Spinocerebellar Ataxia Type 3Phase 2/3NCT01096082
Safety and Efficacy of Lithium Carbonate in Patients With Spinocerebellar Ataxia Type 3
A Phase 2/3 study testing Lithium Carbonate in people with Spinocerebellar Ataxia Type 3 and Machado Joseph Disease, run by Hospital de Clinicas de Porto Alegre at 1 site in Brazil.
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. Read more about this study
- Who is it for?
- Ages 16 to 80 years
- Conditions the study is for
- Spinocerebellar Ataxia Type 3, Machado Joseph Disease
- What is being tested?
- Lithium Carbonate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 62 participants
- Where
- 1 siteBrazil
- Study dates
- May 2011to Jan 2013
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 80 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Brazil1 site
Hospital de Clínicas de Porto Alegre
Porto Alegre, Rio Grande do Sul, 90035-903
About this study
Official title: 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.
Read more
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
- Being tested
- Lithium Carbonate, Placebo
- Keywords
- spinocerebellar ataxia, Treatment, Lithium carbonate
- Medical subject headings
- Machado-Joseph Disease, Spinocerebellar Ataxias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lithium CarbonateDrug
300 mg tablets, starting dose 300 mg/day
PlaceboDrug
Similar shape, color and taste and the same number of tablets from the experimental group
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
| Lithium Carbonate | Experimental | Not described Receives: Drug: Lithium Carbonate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 2 - Safety and tolerability of Lithium Carbonate treatment in patients with SCA3
According to the Common toxicity criteria manual, version 2.0
Measured: 6 months
Phase 3 - Efficacy of Lithium Carbonate treatment in patients with SCA3
Application of the Neurological Examination Score for SCA 3 (NESSCA)
Measured: 12 months
Secondary outcomes (2)
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
Measured: 6 and 12 months
Effect of Lithium Carbonate treatment in peripheral levels and expression of treatment biomarkers
BDNF, NSE, HDAC, GSK-3Beta
Measured: 3 and 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Mar 2010 (estimated)
- Study startMay 2011
- Primary completionDec 2012
- Study completionJan 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Spinocerebellar Ataxia Type 3Studies of the same condition, open and under way.
- More trials run by Hospital de Clinicas de Porto AlegreThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 62 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospital de Clinicas de Porto Alegre
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Laura Bannach Jardim, Hospital de Clinicas de Porto Alegre
- Investigators
- Laura B Jardim, MD PhD, Principal investigator, Medical Genetics Service Hospital de Clinicas de Porto AlegreJonas AM Saute, MD, Study director, Neurology Service Hospital de Clínicas de Porto Alegre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01096082
- Sponsor's protocol ID
- 09-418
- Other IDs
- HCPA FIPE GPPG: 09-418
- Status last verified
- Jan 2013
- First submitted
- 29 Mar 2010
- Last updated
- 30 Jan 2013
- Results posted
- No
Publications
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.
PubMed 17535104Saute 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.
PubMed 26297649Saute 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.
PubMed 24399647
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Clinical Trial to Assess the Safety and Efficacy of Lithium Carbonate in Patients With Spinocerebellar Ataxia Type 3
- ClinicalTrials.gov ID
- NCT01096082
- Acronym / sponsor ID
- 09-418
- Keywords
- spinocerebellar ataxia, Treatment, Lithium carbonate
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 62 participants (actual)
- Lead sponsor
- Hospital de Clinicas de Porto AlegreUniversity, hospital or other
- Study start
- May 2011
- Primary completion
- Dec 2012 (actual)
- Study completion
- Jan 2013 (actual)
- First posted
- 30 Mar 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placebo |
| Lithium Carbonate | Experimental | Drug: Lithium Carbonate |
Who may qualify
- Ages
- 16 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lithium Carbonate300 mg tablets, starting dose 300 mg/day | Drug | Lithium Carbonate |
| PlaceboSimilar shape, color and taste and the same number of tablets from the experimental group | Drug | Placebo |
Primary outcome
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
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)
2 secondary outcomes
Efficacy of Lithium Carbonate in patients with SCA3 on neurological function, ataxic, depressive and quality of life scores
Time frame: 6 and 12 months
Effect of Lithium Carbonate treatment in peripheral levels and expression of treatment biomarkers
Time frame: 3 and 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2013.
- Background: PubMed 17535104Watase 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.
- Derived from this study: PubMed 26297649Saute 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.
- Derived from this study: PubMed 24399647Saute 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Laura B Jardim, MD PhD principal investigator
Medical Genetics Service Hospital de Clinicas de Porto Alegre
Jonas AM Saute, MD study director
Neurology Service Hospital de Clínicas de Porto Alegre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Lithium Carbonate in people with Spinocerebellar Ataxia Type 3 and Machado Joseph Disease, run by Hospital de Clinicas de Porto Alegre at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Jan 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase 2 - Safety and tolerability of Lithium Carbonate treatment in patients with SCA3 (time frame: 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01096082, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jan 2013.