Overview

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

Status:
Completed
Trial end date:
2019-06-26
Target enrollment:
0
Participant gender:
All
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).
Phase:
Phase 2
Accepts Healthy Volunteers?
Accepts Healthy Volunteers
Details
Lead Sponsor:
University of Michigan
Treatments:
Cholinergic Agents
Varenicline
Criteria
Inclusion Criteria:

1. 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.

2. Stable dopaminergic replacement therapy for 3 months prior to enrollment and expected
to maintain stable dopaminergic therapy for duration of study participation.

Exclusion Criteria:

1. Other disorders which may resemble PD with or without dementia, such as vascular
dementia, normal pressure hydrocephalus, progressive supranuclear palsy, multiple
system atrophy, corticobasal ganglionic degeneration, or toxic causes of parkinsonism.
Prototypical cases have distinctive clinical profiles, like vertical supranuclear gaze
palsy, early and severe dysautonomia or appendicular apraxia, which may differentiate
them from idiopathic PD. The use of the UKPDSBRC clinical diagnostic criteria for PD
will mitigate the inclusion of subjects with atypical parkinsonism and all
participants will undergo [11-Carbon]dihydrotetrabenazine PET to confirm striatal
dopaminergic denervation.

2. Subjects on neuroleptic, anticholinergic (trihexphenidyl, benztropine), or
cholinesterase inhibitor drugs.

3. 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.

4. Evidence of a stroke or mass lesion on structural brain imaging (MRI).

5. 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.

6. Severe claustrophobia precluding MR or PET imaging

7. Subjects limited by participation in research procedures involving ionizing radiation.

8. Pregnancy (test within 48 hours of each PET session) or breastfeeding.

9. Significant risk of cardiovascular event.

10. Active, significant mood disorder.