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

This study has been completed.
Sponsor:
Collaborators:
National Ataxia Foundation
Bob Allison Ataxia Research Center (BAARC)
Pfizer
Information provided by (Responsible Party):
Theresa Zesiewicz, University of South Florida
ClinicalTrials.gov Identifier:
NCT00992771
First received: October 8, 2009
Last updated: June 15, 2012
Last verified: June 2012
  Purpose

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 Intervention Phase
Spinocerebellar Ataxia Type 3
Drug: varenicline
Drug: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by University of South Florida:

Primary Outcome Measures:
  • Changes in the patient's SARA Rating Scale total score [ Time Frame: 25 weeks ] [ Designated as safety issue: No ]
  • Frequency and severity of dose-limiting adverse events [ Time Frame: 25 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • The effect of varenicline on quality of life in patients with spinocerebellar ataxia [ Time Frame: 25 weeks ] [ Designated as safety issue: No ]
  • The effect of varenicline on depression and anxiety ratings [ Time Frame: 25 weeks ] [ Designated as safety issue: No ]
  • The effect of varenicline on the activity of daily living (ADL) in patients with spinocerebellar ataxia [ Time Frame: 25 weeks ] [ Designated as safety issue: No ]

Enrollment: 20
Study Start Date: October 2009
Study Completion Date: April 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00992771

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

No publications provided

Responsible Party: Theresa Zesiewicz, Professor of Neurology, University of South Florida
ClinicalTrials.gov Identifier: NCT00992771     History of Changes
Other Study ID Numbers: 8
Study First Received: October 8, 2009
Last Updated: June 15, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Spinocerebellar Ataxias
Spinocerebellar Degenerations
Machado-Joseph Disease
Ataxia
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Cerebellar Ataxia
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
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 16, 2014