligand \[18F\]Flubatine. Alpha4beta2\* nAChR agonists may induce nAChR expression. Consequently, we imaged participants at the end of their drug exposure periods (Day 10) and again after 5 days (\~5 half-lives) of washout from drug exposure (Day 15). We used the difference between the two PET scans, (Day 10 - Day 15)/Day 15 x 100%, to determine the receptor occupancy of alpha4beta2\* nicotinic acetylcholine receptors (nAChR) by each dose of varenicline.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
25 participants
Primary outcome timeframe
15 days
Results posted on
2021-02-12
Participant Flow
Participant milestones
| Measure |
Parkinson's Disease Patients
Participants take varenicline for 10 days. Each participant will be on one dosage throughout the 10 days, but not all participants receive the same dosage. The dosages that were utilized were 0.25mg once a day, 0.25mg twice a day, 0.5mg twice a day and 1mg twice a day.
|
Healthy Controls
Participants take varenicline for 10 days. Each participant will be on one dosage throughout the 10 days, but not all participants receive the same dosage. The dosages that were utilized were 0.25mg once a day, 0.25mg twice a day, and 0.5mg twice a day.
|
|---|---|---|
|
Overall Study
STARTED
|
15
|
10
|
|
Overall Study
COMPLETED
|
15
|
10
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Cholinergic Mechanisms of Gait Dysfunction in Parkinson's Disease Experiments 1 & 2 - Proj #3
Baseline characteristics by cohort
| Measure |
Parkinson's Disease Patients
n=15 Participants
Participants take varenicline for 10 days. Each participant will be on one dosage throughout the 10 days, but not all participants receive the same dosage. The dosages that were utilized were 0.25mg once a day, 0.25mg twice a day, 0.5mg twice a day and 1mg twice a day.
|
Healthy Controls
n=10 Participants
: Participants take varenicline for 10 days. Each participant will be on one dosage throughout the 10 days, but not all participants receive the same dosage. The dosages that were utilized were 0.25mg once a day, 0.25mg twice a day, and 0.5mg twice a day.
|
Total
n=25 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
67.3 years
STANDARD_DEVIATION 5.20 • n=5 Participants
|
66.4 years
STANDARD_DEVIATION 8.95 • n=7 Participants
|
66.9 years
STANDARD_DEVIATION 6.78 • n=5 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
22 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
|
15 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
25 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 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
|
14 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
24 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
|
15 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
25 Participants
n=5 Participants
|
|
MDS-UPDRS III
|
31.9 units on a scale
STANDARD_DEVIATION 12.83 • n=5 Participants
|
3.5 units on a scale
STANDARD_DEVIATION 1.84 • n=7 Participants
|
20.5 units on a scale
STANDARD_DEVIATION 17.27 • n=5 Participants
|
|
Geriatric Depression Scale
|
3.2 units on a scale
STANDARD_DEVIATION 3.75 • n=5 Participants
|
1.6 units on a scale
STANDARD_DEVIATION 2.01 • n=7 Participants
|
2.6 units on a scale
STANDARD_DEVIATION 3.22 • n=5 Participants
|
|
Montreal Cognitive Assessment
|
25.5 units on a scale
STANDARD_DEVIATION 1.73 • n=5 Participants
|
26.8 units on a scale
STANDARD_DEVIATION 2.30 • n=7 Participants
|
26.0 units on a scale
STANDARD_DEVIATION 2.04 • n=5 Participants
|
PRIMARY outcome
Timeframe: 15 daysPopulation: All consented and treated participants who had adequate PET scans. In Parkinson's Disease cohort, there were technical difficulties with PET scans in 5 participants. In the Healthy Controls cohort, one participant's data was excluded because of suspected covert tobacco abuse and there were technical difficulties with the PET scan for one participant.
Varenicline occupancy of alpha4beta2\* nicotinic acetylcholine receptors (nAChR) was assessed with ascending doses of varenicline and the selective alpha4beta2\* nAChR positron emission tomography (PET) ligand \[18F\]Flubatine. Alpha4beta2\* nAChR agonists may induce nAChR expression. Consequently, we imaged participants at the end of their drug exposure periods (Day 10) and again after 5 days (\~5 half-lives) of washout from drug exposure (Day 15). We used the difference between the two PET scans, (Day 10 - Day 15)/Day 15 x 100%, to determine the receptor occupancy of alpha4beta2\* nicotinic acetylcholine receptors (nAChR) by each dose of varenicline.
Outcome measures
| Measure |
Parkinson's Disease Patients
n=10 Participants
Participants take varenicline for several days and have two Positron Emission Tomography (PET) scans. PET scans are used to estimate how much varenicline is actually in the brain. Safety monitoring with clinical assessments of severity of Parkinson disease (PD) and cognition are performed.
