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

NCT ID: NCT01096082

Last Updated: 2013-01-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 62 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-05-31
• Study Completion Date: 2013-01-31

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

Conditions

Spinocerebellar Ataxia Type 3; Machado Joseph Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Similar shape, color and taste and the same number of tablets from the experimental group

Lithium Carbonate

Group Type: EXPERIMENTAL

Lithium Carbonate

Intervention Type: DRUG

300 mg tablets, starting dose 300 mg/day

Interventions

Lithium Carbonate

300 mg tablets, starting dose 300 mg/day

Intervention Type: DRUG

Placebo

Similar shape, color and taste and the same number of tablets from the experimental group

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospital de Clinicas de Porto Alegre

OTHER

Sponsor Role: lead

Responsible Party

Laura Bannach Jardim

MD PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Laura B Jardim, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Medical Genetics Service Hospital de Clinicas de Porto Alegre

Jonas AM Saute, MD

Role: STUDY_DIRECTOR

Neurology Service Hospital de Clínicas de Porto Alegre

Locations

Hospital de Clínicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

Countries

Brazil

References

Watase K, Gatchel JR, Sun Y, Emamian E, Atkinson R, Richman R, Mizusawa H, Orr HT, Shaw C, Zoghbi HY. Lithium therapy improves neurological function and hippocampal dendritic arborization in a spinocerebellar ataxia type 1 mouse model. PLoS Med. 2007 May;4(5):e182. doi: 10.1371/journal.pmed.0040182.

Reference Type: BACKGROUND

PMID: 17535104 (View on PubMed)

Saute JA, Rieder CR, Castilhos RM, Monte TL, Schumacher-Schuh AF, Donis KC, D'Avila R, Souza GN, Russo AD, Furtado GV, Gheno TC, Souza DO, Saraiva-Pereira ML, Portela LV, Camey S, Torman VB, Jardim LB. Planning future clinical trials in Machado Joseph disease: Lessons from a phase 2 trial. J Neurol Sci. 2015 Nov 15;358(1-2):72-6. doi: 10.1016/j.jns.2015.08.019. Epub 2015 Aug 14.

Reference Type: DERIVED

PMID: 26297649 (View on PubMed)

Saute JA, de Castilhos RM, Monte TL, Schumacher-Schuh AF, Donis KC, D'Avila R, Souza GN, Russo AD, Furtado GV, Gheno TC, de Souza DO, Portela LV, Saraiva-Pereira ML, Camey SA, Torman VB, de Mello Rieder CR, Jardim LB. A randomized, phase 2 clinical trial of lithium carbonate in Machado-Joseph disease. Mov Disord. 2014 Apr;29(4):568-73. doi: 10.1002/mds.25803. Epub 2014 Jan 7.

Reference Type: DERIVED

PMID: 24399647 (View on PubMed)

Other Identifiers

HCPA FIPE GPPG: 09-418

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

09-418

Identifier Type: -

Identifier Source: org_study_id