Cholinergic Mechanisms of Gait Dysfunction in Parkinson's Disease Experiments 1 & 2 - Proj #3

NCT02933372 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: HUM00093188
• Study Type: interventional
• Target: 25
• Locations: 0 countries
• Sites: N/A

Brief Summary

Varying oral doses of Varenicline (VCN), starting with very low doses, will be administered to participants with Parkinson's Disease (PD) or healthy controls without PD for several days. Positron emission tomography (PET) scans after administration of VCN will be used to determine the lowest oral dose of VCN producing an adequate brain level of VCN. These experiments (1 \& 2) will be used to determine an appropriate oral dose of VCN to administer to PD participants for experiment 3 of the study (see NCT04403399).

Conditions

Parkinson's Disease

Outcome Measures

Primary Outcomes (1)

• Varenicline Occupancy of alpha4beta2* Nicotinic Acetylcholine Receptors

  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.

  15 days

Study Arms (2)

Parkinson's Disease Patients

EXPERIMENTAL

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.

Drug: Varenicline

Healthy Controls

EXPERIMENTAL

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.

Drug: Varenicline

Interventions

Varenicline DRUG

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 for both Parkinson's disease participants and healthy volunteers were 0.25mg once a day, 0.25mg twice a day, and 0.5mg twice a day. A fourth dosing group of 1 mg varenicline twice a day was studied in Parkinson's disease participants, but not in healthy volunteers.

Also known as: Chantix

Healthy Controls; Parkinson's Disease Patients

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• PD diagnosis will be based on the United Kingdom Parkinson's Disease Society Brain Bank Research Center (UKPDSBRC) clinical diagnostic criteria. The investigators will enrich the cohort by recruiting subjects at modified Hoehn and Yahr stages 2 or higher, duration of motor disease 5 years or longer, age \>65 years, or the Postural Instability and Gait Disorder (PIGD) phenotype. Duration of motor disease will be defined as the time between onset of motor symptoms and time of entry into the study. The PIGD phenotype is defined as described previously. PD subjects with defined cholinergic deficits will be recruited as described in Project II. PD subjects will have cortical cholinergic deficits based on 5th percentile cutoff of the normal controls as defined previously.
• Stable dopaminergic replacement therapy for 3 months prior to enrollment and expected to maintain stable dopaminergic therapy for duration of study participation.

You may not qualify if:

• Subjects on neuroleptic, anticholinergic (trihexphenidyl, benztropine), or cholinesterase inhibitor drugs.
• Current or previous (within last 6 months) use of any product or medication containing nicotinic agents,including use of tobacco products such as cigarettes, cigars, pipes, chewing tobacco, etc., electronic cigarettes, over-the-counter nicotine patches, chewing gum containing nicotine, or varenicline.
• Evidence of a stroke or mass lesion on structural brain imaging (MRI).
• Participants in whom magnetic resonance imaging (MRI) is contraindicated including, but not limited to, those with a pacemaker, presence of metallic fragments near the eyes or spinal cord, or cochlear implant.
• Severe claustrophobia precluding MR or PET imaging
• Subjects limited by participation in research procedures involving ionizing radiation.
• Pregnancy (test within 48 hours of each PET session) or breastfeeding.
• Significant risk of cardiovascular event.
• Active, significant mood disorder.

Sponsors & Collaborators

• University of Michigan: lead

MeSH Terms

Conditions

Parkinson Disease

Interventions

Varenicline

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Quinoxalines

Results Point of Contact

• Title: Dr. Cathie Spino, Research Professor of Biostatistics
• Organization: U of Michigan

spino@umich.edu

7346155469

Study Officials

• Roger L Albin, MD

  University of Michigan

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Neurology

Model Details: All participants (Parkinson's disease patients and healthy controls) will receive the study drug varenicline.

Study Record Dates

• First Submitted: April 6, 2016
• First Posted: October 14, 2016
• Study Start: October 5, 2015
• Primary Completion: June 26, 2019
• Study Completion: June 26, 2019
• Last Updated: February 12, 2021
• Results First Posted: February 12, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share