A Multi-Center Controlled Screening Trial of Safety and Efficacy of Lithium Carbonate in Subjects With Amyotrophic Lateral Sclerosis (ALS)
Study Details
Study Description
Brief Summary
This is a Phase II screening study of lithium carbonate in ALS. The purpose of this study is to find out if lithium carbonate is safe to be used in people with ALS and if it can slow the progression of the disease. Since there is no placebo in this study, all patients will be taking lithium carbonate.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
This is a Phase II Screening study. There is no placebo (inactive or 'fake' drug) in this study, meaning that all participants will be taking lithium carbonate. The purpose of this study is to find out if lithium carbonate is safe to be used in people with ALS and if it can slow the progression of the disease.
A recent article was published in a highly regarded medical journal that showed a positive effect of lithium carbonate on an ALS type mouse. The researchers then studied a very small number of people with ALS, giving 16 people lithium carbonate with riluzole and giving 28 people only riluzole. The people who took lithium remained stronger for a considerably longer period of time. However, the study was very small and we cannot really tell if lithium works unless a larger study is performed. It is not well understood why lithium carbonate might be helpful but it is believed that it may play a role in protecting the motor nerves from the damage of ALS.
If you choose to participate, you will need to go to your study clinic for research study visits 7 times in one year and you will have 4 telephone interviews during that time. These visits and phone calls could take up to 17 hours in total.
Caution: Lithium is an FDA approved drug used for some psychiatric disorders. It is not FDA approved for ALS. Lithium has many potentially serious side effects and must only be taken under close supervision of your physician.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: lithium carbonate
|
Drug: lithium carbonate
The dosage of lithium carbonate will be adjusted for each individual. The maximum dose is 450mg/day.
|
Outcome Measures
Primary Outcome Measures
- Change in Monthly Rate of Decline in ALSFRS-R (Amyotrophic Lateral Sclerosis Functional Rating Score - Revised) [Baseline, Month 1,3,4.5,6,7.5,9,10.5,12,13]
This questionnaire has 12 questions about the patient's ability to complete certain daily activities. There are three questions each about the mouth area, arms, legs, and breathing. A normal score is 48 with each question scored at 0 (worst) to 4 (normal function). In research studies, the change in slope is measured in number of points changed per month. Maximum possible=48 (normal) Minimum=0 (severe dysfunction)
Secondary Outcome Measures
- Vital Capacity [Screen, Baseline, Month 1,3,6,9,12]
Vital Capacity (VC) is a breathing test in which the patient is asked to take a deep breath and then blow out all of the breath through a tube. The volume is measured in number of liters. It is converted to a percent predicted for the patient's age, height, and gender.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Clinical diagnosis of laboratory-supported probable, probable, or definite ALS
-
Vital capacity of at least 75% of predicted
-
Onset of weakness within 3 years prior to enrollment
-
If patients are on riluzole, they must be on a stable dose for at least 30 days prior to baseline visit
-
Women of childbearing potential must be surgically sterile or using an effective method of birth control and have a negative pregnancy test
-
Willing and able to give informed consent
Exclusion Criteria:
-
Diagnosis of other neurodegenerative disease
-
Need tracheotomy ventilation or non-invasive ventilation 23 or more hours/day
-
Clinically significant history of any unstable medical condition in past 30 days
-
History of renal
-
History of liver disease
-
Current pregnancy or lactation
-
Use of lithium within thirty days of enrollment
-
Significantly limited mental capacity
-
History of recent drug or alcohol abuse
-
Use of any investigational drug within 30 days prior to enrollment
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Mayo Clinic | Scottsdale | Arizona | United States | 85259 |
| 2 | UCLA Neuromuscular Research Center | Los Angeles | California | United States | 90095 |
| 3 | UC Irvine MDA/ALS & Neuromuscular Center | Orange | California | United States | 92868 |
| 4 | California Pacific Medical Center | San Francisco | California | United States | 94115 |
| 5 | Kansas University Medical Center | Kansas City | Kansas | United States | 66160 |
| 6 | Washington University Department of Neurology | Saint Louis | Missouri | United States | 63110 |
| 7 | Providence ALS Clinic | Portland | Oregon | United States | 97213 |
| 8 | University of Pennsylvania Neurological Institute | Philadelphia | Pennsylvania | United States | 19107 |
| 9 | Methodist Neurological Institute | Houston | Texas | United States | 77030 |
| 10 | University of Utah Clinical Neurosciences Center | Salt Lake City | Utah | United States | 84132 |
Sponsors and Collaborators
- Forbes Norris MDA/ALS Research Center
- Muscular Dystrophy Association
Investigators
- Study Director: Robert G Miller, MD, California Pacific Medical Center
Study Documents (Full-Text)
None provided.More Information
Publications
