Reducing Falls With Varenicline in Hypocholinergic Parkinson Disease (CRANE)

Vikas Kotagal

Status and phase

Enrolling

Phase 2

Conditions

Parkinson Disease

Treatments

Drug: Varenicline

Drug: Placebo

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT06679374

HUM00254213

1UG3NS133515-01A1 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full description

The hypothesis of the trial are:

The primary hypothesis is that varenicline will result in less progress in dual-task cost gait performance after 12 months of treatment compared to placebo in hypocholinergic Parkinson disease (PD) Mild Cognitive Impairment (MCI) patients.
The primary secondary hypothesis assesses whether the magnitude of effect of varenicline relative to placebo is consistent with the minimal clinically important difference (MCID) for the relative risk of falls in the 12-month double-blind treatment period.

Enrollment

102 estimated patients

Sex

All

Ages

45+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

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)

Exclusion criteria

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
Participants that are unable to swallow pills
Participants with a history of allergic reaction to varenicline
Participants that are actively taking part in another ongoing interventional (i.e., not observational) clinical trial