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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Laura Bannach Jardim, Hospital de Clinicas de Porto Alegre
ClinicalTrials.gov Identifier:
NCT01096082
First received: March 29, 2010
Last updated: January 29, 2013
Last verified: January 2013
  Purpose

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


Condition Intervention Phase
Spinocerebellar Ataxia Type 3
Machado Joseph Disease
Drug: Lithium Carbonate
Drug: Placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomized Clinical Trial to Assess the Safety and Efficacy of Lithium Carbonate in Patients With Spinocerebellar Ataxia Type 3

Resource links provided by NLM:


Further study details as provided by Hospital de Clinicas de Porto Alegre:

Primary Outcome Measures:
  • Phase 2 - Safety and tolerability of Lithium Carbonate treatment in patients with SCA3 [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    Application of the Neurological Examination Score for SCA 3 (NESSCA)


Secondary Outcome Measures:
  • Efficacy of Lithium Carbonate in patients with SCA3 on neurological function, ataxic, depressive and quality of life scores [ Time Frame: 6 and 12 months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    BDNF, NSE, HDAC, GSK-3Beta


Enrollment: 62
Study Start Date: May 2011
Study Completion Date: January 2013
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo Drug: Placebo
Similar shape, color and taste and the same number of tablets from the experimental group
Experimental: Lithium Carbonate Drug: Lithium Carbonate
300 mg tablets, starting dose 300 mg/day

  Eligibility

Ages Eligible for Study:   16 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01096082

Locations
Brazil
Hospital de Clínicas de Porto Alegre
Porto Alegre, Rio Grande do Sul, Brazil, 90035-903
Sponsors and Collaborators
Hospital de Clinicas de Porto Alegre
Investigators
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
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Laura Bannach Jardim, MD PhD, Hospital de Clinicas de Porto Alegre
ClinicalTrials.gov Identifier: NCT01096082     History of Changes
Other Study ID Numbers: 09-418, HCPA FIPE GPPG: 09-418
Study First Received: March 29, 2010
Last Updated: January 29, 2013
Health Authority: Brazil: National Committee of Ethics in Research

Keywords provided by Hospital de Clinicas de Porto Alegre:
spinocerebellar ataxia
Treatment
Lithium carbonate

Additional relevant MeSH terms:
Ataxia
Spinocerebellar Ataxias
Spinocerebellar Degenerations
Cerebellar Ataxia
Cerebellar Diseases
Machado-Joseph Disease
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Brain Diseases
Central Nervous System Diseases
Spinal Cord Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Lithium
Lithium Carbonate
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs
Antimanic Agents
Antidepressive Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 20, 2014