Varenicline for Parkinson's Disease

(CRANE Trial)

Overseen By Dawn Keys

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Vikas Kotagal

Must not be taking: Dopamine blockers, Anticholinergics

Disqualifiers: Atypical Parkinsonian, Stroke, Epilepsy, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

102 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether Varenicline can help people with Parkinson's disease by reducing their risk of falling and improving their multitasking ability while walking. Participants will receive either Varenicline or a placebo (a non-active substance) and will undergo tests and complete questionnaires. Individuals diagnosed with Parkinson's disease who experience mild cognitive impairment (trouble with memory or thinking) might be suitable for this study. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that participants stop taking certain dopamine blocking drugs, specific anticholinergic drugs like trihexyphenidyl and benztropine, and specific cholinesterase inhibitors before joining. Additionally, you must not have used any nicotine products or varenicline in the last 6 months.

Is there any evidence suggesting that Varenicline is likely to be safe for humans?

Research has shown that varenicline has raised safety concerns in past studies. Reports have documented serious side effects, including 86 cases of seizures and 372 cases of movement problems such as shaking and muscle spasms. Additionally, reports have noted suicidal thoughts, aggressive behavior, and delusions. These effects are well-documented.

While varenicline can aid in quitting smoking, these side effects require careful consideration of its safety. The need for more studies suggests that its long-term safety and effects are not fully understood. Prospective trial participants should be aware of these potential risks. Consulting a healthcare provider is crucial to weigh the benefits and risks. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Parkinson's?

Varenicline is unique because it taps into a different mechanism of action compared to standard Parkinson's treatments like levodopa or dopamine agonists. While most current treatments focus on replenishing or mimicking dopamine, Varenicline targets nicotinic receptors in the brain. Researchers are excited because this approach could offer symptom relief without the common side effects associated with traditional dopamine-based therapies.

What evidence suggests that Varenicline might be an effective treatment for reducing fall risk in Parkinson's Disease?

This trial will compare Varenicline with a placebo to evaluate its effects on movement problems in Parkinson's disease. Animal research suggests that Varenicline might help with these issues by affecting certain parts of the brain. However, studies in humans have not shown that Varenicline improves balance or thinking skills in people with Parkinson's. Varenicline is already known to help people quit smoking. While early results are promising for movement issues in Parkinson's, more research is needed to confirm these effects in humans. ^{3 6 7 8 9}

Who Is on the Research Team?

Vikas Kotagal, MD

Principal Investigator

University of Michigan

Are You a Good Fit for This Trial?

This trial is for individuals with Parkinson's Disease and overactive bladder who may be at risk of falling. Participants will undergo screening to ensure they meet the study requirements before being randomly assigned to receive either Varenicline or a placebo.

Inclusion Criteria

I have mild memory or thinking problems due to Parkinson's disease.

I can give my consent or have someone who can legally do it for me.

I have been diagnosed with Parkinson's Disease.

Exclusion Criteria

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

I have used nicotine products or medications in the last 6 months.

My Parkinson's disease is advanced, with a score of 4 or higher.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Varenicline or placebo for 12 months with various tests, imaging, questionnaires, and laboratory collections

12 months

Regular visits (in-person and over the phone)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Varenicline

Trial Overview The trial is testing if Varenicline can reduce falls and improve multitasking while walking in patients with Parkinson's Disease, compared to a placebo. It involves regular visits, tests, imaging studies, questionnaires, and lab collections over one year.

How Is the Trial Designed?

Group I: Varenicline Experimental Treatment 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

Varenicline is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Chantix for:

• Smoking cessation
• Dry eye disease

Approved in European Union as Champix for:

• Smoking cessation

Approved in Canada as Champix for:

• Smoking cessation

Who Is Running the Clinical Trial?

Vikas Kotagal

Lead Sponsor

Trials

1

Recruited

100+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Published Research Related to This Trial

In a randomized controlled trial, varenicline (Chantix) demonstrated a higher abstinence rate from smoking after one year compared to both bupropion SR (Zyban) and a placebo, indicating its efficacy in treating tobacco dependence.

