Parkinson DiseasePhase 2CRANENCT06679374
Reducing Falls With Varenicline in Hypocholinergic Parkinson Disease
A Phase 2 study testing Varenicline in people with Parkinson Disease, run by Vikas Kotagal at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 45 years and older
- Conditions the study is for
- Parkinson Disease
- What is being tested?
- Varenicline
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 102 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Apr 2025to Jan 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Michigan
Ann Arbor, Michigan, 48109
Dawn Keys, 734-615-4334, dmkeys@med.umich.edu
Vikas Kotagal, MD
About this study
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.
Read the detailed 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.
- Conditions
- Parkinson Disease
- Being tested
- Placebo, Varenicline
- Keywords
- Mild Cognitive impairment, Multitasking, Reduce falls, Hypocholinergic
- Medical subject headings
- Parkinson Disease, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
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.
VareniclineDrug
Also called Chantix
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.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
| Varenicline | Experimental | Not described Receives: Drug: Varenicline |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline, 12 months
Secondary outcomes (1)
Number of falls from the first dose of study drug to the 12-month visit
Participants will complete a fall diary to collect this data.
Measured: First dose (day 0) to 12 month visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2024
- Study start9 Apr 2025
- Primary completionJan 2029 (estimated)
- Study completionJan 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Parkinson DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 102 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Vikas Kotagal
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Vikas Kotagal, University of Michigan
- Investigators
- Vikas Kotagal, MD, Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06679374
- Sponsor's protocol ID
- HUM00254213
- Other IDs
- 1UG3NS133515-01A1
- Acronym
- CRANE
- Status last verified
- Mar 2026
- First submitted
- 5 Nov 2024
- Last updated
- 31 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The study team will ensure the dataset is shared by the occurrence of the earlier of the following two milestones: either the date of primary publication or within 9 months of lifting of the data lock. De-identified subject data will be uploaded in a timely manner to a data repository using an established data transfer mechanism and the NINDS supported Common Data Elements (CDEs) as appropriate. Pending appropriate permissions, biospecimens (DNA) will be banked in the NINDS biorepository. Uploaded datasets will be coded and stripped of identifiers in order to prevent the possibility of identifying participants in this study from the publicly available dataset.
Study at a glance
From the registry record, last updated by the sponsor on 31 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Reducing Falls With Varenicline in Hypocholinergic Parkinson Disease
- ClinicalTrials.gov ID
- NCT06679374
- Acronym / sponsor ID
- CRANE / HUM00254213
- Conditions
- Parkinson Disease
- Keywords
- Mild Cognitive impairment, Multitasking, Reduce falls, Hypocholinergic
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 102 participants (estimated)
- Lead sponsor
- Vikas KotagalUniversity, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- 9 Apr 2025 (actual)
- Primary completion
- Jan 2029 (estimated)
- Study completion
- Jan 2029 (estimated)
- First posted
- 7 Nov 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placebo |
| Varenicline | Experimental | Drug: Varenicline |
Who may qualify
- Ages
- 45 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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)
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboParticipants 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 | Placebo |
| VareniclineAlso: ChantixParticipants 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 |
Primary outcome
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.
1 secondary outcome
Number of falls from the first dose of study drug to the 12-month visit
Time frame: First dose (day 0) to 12 month visit
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Mar 2026.
- Individual participant dataSharing planned: Yes. The study team will ensure the dataset is shared by the occurrence of the earlier of the following two milestones: either the date of primary publication or within 9 months of lifting of the data lock. De-identified subject data will be uploaded in a timely manner to a data repository using an established data transfer mechanism and the NINDS supported Common Data Elements (CDEs) as appropriate. Pending appropriate permissions, biospecimens (DNA) will be banked in the NINDS biorepository. Uploaded datasets will be coded and stripped of identifiers in order to prevent the possibility of identifying participants in this study from the publicly available dataset.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Vikas Kotagal, MD principal investigator
University of Michigan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Varenicline in people with Parkinson Disease, run by Vikas Kotagal at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 31 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Dawn Keys (734-615-4334, dmkeys@med.umich.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in normal pace-dual task cost (npDTC) from baseline to 12 months. (time frame: Baseline, 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Mar 2026.