Lithium in Multiple System Atrophy

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

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.

Official Title
-----------------
A Double-blind, Randomized, Placebo-controlled Clinical Trial to Assess Efficacy, Safety and Tolerability of Lithium in Multiple System Atrophy.

Conditions
-----------------
Multiple System Atrophy

Intervention / Treatment
-----------------
* Drug: Lithium Carbonate
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Clinical diagnosis of probable MSA (Gilman, et al. 2008) Age ≥18, <80 Exclusion Criteria: 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
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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>Placebo comparator | Drug: Placebo<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Endpoint of the Study Will be the Difference in Number and Relative Frequency of Severe Adverse Events (SAE) and Non Severe Adverse Events (nSAE) Recorded During the Study, Between Treatment and Placebo Group. | Number of Adverse Events and their relative frequency in treatment groups was analyzed | the endpoint will be recorded at all visits | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Outcome Will be the Unified Multiple System Atrophy Rating Scale (UMSARS). 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 Unified Multiple System Atrophy Rating Scale (UMSARS). Statistical Analysis Will be Performed to Compare the Effect of Treatment on Both Groups. |  | 24 weeks | 
| Secondary Outcome Will be the Unified Multiple System Atrophy Rating Scale (UMSARS). 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
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
MSA, Lithium, Lithium carbonate, MSA-P, MSA-C