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

Study Description

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Spinocerebellar Ataxia Type 3	Drug: varenicline; Drug: placebo	Phase 2

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	20 participants
Allocation:	Randomized
Intervention Model:	Crossover Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	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
Study Start Date :	October 2009
Actual Primary Completion Date :	April 2011
Actual Study Completion Date :	April 2011

Arms and Interventions

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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

Outcome Measures

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Primary Outcome Measures :

1. Changes in the patient's SARA Rating Scale total score [ Time Frame: 25 weeks ]
2. Frequency and severity of dose-limiting adverse events [ Time Frame: 25 weeks ]

Secondary Outcome Measures :

1. The effect of varenicline on quality of life in patients with spinocerebellar ataxia [ Time Frame: 25 weeks ]
2. The effect of varenicline on depression and anxiety ratings [ Time Frame: 25 weeks ]
3. The effect of varenicline on the activity of daily living (ADL) in patients with spinocerebellar ataxia [ Time Frame: 25 weeks ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 80 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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).

Contacts and Locations

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Locations

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

Sponsors and Collaborators

University of South Florida

National Ataxia Foundation

Bob Allison Ataxia Research Center (BAARC)

Pfizer

Investigators

Principal Investigator:	Theresa Zesiewicz, MD	University of South Florida

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Theresa Zesiewicz, Professor of Neurology, University of South Florida
ClinicalTrials.gov Identifier:	NCT00992771 History of Changes
Other Study ID Numbers:	8
First Posted:	October 9, 2009
Last Update Posted:	June 18, 2012
Last Verified:	June 2012

Additional relevant MeSH terms:

Spinocerebellar Ataxias; Spinocerebellar Degenerations; Ataxia; Cerebellar Ataxia; Machado-Joseph Disease; Dyskinesias; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases	Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Varenicline; Nicotinic Agonists; Cholinergic Agonists; Cholinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs