Multiple System Atrophy
Conditions
Keywords
MSA, Lithium, Lithium carbonate, MSA-P, MSA-C
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.
Interventions
DRUGLithium 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.
DRUGPlacebo
Sponsors
Federico II University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | the endpoint will be recorded at all visits | Number of Adverse Events and their relative frequency in treatment groups was analyzed |
Secondary
| Measure | 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 |
Countries
Italy
Participant flow
Recruitment details
Patients were recruited through our outpatient clinic. Recruitment started the 4th June 2010 and the trial was stopped the 22nd of August 2011
Pre-assignment details
Patients were screened prior to randomization, no patients were excluded.
Participants by arm
| Arm | Count |
|---|---|
| Lithium CARBONATE 150 or 300 mg 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. | 4 |
| Placebo 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. | 5 |
| Total | 9 |
Baseline characteristics
| Characteristic | Total | Lithium CARBONATE 150 or 300 mg | Placebo |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 2 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 2 Participants | 4 Participants |
| Age, Continuous | 64 years STANDARD_DEVIATION 5 | 65 years STANDARD_DEVIATION 5 | 64 years STANDARD_DEVIATION 6 |
| Region of Enrollment Italy | 9 participants | 4 participants | 5 participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 0 Participants |
| Sex: Female, Male Male | 7 Participants | 2 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 4 | 3 / 5 |
| serious Total, serious adverse events | 4 / 4 | 1 / 5 |
Outcome results
Primary
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
Time frame: the endpoint will be recorded at all visits
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lithium CARBONATE 150 or 300 mg | 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. | 58 number of AEs |
| Placebo | 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. | 21 number of AEs |
Secondary
Effect of Lithium on Quality of Life Will be Assessed With the EQ-5D Scale.
Time frame: 48 weeks
Secondary
Effect of Lithium on Quality of Life Will be Assessed With the EQ-5D Scale.
Time frame: 0 weeks
Secondary
Effect of Lithium on Quality of Life Will be Assessed With the EQ-5D Scale.
Time frame: 24 weeks
Secondary
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.
Time frame: 0 weeks
Secondary
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.
Time frame: 48 weeks
Secondary
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.
Time frame: 48 weeks
Secondary
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.
Time frame: 0 weeks
Secondary
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.
Time frame: 24 weeks
Secondary
The Effect of Lithium on Mood Will be Explored With the Beck Depression Inventory.
Time frame: 0 weeks
Secondary
The Effect of Lithium on Mood Will be Explored With the Beck Depression Inventory.
Time frame: 24 weeks
Secondary
The Effect of Lithium on Mood Will be Explored With the Beck Depression Inventory.
Time frame: 48 weeks