Clinical trial NCT00992771: Study to Determine the Safety and Tolerability of Varenicline (Chantix®) in Treating Spinocerebellar Ataxia Type 3
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Spinocerebellar Ataxia Type 3
Lead sponsor: University of South Florida
Sponsor class: OTHER
Collaborators: name: National Ataxia Foundation
name: Bob Allison Ataxia Research Center (BAARC)
name: Pfizer
First posted: 2009-10-09
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility 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).

Primary outcomes:
measure: Changes in the patient's SARA Rating Scale total score
timeFrame: 25 weeks
measure: Frequency and severity of dose-limiting adverse events
timeFrame: 25 weeks
Secondary outcomes:
measure: The effect of varenicline on quality of life in patients with spinocerebellar ataxia
timeFrame: 25 weeks
measure: The effect of varenicline on depression and anxiety ratings
timeFrame: 25 weeks
measure: The effect of varenicline on the activity of daily living (ADL) in patients with spinocerebellar ataxia
timeFrame: 25 weeks
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California - Los Angeles
state: California
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
Study officials:
affiliation: University of South Florida
name: Theresa Zesiewicz, MD
role: PRINCIPAL_INVESTIGATOR
References: