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 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.

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.

How does the drug varenicline differ from other treatments for Parkinson's disease?

Varenicline is unique because it acts as a partial agonist at specific nicotinic acetylcholine receptors, which may help improve motor deficits in Parkinson's disease, unlike traditional treatments that primarily focus on dopamine replacement. ^{1 2 3 4 5}

What evidence supports the effectiveness of the drug varenicline for Parkinson's disease?

Research in rats suggests that varenicline may help improve motor deficits related to Parkinson's disease by acting on specific brain receptors. Additionally, varenicline has shown benefits in improving balance and coordination in conditions similar to Parkinson's, indicating potential usefulness for this disease. ^{1 2 3 4 6}

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 been diagnosed with Parkinson's Disease.

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

My brain scan shows low cholinergic activity in a specific part.

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 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]

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]

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 (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]

Citations

1. New Zealand 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. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Neuronal nicotinic receptor agonists improve gait and balance in olivocerebellar ataxia. [2021]

3. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Withdrawal-Emergent Dyskinesias following Varenicline Therapy. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Treatment of nicotine dependence with Chantix (varenicline). [2015]

5. England pubmed.ncbi.nlm.nih.gov

Effect of varenicline on behavioral deficits in a rat model of Parkinson's disease induced by unilateral 6-hydroxydopamine lesion of substantia nigra. [2019]

6. Belgium pubmed.ncbi.nlm.nih.gov

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