Safety and Tolerability of Lithium in Spinocerebellar Ataxia 2 (SCA2) (LISCA2)

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

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.

Study Overview

• Status: Completed
• Conditions: SPINOCEREBELLAR ATAXIA 2
• Intervention / Treatment: Drug: LITHIUM CARBONATE

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Napoli, Italy, 80131
    • Dipartimento Di Scienze Neurologiche

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: LITHIUM CARBONATE 150 and/or 300 mg	Drug: LITHIUM CARBONATE; 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.
PLACEBO_COMPARATOR: PLACEBO	Drug: LITHIUM CARBONATE; 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.

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Federico II University

Publications and helpful links

Helpful Links

• University Federico II
• AOU Policlinico "Federico II"
• AISA sez. Campania

Study record dates

Study Major Dates

• Study Start: October 1, 2009
• Primary Completion (ACTUAL): November 1, 2012
• Study Completion (ACTUAL): November 1, 2012

Study Registration Dates

• First Submitted: October 16, 2009
• First Submitted That Met QC Criteria: October 19, 2009
• First Posted (ESTIMATE): October 20, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): January 8, 2013
• Last Update Submitted That Met QC Criteria: January 7, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Keywords: Lithium; SCA2
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Genetic Diseases, Inborn; Neurodegenerative Diseases; Dyskinesias; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Cerebellar Diseases; Ataxia; Cerebellar Ataxia; Spinocerebellar Ataxias; Spinocerebellar Degenerations; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Enzyme Inhibitors; Tranquilizing Agents; Psychotropic Drugs; Antidepressive Agents; Antimanic Agents; Lithium Carbonate
• Other Study ID Numbers: SCA_LITIO_12; EUDRACT N°2009-016317-20