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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02933372
• Date of registration: 06/04/2016
• Prospective Registration: No
• Primary sponsor: University of Michigan
• Public title: Cholinergic Mechanisms of Gait Dysfunction in Parkinson's Disease Experiments 1 & 2 - Proj #3 UdallP3
• Scientific title: Cholinergic Mechanisms of Gait Dysfunction in Parkinson's Disease Experiments 1 & 2 - Projects #3
• Date of first enrolment: October 5, 2015
• Target sample size: 25
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02933372
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Care Provider, Investigator).
• Phase: Phase 2

Contacts

• Name: Roger L Albin, MD
• Affiliation: University of Michigan

Key inclusion & exclusion 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.



Age minimum: 45 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Parkinson's Disease

Intervention(s)

Radiation: [18-Fluorine] Flubatine PET Scan

Drug: Varenicline

Other: Evaluation by Investigator

Primary Outcome(s)

Brain Varenicline Measurements with PET Scans [Time Frame: 10 days]

Secondary ID(s)

HUM00093188

Source(s) of Monetary Support

Please refer to primary and secondary sponsors