Varenicline: Participants take varenicline for 10 days. Each participant will be on one dosage throughout the 10 days, but not all participants receive the same dosage. The dosages that were utilized were 0.25mg once a day, 0.25mg twice a day, 0.5mg twice a day and 1mg twice a day.
\[18-Fluorine\] Flubatine PET Scan: Participants will undergo 2 different PET scanning sessions. Radiotracers will be injected into the participant's vein through an IV (intravenous catheter or plastic "tube" inserted in an arm vein). A tracer refers to a small amount of a radioactive substance that does not alter body function.
Evaluation by Investigator: Participants will undergo cognitive testing, a physical exam, and gait and posture assessments
|
Healthy Controls
n=9 Participants
Participants take varenicline for several days and have two Positron Emission Tomography (PET) scans. The PET scans are used to estimate how much varenicline is actually in the brain. Safety monitoring with clinical assessments for presence of Parkinson disease (PD) and cognition are performed.
Varenicline: Participants take varenicline for 10 days. Each participant will be on one dosage throughout the 10 days, but not all participants receive the same dosage. The dosages that were utilized were 0.25mg once a day, 0.25mg twice a day, 0.5mg twice a day and 1mg twice a day.
\[18-Fluorine\] Flubatine PET Scan: Participants will undergo 2 different PET scanning sessions. Radiotracers will be injected into the participant's vein through an IV (intravenous catheter or plastic "tube" inserted in an arm vein). A tracer refers to a small amount of a radioactive substance that does not alter body function.
Evaluation by Investigator: Participants will undergo cognitive testing, a physical exam, and gait and posture assessments
|
|---|---|---|
|
Varenicline Occupancy of alpha4beta2* Nicotinic Acetylcholine Receptors
0.25 mg once daily Varenicline
|
67.0 percentage of VCN-alpha4beta2* nAChRs
Standard Deviation 4.9
|
67.9 percentage of VCN-alpha4beta2* nAChRs
Standard Deviation 3.1
|
|
Varenicline Occupancy of alpha4beta2* Nicotinic Acetylcholine Receptors
0.25 mg twice daily Varenicline
|
65.7 percentage of VCN-alpha4beta2* nAChRs
Standard Deviation 8.0
|
70.6 percentage of VCN-alpha4beta2* nAChRs
Standard Deviation 1.9
|
|
Varenicline Occupancy of alpha4beta2* Nicotinic Acetylcholine Receptors
0.5 mg twice daily Varenicline
|
66.3 percentage of VCN-alpha4beta2* nAChRs
Standard Deviation 5.0
|
69.6 percentage of VCN-alpha4beta2* nAChRs
Standard Deviation 4.0
|
|
Varenicline Occupancy of alpha4beta2* Nicotinic Acetylcholine Receptors
1 mg twice daily Varenicline
|
71.5 percentage of VCN-alpha4beta2* nAChRs
Standard Deviation 10.6
|
—
|
Adverse Events
Parkinson's Disease Patients
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Healthy Controls
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Parkinson's Disease Patients
n=15 participants at risk
Participants take varenicline for 10 days. Each participant will be on one dosage throughout the 10 days, but not all participants receive the same dosage. The dosages that were utilized were 0.25mg once a day, 0.25mg twice a day, 0.5mg twice a day and 1mg twice a day.
|
Healthy Controls
n=10 participants at risk
Participants take varenicline for 10 days. Each participant will be on one dosage throughout the 10 days, but not all participants receive the same dosage. The dosages that were utilized were 0.25mg once a day, 0.25mg twice a day, and 0.5mg twice a day.
|
|---|---|---|
|
Gastrointestinal disorders
Nausea
|
13.3%
2/15 • Number of events 2 • 15 days
|
0.00%
0/10 • 15 days
|
|
Injury, poisoning and procedural complications
Fall
|
6.7%
1/15 • Number of events 1 • 15 days
|
0.00%
0/10 • 15 days
|
|
Musculoskeletal and connective tissue disorders
Stomach cramping
|
6.7%
1/15 • Number of events 1 • 15 days
|
0.00%
0/10 • 15 days
|
|
Nervous system disorders
Lightheadedness
|
13.3%
2/15 • Number of events 2 • 15 days
|
0.00%
0/10 • 15 days
|
|
Gastrointestinal disorders
Vomiting
|
6.7%
1/15 • Number of events 1 • 15 days
|
0.00%
0/10 • 15 days
|
|
Renal and urinary disorders
Blood in urine
|
6.7%
1/15 • Number of events 1 • 15 days
|
0.00%
0/10 • 15 days
|
|
General disorders
Tiredness
|
6.7%
1/15 • Number of events 1 • 15 days
|
0.00%
0/10 • 15 days
|
|
Psychiatric disorders
ended PET scan prior to completion
|
6.7%
1/15 • Number of events 1 • 15 days
|
0.00%
0/10 • 15 days
|
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