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Safety and Efficacy of Lithium Carbonate in Patients With Spinocerebellar Ataxia Type 3

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ClinicalTrials.gov Identifier: NCT01096082
Recruitment Status : Completed
First Posted : March 30, 2010
Last Update Posted : January 30, 2013
Sponsor:
Information provided by (Responsible Party):
Laura Bannach Jardim, Hospital de Clinicas de Porto Alegre

Tracking Information
First Submitted Date  ICMJE March 29, 2010
First Posted Date  ICMJE March 30, 2010
Last Update Posted Date January 30, 2013
Study Start Date  ICMJE May 2011
Actual Primary Completion Date December 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 9, 2012)
  • Phase 2 - Safety and tolerability of Lithium Carbonate treatment in patients with SCA3 [ Time Frame: 6 months ]
    According to the Common toxicity criteria manual, version 2.0
  • Phase 3 - Efficacy of Lithium Carbonate treatment in patients with SCA3 [ Time Frame: 12 months ]
    Application of the Neurological Examination Score for SCA 3 (NESSCA)
Original Primary Outcome Measures  ICMJE
 (submitted: March 29, 2010)
  • Safety and tolerability of Lithium Carbonate treatment in patients with SCA3 [ Time Frame: 12 months ]
    According to the Common toxicity criteria manual, version 2.0
  • Efficacy of Lithium Carbonate treatment in patients with SCA3 [ Time Frame: 12 months ]
    Application of the Scale for the Assessment and Rating of Ataxia (SARA)
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 9, 2012)
  • Efficacy of Lithium Carbonate in patients with SCA3 on neurological function, ataxic, depressive and quality of life scores [ Time Frame: 6 and 12 months ]
    Scale for the Assessment and Rating of Ataxia (SARA), 9-Hole Peg Board test, 8m walking time, PATA repetition rate, Click Test, SCA Functional Index (SCAFI), Composite Cerebellar Functional Score (CCFS), Beck Depression Inventory, Barthel Index and WHOQol
  • Effect of Lithium Carbonate treatment in peripheral levels and expression of treatment biomarkers [ Time Frame: 3 and 6 months ]
    BDNF, NSE, HDAC, GSK-3Beta
Original Secondary Outcome Measures  ICMJE
 (submitted: March 29, 2010)
  • Efficacy of Lithium Carbonate in patients with SCA3 on neurological function, ataxic, depressive and quality of life scores [ Time Frame: 12 months ]
    Neurological Examination Score for SCA 3 (NESSCA), 9-Hole Peg Board test, Beck Depression Inventory and WHOQol
  • Effect of Lithium Carbonate treatment in peripheral levels and expression of treatment biomarkers [ Time Frame: 12 months ]
    BDNF, NSE, HDAC, GSK-3Beta
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy of Lithium Carbonate in Patients With Spinocerebellar Ataxia Type 3
Official Title  ICMJE Randomized Clinical Trial to Assess the Safety and Efficacy of Lithium Carbonate in Patients With Spinocerebellar Ataxia Type 3
Brief Summary

Design: Phase II-III, double-blind, parallel, placebo controlled randomized Clinical trial

Background: Spinocerebellar ataxia type 3 (SCA-3) is an autosomal dominant adult-onset neurodegenerative disorder for which there is no current treatment. Patients will invariably become dependent from others and unable to walk during the disease course.

Hypothesis: Lithium Carbonate is safe and effective in treating neurological symptoms and improving quality of life of patients with SCA3.

Outcomes:

Primary

  • Phase 2 - To assess safety and tolerability of Lithium Carbonate in patients with SCA3 after 6 months of follow-up
  • Phase 3 (if Phase II study shows safety of therapy) - To assess efficacy of Lithium Carbonate in patients with SCA3 through the Neurological Examination Score for SCA 3 (NESSCA) after 12 months of follow-up .

Secondary

  1. - To assess efficacy on neurological function, ataxic, depressive and quality of life scores of Lithium Carbonate in patients with SCA3 through the Scale for the Assessment and Rating of Ataxia (SARA), 9-Hole Peg Board test, 8m walking time, PATA repetition rate, Click Test, SCA Functional Index (SCAFI), Composite Cerebellar Functional Score (CCFS), Beck Depression Inventory, Barthel Index and WHOQol after 6 and 12 months of follow-up.
  2. - To assess the effect of Lithium Carbonate in peripheral levels and expression of treatment biomarkers (BDNF, NSE, HDAC, GSK-3Beta)

Study Duration: 12 months

  • Final analysis of phase 2 (safety study) at 6 months with continuous monitoring until the end of phase 3 (efficacy study).
  • Preliminary analysis of efficacy on ataxia scales at 6 months of study and final analysis of phase 3 at 12 months.

Obs: A futility analysis will be performed after 12 months of therapy if no statistically significant difference between groups were found. This analysis will define if the study will continue until 18 or 24 months of follow-up or will be ended at 12 months.

Location: Hospital de Clínicas de Porto Alegre

Subjects: 60 molecularly diagnosed SCA3 patients from the outpatient unit of the Medical Genetics Service of Hospital de Clínicas de Porto Alegre

Intervention: Lithium Carbonate tablets of 300mg. Starting dose will be 300mg/day with drug titration during 49 days or until achieving the defined target lithium serum level of 0.5 to 0.8 mEq/L

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Spinocerebellar Ataxia Type 3
  • Machado Joseph Disease
Intervention  ICMJE
  • Drug: Lithium Carbonate
    300 mg tablets, starting dose 300 mg/day
  • Drug: Placebo
    Similar shape, color and taste and the same number of tablets from the experimental group
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo
  • Experimental: Lithium Carbonate
    Intervention: Drug: Lithium Carbonate
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 29, 2013)
62
Original Estimated Enrollment  ICMJE
 (submitted: March 29, 2010)
60
Actual Study Completion Date  ICMJE January 2013
Actual Primary Completion Date December 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Prior molecular diagnose of SCA3 with determined number of CAG expanded repeat.
  • Not restricted to wheelchair.
  • With disease duration between 2 and 10 years and more than 16 years old.

Exclusion Criteria:

  • Signs of cardiopathy, elevated levels of creatinine, transaminases, bilirubins more than 1.5 times the normal upper limit at baseline.
  • History of previous lithium carbonate significant adverse reaction, or drug abuse or alcoholism.
  • Disturbance of thyroid function at baseline.
  • Participation on another clinical trial less than 4 weeks before the study entrance.
  • Current use of valproic acid, memantine, neuroleptics and anticoagulants
  • If the individual (woman) did not agree in utilize a high effective contraceptive method during the study period and 3 months after the study-end.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 16 Years to 80 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Brazil
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01096082
Other Study ID Numbers  ICMJE 09-418
HCPA FIPE GPPG: 09-418 ( Other Grant/Funding Number: HCPA FIPE GPPG: 09-418 )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Laura Bannach Jardim, Hospital de Clinicas de Porto Alegre
Study Sponsor  ICMJE Hospital de Clinicas de Porto Alegre
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Laura B Jardim, MD PhD Medical Genetics Service Hospital de Clinicas de Porto Alegre
Study Director: Jonas AM Saute, MD Neurology Service Hospital de Clínicas de Porto Alegre
PRS Account Hospital de Clinicas de Porto Alegre
Verification Date January 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP