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

January 29, 2013 updated by: Laura Bannach Jardim, Hospital de Clinicas de Porto Alegre

Randomized Clinical Trial to Assess the Safety and Efficacy of Lithium Carbonate in Patients With Spinocerebellar Ataxia Type 3

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

62

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Brazil
    • Rio Grande do Sul
      • Porto Alegre, Rio Grande do Sul, Brazil, 90035-903
        • Hospital de Clinicas de Porto Alegre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 80 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
6 months
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)
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
6 and 12 months
Effect of Lithium Carbonate treatment in peripheral levels and expression of treatment biomarkers
Time Frame: 3 and 6 months
BDNF, NSE, HDAC, GSK-3Beta
3 and 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2011

Primary Completion (Actual)

December 1, 2012

Study Completion (Actual)

January 1, 2013

Study Registration Dates

First Submitted

March 29, 2010

First Submitted That Met QC Criteria

March 29, 2010

First Posted (Estimate)

March 30, 2010

Study Record Updates

Last Update Posted (Estimate)

January 30, 2013

Last Update Submitted That Met QC Criteria

January 29, 2013

Last Verified

January 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 09-418
  • HCPA FIPE GPPG: 09-418 (Other Grant/Funding Number: HCPA FIPE GPPG: 09-418)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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