LAMU: Lithium in Multiple System Atrophy

• Sponsor: Federico II University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00997672
• Collaborator: (none)
• Enrollment: 10
• Location: 1
• Arms: 2
• Duration (Months): 22
• Patients Per Site Per Month: 0.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Multiple System Atrophy	Drug: Lithium Carbonate; Drug: Placebo	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Double-blind, Randomized, Placebo-controlled Clinical Trial to Assess Efficacy, Safety and Tolerability of Lithium in Multiple System Atrophy.
• Study Start Date: Oct 1, 2009
• Actual Primary Completion Date: Aug 1, 2011
• Actual Study Completion Date: Aug 1, 2011

Arms and Interventions

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 Placebo comparator	Drug: Placebo

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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]

2. 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]

3. The Effect of Lithium on Mood Will be Explored With the Beck Depression Inventory. [0 weeks]

4. Effect of Lithium on Quality of Life Will be Assessed With the EQ-5D Scale. [0 weeks]

5. 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]

6. 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]

7. 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]

8. The Effect of Lithium on Mood Will be Explored With the Beck Depression Inventory. [24 weeks]

9. The Effect of Lithium on Mood Will be Explored With the Beck Depression Inventory. [48 weeks]

10. Effect of Lithium on Quality of Life Will be Assessed With the EQ-5D Scale. [24 weeks]

11. Effect of Lithium on Quality of Life Will be Assessed With the EQ-5D Scale. [48 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dipartimento di Scienze Neurologiche	Napoli		Italy	80131

Sponsors and Collaborators

• Federico II University

Investigators

• Principal Investigator: Alessandro Filla, MD, University Federico II

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

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

Publications

• Gilman S, Wenning GK, Low PA, Brooks DJ, Mathias CJ, Trojanowski JQ, Wood NW, Colosimo C, Dürr A, Fowler CJ, Kaufmann H, Klockgether T, Lees A, Poewe W, Quinn N, Revesz T, Robertson D, Sandroni P, Seppi K, Vidailhet M. Second consensus statement on the diagnosis of multiple system atrophy. Neurology. 2008 Aug 26;71(9):670-6. doi: 10.1212/01.wnl.0000324625.00404.15.

• Responsible Party: Alessandro Filla, Principal Investigator, Federico II University
• ClinicalTrials.gov Identifier: NCT00997672
• Other Study ID Numbers: MSA_LITIO_13; Eudract n°2009-016377-15
• First Posted: Oct 19, 2009
• Last Update Posted: Feb 3, 2014
• Last Verified: Dec 1, 2013

• Keywords provided by Alessandro Filla, Principal Investigator, Federico II University: MSA; Lithium; Lithium carbonate; MSA-P; MSA-C
• Additional relevant MeSH terms: Multiple System Atrophy; Shy-Drager Syndrome; Atrophy; Lithium Carbonate

Study Results

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 Detail	Patients were screened prior to randomization, no patients were excluded.

Arm/Group Title	Lithium CARBONATE 150 or 300 mg	Placebo
Arm/Group Description	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
Period Title: Overall Study
STARTED	4	5
COMPLETED	0	1
NOT COMPLETED	4	4

Baseline Characteristics

Arm/Group Title	Lithium CARBONATE 150 or 300 mg	Placebo	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	4	5	9
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	2 50%	4 80%	6 66.7%
>=65 years	2 50%	1 20%	3 33.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65 (5)	64 (6)	64 (5)
Sex: Female, Male (Count of Participants)
Female	2 50%	0 0%	2 22.2%
Male	2 50%	5 100%	7 77.8%
Region of Enrollment (participants) [Number]
Italy	4 100%	5 100%	9 100%

Outcome Measures

1. Primary Outcome

Title	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.
Description	Number of Adverse Events and their relative frequency in treatment groups was analyzed
Time Frame	the endpoint will be recorded at all visits

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lithium CARBONATE 150 or 300 mg	Placebo
Arm/Group Description	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.	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.
Measure Participants	4	5
Number [number of AEs]	58	21

2. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	The Effect of Lithium on Mood Will be Explored With the Beck Depression Inventory.
Time Frame	0 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Effect of Lithium on Quality of Life Will be Assessed With the EQ-5D Scale.
Time Frame	0 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

9. Secondary Outcome

Title	The Effect of Lithium on Mood Will be Explored With the Beck Depression Inventory.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

10. Secondary Outcome

Title	The Effect of Lithium on Mood Will be Explored With the Beck Depression Inventory.
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

11. Secondary Outcome

Title	Effect of Lithium on Quality of Life Will be Assessed With the EQ-5D Scale.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

12. Secondary Outcome

Title	Effect of Lithium on Quality of Life Will be Assessed With the EQ-5D Scale.
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	Lithium CARBONATE 150 or 300 mg		Placebo
Arm/Group Description	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.		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.
All Cause Mortality
	Lithium CARBONATE 150 or 300 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Lithium CARBONATE 150 or 300 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/4 (100%)		1/5 (20%)
Cardiac disorders
Death	1/4 (25%)	1	1/5 (20%)	1
Cardiovascular failure	1/4 (25%)	1	1/5 (20%)	1
Infections and infestations
Fever	1/4 (25%)	1	0/5 (0%)	0
Inguinal abscess	1/4 (25%)	1	0/5 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pulmonary infection	0/4 (0%)	0	1/5 (20%)	1
Other (Not Including Serious) Adverse Events
	Lithium CARBONATE 150 or 300 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/4 (100%)		3/5 (60%)
Gastrointestinal disorders
diarrhea	2/4 (50%)	4	2/5 (40%)	5
gastroaesophageal reflux	1/4 (25%)	4	2/5 (40%)	5
Musculoskeletal and connective tissue disorders
joint rigidity	2/4 (50%)	4	1/5 (20%)	5
Nervous system disorders
Lower limbs weakness	3/4 (75%)	4	3/5 (60%)	5
sleepiness	1/4 (25%)	4	2/5 (40%)	5
Renal and urinary disorders
Incontinence	1/4 (25%)	4	3/5 (60%)	5
Cystitis	2/4 (50%)	4	1/5 (20%)	5
Respiratory, thoracic and mediastinal disorders
pulmonitis	1/4 (25%)	4	1/5 (20%)	5

Limitations/Caveats

Limitation of the study is small sample size of nine randomized patients. This may have determined uneven distribution of AEs due to random variation. Taking into account these limitations, we do not encourage future studies with lithium in MSA.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.