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

NCT01096082 | Completed Phase 2

• 2 other identifiers: 09-418HCPA FIPE GPPG: 09-418
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

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)
• 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

Keywords

spinocerebellar ataxia; Treatment; Lithium carbonate

Outcome Measures

Primary Outcomes (2)

• 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

• Phase 3 - Efficacy of Lithium Carbonate treatment in patients with SCA3

  Application of the Neurological Examination Score for SCA 3 (NESSCA)

  12 months

Secondary Outcomes (2)

• Efficacy of Lithium Carbonate in patients with SCA3 on neurological function, ataxic, depressive and quality of life scores

  6 and 12 months

• Effect of Lithium Carbonate treatment in peripheral levels and expression of treatment biomarkers

  3 and 6 months

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Lithium Carbonate

EXPERIMENTAL

Drug: Lithium Carbonate

Interventions

Lithium Carbonate DRUG

300 mg tablets, starting dose 300 mg/day

Lithium Carbonate

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 16 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hospital de Clinicas de Porto Alegre: lead

Study Sites (1)

Hospital de Clínicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, 90035-903, Brazil

Location

Related Publications (3)

• 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.

  PMID: 17535104 BACKGROUND

• 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.

  PMID: 26297649 DERIVED

• 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.

  PMID: 24399647 DERIVED

MeSH Terms

Conditions

Machado-Joseph Disease; Spinocerebellar Ataxias

Interventions

Lithium Carbonate

Condition Hierarchy (Ancestors)

Cerebellar Ataxia; Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Spinocerebellar Degenerations; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Ataxia; Dyskinesias; Neurologic Manifestations; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Carbonates; Alkalies; Inorganic Chemicals; Carbonic Acid; Carbon Compounds, Inorganic; Lithium Compounds

Study Officials

• Laura B Jardim, MD PhD

  Medical Genetics Service Hospital de Clinicas de Porto Alegre

  PRINCIPAL INVESTIGATOR

• Jonas AM Saute, MD

  Neurology Service Hospital de Clínicas de Porto Alegre

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD PhD

Study Record Dates

• First Submitted: March 29, 2010
• First Posted: March 30, 2010
• Study Start: May 1, 2011
• Primary Completion: December 1, 2012
• Study Completion: January 1, 2013
• Last Updated: January 30, 2013

Record last verified: 2013-01

Locations

BR (1)