Reducing Falls With Varenicline in Hypocholinergic Parkinson Disease

NCT06679374 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: HUM002542131UG3NS133515-01A1
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 1

Brief Summary

This trial aims to test whether one year of Varenicline, when compared to placebo, can reduce fall risk and show improvement in the ability to multitask while walking. Participants that are eligible after screening for the study will be randomized to receive Varenicline or placebo. Along with the study medication participants will have visits (over the phone and in person), various tests and imaging, questionnaires, and laboratory collections.

Conditions

Parkinson Disease

Keywords

Mild Cognitive impairment; Multitasking; Reduce falls; Hypocholinergic

Outcome Measures

Primary Outcomes (1)

• Change in normal pace-dual task cost (npDTC) from baseline to 12 months.

  Normal pace-dual task cost is defined as the within-subject difference between normal pace walking speed without dual tasking to normal pace walking speed with dual tasking divided by normal pace walking speed without dual tasking, multiplied by 100.

  Baseline, 12 months

Secondary Outcomes (1)

• Number of falls from the first dose of study drug to the 12-month visit

  First dose (day 0) to 12 month visit

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Varenicline

EXPERIMENTAL

Drug: Varenicline

Interventions

Placebo DRUG

Participants will take one pill (.5 milligrams) a day for days 1-3 and then one pill (.5 milligrams) in the morning and one pill in the evening days 4-30 and months 2-12. In month 13 participants will take one pill in the morning days 1-3. Participants will be off study drug month 13 days 4-30.

Placebo

Varenicline DRUG

Participants will take one pill (.5 milligrams) a day for days 1-3 and then one pill (.5 milligrams) in the morning and one pill in the evening days 4-30 and months 2-12. In month 13 participants will take one pill in the morning days 1-3. Participants will be off study drug month 13 days 4-30.

Also known as: Chantix

Varenicline

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants with a PD diagnosis based on the Movement Disorders Society Clinical Diagnostic Criteria for Parkinson's Disease at the time of baseline screening/enrollment visit
• Participants with occipital association cortex cholinergic denervation in the lowest tertile of the normal range on F-fluoroethoxybenzovesamicol (FEOBV) Positron Emission Tomography (PET)
• Participants with legally authorized representatives (LARs) able to co-sign documented informed consent or participants that have capacity to provide informed consent upon study enrollment as ascertained by the study-specific University of California, San Diego Brief Assessment of Capacity to Consent (UBACC)
• Mild Cognitive Impairment consistent with Parkinson disease Mild Cognitive Impairment (PD-MCI)

You may not qualify if:

• Atypical Parkinsonian conditions other than Parkinson disease (PD)
• Participants initially on certain dopamine blocking drugs (per protocol), specific anticholinergic drugs (trihexyphenidyl, benztropine), or specific cholinesterase inhibitor drugs (per protocol) at the in-person screening visit
• Modified Hoehn and Yahr score of 4.0 or greater at the in-person screening visit
• Current or previous (within last 6 months of in-person screening visit) use of any product or medication containing nicotinic agents, including use of tobacco products such as cigarettes, cigars, pipes, chewing tobacco, etc., e-cigarettes, over the counter (OTC) nicotine patches, chewing gum containing nicotine, or varenicline
• Evidence of a stroke with both cortical and subcortical involvement or occipital lobe mass lesion on structural magnetic brain imaging (MRI) obtained at the in-person screening visit that would preclude co-registration and analysis of FEOBV PET data
• Participants where 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 MRI or PET imaging
• Participants limited by participation in research procedures involving ionizing radiation
• Pregnancy (test within 48 hours of the PET imaging session in women of childbearing potential) or breastfeeding at the time of in-person screening visit
• Participants with stage 4 or 5 chronic kidney disease at the time of in-person screening visit (estimated Creatinine Clearance \< 30 milliliters per minute)
• Current, significant mood disorder at the time of in-person screening/enrollment visit defined as follows: persistent (lasting longer than 2 weeks) symptoms of depression or anxiety in the 30 days preceding informed consent, as determined by self-report
• Evidence of active suicidal ideation as defined by an affirmative answer to either question 1 or 2 on the Columbia Suicide Severity Rating Scale (C-SSRS)
• History of a myocardial infarction or unstable angina in the 90 days preceding enrollment visit
• A current or previous history of epilepsy or any epileptic seizures in the 12 months preceding enrollment
• Heavy alcohol use as defined by a score of 8 or greater on the Alcohol Use Disorders Identification Test (AUDIT-self-report version) at the time of screening/enrollment visit

Sponsors & Collaborators

• Vikas Kotagal: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (1)

University of Michigan

Ann Arbor, Michigan, 48109, United States

RECRUITING

MeSH Terms

Conditions

Parkinson Disease; Cognitive Dysfunction

Interventions

Varenicline

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Vikas Kotagal, MD

  University of Michigan

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dawn Keys

CONTACT

734-615-4334; dmkeys@med.umich.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This is a double-blind study. The study personnel (except for select staff at the Data Coordinating Center (DCC) and research pharmacy).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Neurology

Study Record Dates

• First Submitted: November 5, 2024
• First Posted: November 7, 2024
• Study Start: April 9, 2025
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): January 1, 2029
• Last Updated: March 31, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Access to the dataset that is uploaded to the data repository is available to any individual that applies to them for data access. This process does not place any limitations on the use of the data for commercial purposes.

Locations

US (1)