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

Sponsor

Hospital de Clinicas de Porto Alegre (Other)

Overall Status

Completed

CT.gov ID

NCT01096082

Collaborator

(none)

Enrollment

Location

Arms

20.1

Duration (Months)

3.1

Patients Per Site Per Month

Study Details

Study Description

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

- 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.
- 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 or Disease	Intervention/Treatment	Phase
Spinocerebellar Ataxia Type 3 Machado Joseph Disease	Drug: Lithium Carbonate Drug: Placebo	Phase 2/Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

62 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, 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

Study Start Date :

May 1, 2011

Actual Primary Completion Date :

Dec 1, 2012

Actual Study Completion Date :

Jan 1, 2013

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Phase 2 - Safety and tolerability of Lithium Carbonate treatment in patients with SCA3 [6 months]
According to the Common toxicity criteria manual, version 2.0
Phase 3 - Efficacy of Lithium Carbonate treatment in patients with SCA3 [12 months]
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 [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 [3 and 6 months]
BDNF, NSE, HDAC, GSK-3Beta

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	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