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

NCT00992771 | Completed Phase 2

• 1 other identifier: 8
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 3

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.

Conditions

Spinocerebellar Ataxia Type 3

Outcome Measures

Primary Outcomes (2)

• Changes in the patient's SARA Rating Scale total score

  25 weeks

• Frequency and severity of dose-limiting adverse events

  25 weeks

Secondary Outcomes (3)

• 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

Study Arms (2)

Varneicline

EXPERIMENTAL

Drug: varenicline

Placebo

PLACEBO COMPARATOR

Drug: placebo

Interventions

varenicline DRUG

up to 1mg BID for 8 weeks

Varneicline

placebo DRUG

placebo matching varenicline, up to 1mg BID for 8 weeks

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• Age 18 years to 80 years.
• Women of child-bearing potential must use a reliable method of contraception and must provide a negative pregnancy test at entry into the study.
• 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).
• Stable doses of all medications for 30 days prior to study entry and for the duration of the study.
• Ability to ambulate with or without assistance.
• Score of 10 or higher (worse) on the SARA total score.
• Score of 3 or higher (worse) on the 'gait' subsection of the SARA rating scale.

You may not qualify if:

• 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).
• Pregnancy or lactation.
• Concurrent participation in another clinical study.
• Patients with a history of substance abuse.
• Patients who currently smoke or have smoked within the past 12 months.
• Presence of psychosis, bipolar disorder, untreated depression (BDI greater than or equal to 21), or history of suicide attempt.
• Concurrent treatment with any MAOIs, Wellbutrin, or nicotine patches.
• Dementia or other psychiatric illness that prevents the patient from giving informed consent (Mini Mental Status Exam score less than 24).
• Legal incapacity or limited legal capacity.
• Presence of severe renal disease (BUN 50% greater than normal or creatinine clearance \<60 mL/min) or hepatic disease.
• 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).
• Use of varenicline within the previous 30 days.
• 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).

Sponsors & Collaborators

• University of South Florida: lead
• National Ataxia Foundation: collaborator
• Bob Allison Ataxia Research Center (BAARC): collaborator
• Pfizer: collaborator

Study Sites (3)

University of California - Los Angeles

Los Angeles, California, 90095, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

University of South Florida

Tampa, Florida, 33612, United States

Location

MeSH Terms

Conditions

Machado-Joseph Disease

Interventions

Varenicline

Condition Hierarchy (Ancestors)

Spinocerebellar Ataxias; Cerebellar Ataxia; Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Spinocerebellar Degenerations; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Ataxia; Dyskinesias; Neurologic Manifestations; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Quinoxalines

Study Officials

• Theresa Zesiewicz, MD

  University of South Florida

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Neurology

Study Record Dates

• First Submitted: October 8, 2009
• First Posted: October 9, 2009
• Study Start: October 1, 2009
• Primary Completion: April 1, 2011
• Study Completion: April 1, 2011
• Last Updated: June 18, 2012

Record last verified: 2012-06

Locations

US (3)