- 28.013
Study Results
Participant Flow
| Recruitment Details | Patients were enrolled between May 2008 and February 2009. Inclusion criteria were a diagnosis of probable or definite ALS (12), age 21-85 years, forced vital capacity (FVC) greater than or equal to 75% of predicted, and onset of weakness within 3 years. Patients taking riluzole were on a stable dose for at least 30 days. |
|---|---|
| Pre-assignment Detail | This was an open label single-arm Phase II screening trail. All enrolled subjects (n=109) were treated. Their results were compared with placebo subjects from an historical database of ALS placebo patients from recent studies (n=249). Thus the number enrolled (n=109) does not equal the total number of subjects (n=358). Enrolled subjects started lithium carbonate at 150 mg twice daily. If subjects did not tolerate a dose it was tapered by 150 mg increments to the maximum tolerated dosage. |
| Arm/Group Title | Treatment | Control |
|---|---|---|
| Arm/Group Description | 109 subjects were assigned to treatment with lithium carbonate | 249 placebo subjects from previous clinical trials |
| Period Title: Overall Study | ||
| STARTED | 109 | 249 |
| COMPLETED | 78 | 162 |
| NOT COMPLETED | 31 | 87 |
Baseline Characteristics
| Arm/Group Title | Lithium Carbonate | Historical Controls | Total |
|---|---|---|---|
| Arm/Group Description | Total of all reporting groups | ||
| Overall Participants | 109 | 249 | 358 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
56.2
(11.7)
|
57.6
(11.0)
|
57.2
(11.2)
|
| Age, Customized (participants) [Number] | |||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
84
77.1%
|
186
74.7%
|
270
75.4%
|
| >=65 years |
25
22.9%
|
63
25.3%
|
88
24.6%
|
| 18 to 75 years |
109
100%
|
249
100%
|
358
100%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
38
34.9%
|
83
33.3%
|
121
33.8%
|
| Male |
71
65.1%
|
166
66.7%
|
237
66.2%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
109
100%
|
249
100%
|
358
100%
|
Outcome Measures
| Title | Change in Monthly Rate of Decline in ALSFRS-R (Amyotrophic Lateral Sclerosis Functional Rating Score - Revised) |
|---|---|
| Description | This questionnaire has 12 questions about the patient's ability to complete certain daily activities. There are three questions each about the mouth area, arms, legs, and breathing. A normal score is 48 with each question scored at 0 (worst) to 4 (normal function). In research studies, the change in slope is measured in number of points changed per month. Maximum possible=48 (normal) Minimum=0 (severe dysfunction) |
| Time Frame | Baseline, Month 1,3,4.5,6,7.5,9,10.5,12,13 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Lithium Carbonate | Historical Controls |
|---|---|---|
| Arm/Group Description | ||
| Measure Participants | 109 | 249 |
| Mean (95% Confidence Interval) [points per month] |
1.20
|
1.01
|
| Title | Vital Capacity |
|---|---|
| Description | Vital Capacity (VC) is a breathing test in which the patient is asked to take a deep breath and then blow out all of the breath through a tube. The volume is measured in number of liters. It is converted to a percent predicted for the patient's age, height, and gender. |
| Time Frame | Screen, Baseline, Month 1,3,6,9,12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Lithium Carbonate | Control |
|---|---|---|
| Arm/Group Description | Treatment arm | Placebo arm |
| Measure Participants | 109 | 249 |
| Mean (95% Confidence Interval) [Decline in the percent predicted/month] |
2.84
|
2.91
|
Adverse Events
| Time Frame | Adverse events were recorded for the duration of the trial (1 year). | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Lithium Carbonate | Historical Controls | ||
| Arm/Group Description | Treated Patients | Placebo Patients | ||
All Cause Mortality |
||||
| Lithium Carbonate | Historical Controls | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 14/109 (12.8%) | 44/249 (17.7%) | ||
Serious Adverse Events |
||||
| Lithium Carbonate | Historical Controls | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 62/109 (56.9%) | 91/249 (36.5%) | ||
| Gastrointestinal disorders | ||||
| Gastrointestinal | 17/109 (15.6%) | 17 | 23/249 (9.2%) | 23 |
| General disorders | ||||
| Other | 20/109 (18.3%) | 20 | 17/249 (6.8%) | 17 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Respiratory | 25/109 (22.9%) | 25 | 51/249 (20.5%) | 51 |
Other (Not Including Serious) Adverse Events |
||||
| Lithium Carbonate | Historical Controls | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 99/109 (90.8%) | 175/249 (70.3%) | ||
| Cardiac disorders | ||||
| Cardiovascular | 1/109 (0.9%) | 46/249 (18.5%) | 63 | |
| Ear and labyrinth disorders | ||||
| Ears, Nose, Throat | 6/109 (5.5%) | 86/249 (34.5%) | 151 | |
| Endocrine disorders | ||||
| Endocrine/Metabolic | 4/109 (3.7%) | 8/249 (3.2%) | 8 | |
| Gastrointestinal disorders | ||||
| Gastrointestinal | 16/109 (14.7%) | 138/249 (55.4%) | 406 | |
| General disorders | ||||
| Other | 4/109 (3.7%) | 7/249 (2.8%) | 8 | |
| Musculoskeletal and connective tissue disorders | ||||
| Musculoskeletal | 6/109 (5.5%) | 85/249 (34.1%) | 170 | |
| Nervous system disorders | ||||
| Neurological | 27/109 (24.8%) | 98/249 (39.4%) | 209 | |
| Falls | 12/109 (11%) | 72/249 (28.9%) | 194 | |
| Psychiatric disorders | ||||
| Psychological | 4/109 (3.7%) | 56/249 (22.5%) | 83 | |
| