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

Spinocerebellar Ataxia Type 3 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01096082
• Other study ID #: 09-418
• Secondary ID: HCPA FIPE GPPG:
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: March 29, 2010
• Last updated: January 29, 2013
• Start date: May 2011
• Est. completion date: January 2013

Study information

• Verified date: January 2013
• Source: Hospital de Clinicas de Porto Alegre
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: National Committee of Ethics in Research
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 62
• Est. completion date: January 2013
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years to 80 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ataxia
• Cerebellar Ataxia
• Machado Joseph Disease
• Machado-Joseph Disease
• Spinocerebellar Ataxia Type 3
• Spinocerebellar Ataxias
• Spinocerebellar Degenerations

Intervention

Drug:
• Lithium Carbonate
300 mg tablets, starting dose 300 mg/day
• Placebo
Similar shape, color and taste and the same number of tablets from the experimental group

Locations

Country	Name	City	State
Brazil	Hospital de Clínicas de Porto Alegre	Porto Alegre	Rio Grande do Sul

Sponsors (1)

Lead Sponsor	Collaborator
Hospital de Clinicas de Porto Alegre

Country where clinical trial is conducted

Brazil, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 2 - Safety and tolerability of Lithium Carbonate treatment in patients with SCA3	According to the Common toxicity criteria manual, version 2.0	6 months	Yes
Primary	Phase 3 - Efficacy of Lithium Carbonate treatment in patients with SCA3	Application of the Neurological Examination Score for SCA 3 (NESSCA)	12 months	No
Secondary	Efficacy of Lithium Carbonate in patients with SCA3 on neurological function, ataxic, depressive and quality of life scores	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	No
Secondary	Effect of Lithium Carbonate treatment in peripheral levels and expression of treatment biomarkers	BDNF, NSE, HDAC, GSK-3Beta	3 and 6 months	No