NCT06679374 · Vikas Kotagal
Reducing Falls With Varenicline in Hypocholinergic Parkinson Disease
(CRANE)
What this study is 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 randomly assigned to receive Varenicline or placebo.
View original scientific description
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.
Interventions
DRUG
Placebo
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.
DRUG
Varenicline
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.
Primary outcome measures
Change in normal pace-dual task cost (npDTC) from baseline to 12 months.
Time frame: Baseline, 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.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
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
Where
- Ann Arbor, Michigan
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Mar 31, 2026 · Source of record for eligibility and locations