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

NCT04403399 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: HUM00093188-a
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Parkinson's Disease

Outcome Measures

Primary Outcomes (2)

• Gait Speed

  Gait speed, how fast a person can walk down a corridor, at normal pace with no distractors (i.e., no dual task).

  end of each period: 22 and 64 days

• JERK

  JERK is the time based derivative of spontaneous lower trunk accelerations during standing. It was assessed with the Ambulatory Parkinson's Disease Monitoring (APDM) wearable sensor system (APDM Wearable Technologies, Inc.) using the iSWAY protocol, with participants standing on a foam pad with eyes closed. JERK was calculated using the manufacturer's software (Mobility Lab Version 1).

  end of each period: 22 and 64 days

Secondary Outcomes (1)

• Attention

  end of period: days 22 and 64

Study Arms (2)

Varenicline then Placebo

EXPERIMENTAL

Varenicline 0.5 mg BID orally for 3 weeks, followed by a 3-week washout period, then placebo BID orally for 3 weeks

Drug: Varenicline; Drug: Placebo

Placebo then Varenicline

EXPERIMENTAL

Placebo BID orally for 3 weeks, followed by a 3-week washout period, then Varenicline 0.5 mg BID orally for 3 weeks

Drug: Varenicline; Drug: Placebo

Interventions

Varenicline DRUG

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.

Also known as: Chantix

Placebo then Varenicline; Varenicline then Placebo

Placebo DRUG

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.

Placebo then Varenicline; Varenicline then Placebo

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: No
• 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

Study Sites (1)

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Related Publications (1)

• Mancini M, Carlson-Kuhta P, Zampieri C, Nutt JG, Chiari L, Horak FB. Postural sway as a marker of progression in Parkinson's disease: a pilot longitudinal study. Gait Posture. 2012 Jul;36(3):471-6. doi: 10.1016/j.gaitpost.2012.04.010. Epub 2012 Jun 29.

  PMID: 22750016 RESULT

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: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Neurology

Study Record Dates

• First Submitted: May 21, 2020
• First Posted: May 27, 2020
• Study Start: June 29, 2017
• Primary Completion: June 26, 2019
• Study Completion: June 26, 2019
• Last Updated: January 27, 2021
• Results First Posted: January 27, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)