Despite its effectiveness, varenicline has been associated with serious neuropsychiatric side effects, highlighting the importance of discussing potential risks and benefits with patients considering this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of nicotine dependence with Chantix (varenicline). Rankin, KV., Jones, DL.[2015]

Varenicline, a medication used to help people quit smoking, is known to have some psychiatric and behavioral side effects, including reports of tardive dyskinesia, although these were not previously documented in literature.

This study presents the first two documented cases of withdrawal emergent dyskinesias associated with varenicline, highlighting a potential safety concern for users of the medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Withdrawal-Emergent Dyskinesias following Varenicline Therapy. Toffey, BA., Rabin, M., Kurlan, R.[2020]

Varenicline (Champix) is a newly approved medication for smoking cessation that acts as a partial agonist of nicotinic receptors, offering a different mechanism of action compared to traditional therapies like nicotine replacement and bupropion.

Recent studies indicate that varenicline is effective in helping individuals quit smoking and may have advantages over existing treatments, although potential side effects are also discussed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Drug of the month. Varenicline (Champix)]. Vandemergel, X.[2015]

In a study of 2,682 patients using varenicline for smoking cessation, nausea and vomiting were the most common reasons for discontinuation and the most frequently reported adverse drug reactions, highlighting the need for patient monitoring regarding gastrointestinal side effects.

While some psychiatric events were reported, including anxiety and depression, all cases of suicidal behavior involved patients with prior psychiatric conditions, suggesting that clinicians should closely monitor individuals with such histories when prescribing varenicline.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and drug utilization profile of varenicline as used in general practice in England: interim results from a prescription-event monitoring study. Kasliwal, R., Wilton, LV., Shakir, SA.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8723959/

Varenicline for the Treatment of Postural and Gait ... The results did not suggest that varenicline had an effect on balance in patients with PD. Furthermore, varenicline did not seem to affect cognition. Perhaps, ...

2. withpower.com withpower.com/trial/phase-2-parkinson-disease-1-2025-fa875

Varenicline for Parkinson's Disease (CRANE Trial) Research in rats suggests that varenicline may help improve motor deficits related to Parkinson's disease by acting on specific brain receptors. Additionally, ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02473562

Varenicline Treatment for Excessive Daytime Sleepiness in ... Sleep disturbances are common in Parkinson's disease and include excessive daytime sleepiness that has been reported in up to 50% of patients. Relatively little ...

4. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2820435

Varenicline and Nicotine Replacement Therapy for ... Varenicline is the most effective sole pharmacotherapy for smoking cessation and is as effective as combination nicotine replacement therapy ( ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34992953/

Varenicline for the Treatment of Postural and Gait ... Conclusion: The results did not suggest that varenicline had an effect on balance in patients with PD. Furthermore, varenicline did not seem to affect cognition ...

6. ismp.org ismp.org/sites/default/files/attachments/2018-01/2007Q4.pdf

Strong Safety Signal Seen for New Varenicline Risks - ISMP Serious reported events included 86 cases of convulsions (seizures), 372 reports of a wide variety of movement disorders, including tremors, muscle spasms, ...

7. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK534846/

Varenicline - StatPearls - NCBI Bookshelf - NIH Further trials are needed to determine efficacy and outcomes in patients receiving varenicline for over 12 months. Twice daily, with one spray in each nostril.

8. ismp.org ismp.org/sites/default/files/attachments/2018-01/20160912.pdf

Strengthen the Varenicline (CHANTIX) Boxed Warning ... - ISMP The cases describe suicidal behaviors, bizarre and reckless aggression, delusions, and homicidal and suicidal thoughts. The effects are documented in peer- ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3957118/

Effects of Chronic Varenicline Treatment on Nicotine, Cocaine ... Varenicline facilitates smoking cessation in clinical studies and reduced nicotine self-administration, and substituted for the nicotine-discriminative stimulus ...