Safety and Tolerability of Lithium in Spinocerebellar Ataxia 2 (SCA2)

Study Overview
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Brief Summary
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The purpose of this study is to determine safety and tolerability of the treatment with lithium in Spinocerebellar Ataxia 2. Moreover, clinical symptoms, neuronal loss, quality of life and depressive symptoms, will be considered to further investigate the effect of lithium therapy.

Detailed Description
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Patients will be progressively enrolled in the study and undergo a screening visit to test for inclusion/exclusion criteria. Patients will then be randomized to receive either Lithium carbonate or placebo. Patients will visit study center at 2, 4, 8, 12, 24, 36 and 48 weeks, for endpoint and laboratory assessments.

Official Title
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Randomized, Placebo-controlled Trial to Test Safety, Tolerability and Efficacy of Lithium Carbonate in Spinocerebellar Ataxia 2

Conditions
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SPINOCEREBELLAR ATAXIA 2

Intervention / Treatment
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* Drug: LITHIUM CARBONATE


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Molecular diagnosis of SCA2 (≥34 CAG in the ataxin-2 gene) Age ≥18, <80 SARA score ≥8 Exclusion Criteria: SARA score >32 Heart failure Liver disease Kidney failure Thyroid disease Sick sinus syndrome and/or significant ECG alterations Hyposodemia Treatment with diuretics Treatment with haloperidol and/or other antipsychotics Treatment with NSAIDs or corticosteroids Treatment with ACE inhibitors Treatment with aminophyllines Treatment with mannitol Pregnancy and/or breastfeeding Acute diseases that might interfere with the trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LITHIUM CARBONATE 150 and/or 300 mg<br> | Drug: LITHIUM CARBONATE<br>* Lithium Carbonate will be dosed based on lithiemy, which will be in the range 0.9-1.2 mEq/L. Maximum allowed dose will be 1500mg/day.<br>|
| Placebo Comparator: PLACEBO<br> | Drug: LITHIUM CARBONATE<br>* Lithium Carbonate will be dosed based on lithiemy, which will be in the range 0.9-1.2 mEq/L. Maximum allowed dose will be 1500mg/day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary endpoint of the study will be the difference in the number and frequency of Severe Adverse Events (SAE) and Non Severe Adverse Events (nSAE) recorded during the study, between treatment and placebo group. | Adverse events and Severe Adverse events will be recorded during the trial at each visit starting from Baseline to Visit 8 at 48 weeks of treatment. | the endpoint will be recorded at all visits | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary outcome will be the Scale for the Assessment and Rating of Ataxia (SARA). Statistical analysis will be performed to compare the effect of treatment on both groups. |  | 0 weeks | 
| Micro- and macrostructural Magnetic Resonance parameters will be compared before and after treatment. This will include Voxel Based Morphometry, resting functional MRI, Diffusion tensor imaging and MRI spectroscopy. |  | 0 weeks | 
| The effect of Lithium on mood will be explored with the Beck depression inventory. |  | 0 weeks | 
| Effect of Lithium on quality of life will be assessed with the EQ-5D scale. |  | 0 weeks | 
| Secondary outcome will be the Scale for the Assessment and Rating of Ataxia (SARA). Statistical analysis will be performed to compare the effect of treatment on both groups. |  | 24 weeks | 
| Secondary outcome will be the Scale for the Assessment and Rating of Ataxia (SARA). Statistical analysis will be performed to compare the effect of treatment on both groups. |  | 48 weeks | 
| Micro- and macrostructural Magnetic Resonance parameters will be compared before and after treatment. This will include Voxel Based Morphometry, resting functional MRI, Diffusion tensor imaging and MRI spectroscopy. |  | 48 weeks | 
| The effect of Lithium on mood will be explored with the Beck depression inventory. |  | 24 weeks | 
| The effect of Lithium on mood will be explored with the Beck depression inventory. |  | 48 weeks | 
| Effect of Lithium on quality of life will be assessed with the EQ-5D scale. |  | 24 weeks | 
| Effect of Lithium on quality of life will be assessed with the EQ-5D scale. |  | 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SCA2, Lithium