NCT04403399

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

Cholinergic Mechanisms of Gait Dysfunction in Parkinson's Disease Experiment 3 - Project #3

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 34 (actual)
• Sponsor: University of Michigan · Academic / Other
• Sex: All
• Age: 45 Years
• Healthy volunteers: Not accepted

Summary

With an appropriate oral dose of Varenicline (VCN) identified from experiments 1 \& 2 of the study (see NCT02933372), the investigators will administer VCN to Parkinson Disease (PD) participants to determine if VCN improves walking speed and measures of balance. PD participants will receive VCN or a placebo (fake drug) for 3 weeks to assess the effects of VCN administration on gait speed and balance. Participants will undergo examinations to assess the intensity of their Parkinsonism and asked questions to assess their mood and thinking.

Detailed description

To demonstrate that α4β2\* nAChRs are appropriate therapeutic targets in Parkinson's Disease (PD), it is necessary to study key pharmacokinetic-pharmacodynamic features of α4β2\* nAChR in the context of the PD brain with loss of nerve cells that produce the neurotransmitter acetylcholine, a pathologic environment in which they may exhibit unique features. This personalized medicine approach focuses our studies on the subgroup of PD subjects with loss of nerve cells that produce the neurotransmitter acetylcholine identified by Project II and the Clinical Resource Core. The investigators will assess α4β2\* nAChR features using PET imaging with the α4β2\* nAChR ligand \[18-Fluorine\]flubatine, subacute administration of the α4β2\* nAChR partial agonist Varenicline (VCN), and laboratory measures of gait, balance, and attention. The investigators will use \[18-Fluorine\] flubatine PET to assess VCN occupancy of brain α4β2\* nAChRs (experiments 1 \& 2). VCN will be administered to both PD participants (experiment 1) and healthy controls (experiment 2) and both populations will undergo a flubatine PET scan to assess VCN occupancy. Using this PET data to select an appropriate VCN dose, the investigators will perform a pharmacodynamic study (experiment 3) with subacute VCN administration to determine if α4β2\* nAChR stimulation improves laboratory measures of gait function, postural control, and attentional function in PD subjects with loss of nerve cells that produce the neurotransmitter acetylcholine.

Conditions

• Parkinson's Disease

Interventions

Type	Name	Description
DRUG	Varenicline	Initial 0.25 mg oral dose of varenicline administered with monitoring over 4 hours, then total daily dose escalated over the next 2 days until final 0.5 mg BID oral varenicline administered for the remaining 3 weeks.
DRUG	Placebo	Initial placebo oral dose administered with monitoring over 4 hours, then total daily dose escalated over the next 2 days until final placebo BID dosing administered orally for the remaining 3 weeks.

Timeline

• Start date: 2017-06-29
• Primary completion: 2019-06-26
• Completion: 2019-06-26
• First posted: 2020-05-27
• Last updated: 2021-01-27
• Results posted: 2021-01-27

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study