Study to Determine the Safety and Tolerability of Varenicline (Chantix®) in Treating Spinocerebellar Ataxia Type 3

A Pilot, Randomized, Double-blind, Placebo-controlled Phase I Study to Determine the Safety and Tolerability of Varenicline (Chantix®) in Treating Spinocerebellar Ataxia Type 3

Spinocerebellar ataxia (SCA) is a group of inherited disorders characterized by cerebellar degeneration leading to imbalance, incoordination, speech difficulties and problems with walking. Recently, individual case reports have suggested that varenicline, a drug used in smoking cessation, produces substantial improvement in patients with several inherited ataxias. A modest response was noted in 5 patients with SCA, suggesting that it is potentially efficacious in this disorder as well. Although this agent is available for off-label use, the severe side effects noted with its use and the lack of long-term toxicity data demand that it be systematically assessed. The present study will test whether varenicline is safe and potentially efficacious in a heterogeneous cohort of adults with SCA.

Study Overview

• Status: Completed
• Conditions: Spinocerebellar Ataxia Type 3
• Intervention / Treatment: Drug: varenicline; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • University of California - Los Angeles
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
    • Tampa, Florida, United States, 33612
      • University of South Florida

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Outpatients with spinocerebellar ataxia type 3 diagnosed by a movement disorder specialist and confirmed by genetic testing (of the patient or in a first degree relative of the patient).
2. Age 18 years to 80 years.
3. Women of child-bearing potential must use a reliable method of contraception and must provide a negative pregnancy test at entry into the study.
4. Serum creatine kinase, complete metabolic panel, complete blood count, liver function tests, renal function tests, platelets and EKG are within normal limits (results obtained from primary care physician and dated within the past 6 months or obtained at screening visit).
5. Stable doses of all medications for 30 days prior to study entry and for the duration of the study.
6. Ability to ambulate with or without assistance.
7. Score of 10 or higher (worse) on the SARA total score.
8. Score of 3 or higher (worse) on the 'gait' subsection of the SARA rating scale.

Exclusion Criteria:

1. Any unstable illness or concomitant medical condition that, in the investigator's opinion, precludes participation in this study. This includes other disorders that may affect gait or balance (stroke, arthritis, etc).
2. Pregnancy or lactation.
3. Concurrent participation in another clinical study.
4. Patients with a history of substance abuse.
5. Patients who currently smoke or have smoked within the past 12 months.
6. Presence of psychosis, bipolar disorder, untreated depression (BDI greater than or equal to 21), or history of suicide attempt.
7. Concurrent treatment with any MAOIs, Wellbutrin, or nicotine patches.
8. Dementia or other psychiatric illness that prevents the patient from giving informed consent (Mini Mental Status Exam score less than 24).
9. Legal incapacity or limited legal capacity.
10. Presence of severe renal disease (BUN 50% greater than normal or creatinine clearance <60 mL/min) or hepatic disease.
11. Abnormal creatine kinase and/or platelet count in the past 6 months (as determined by lab reports obtained from primary care physicians or conducted at baseline).
12. Use of varenicline within the previous 30 days.
13. Ataxia derived from any other cause than genetically-confirmed SCA (including but not limited to alcoholism, head injury, Multiple Sclerosis, olivo-ponto-cerebellar atrophy or multiple system atrophy).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: placebo; placebo matching varenicline, up to 1mg BID for 8 weeks
Experimental: Varneicline	Drug: varenicline; up to 1mg BID for 8 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Changes in the patient's SARA Rating Scale total score	25 weeks
Frequency and severity of dose-limiting adverse events	25 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
The effect of varenicline on quality of life in patients with spinocerebellar ataxia	25 weeks
The effect of varenicline on depression and anxiety ratings	25 weeks
The effect of varenicline on the activity of daily living (ADL) in patients with spinocerebellar ataxia	25 weeks

Collaborators and Investigators

• Sponsor: University of South Florida
• Collaborators: Pfizer; National Ataxia Foundation; Bob Allison Ataxia Research Center (BAARC)

Study record dates

Study Major Dates

• Study Start: October 1, 2009
• Primary Completion (Actual): April 1, 2011
• Study Completion (Actual): April 1, 2011

Study Registration Dates

• First Submitted: October 8, 2009
• First Submitted That Met QC Criteria: October 8, 2009
• First Posted (Estimate): October 9, 2009

Study Record Updates

• Last Update Posted (Estimate): June 18, 2012
• Last Update Submitted That Met QC Criteria: June 15, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Genetic Diseases, Inborn; Neurodegenerative Diseases; Dyskinesias; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Cerebellar Diseases; Ataxia; Cerebellar Ataxia; Spinocerebellar Ataxias; Spinocerebellar Degenerations; Machado-Joseph Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Nicotinic Agonists; Cholinergic Agonists; Varenicline
• Other Study ID Numbers: 8

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No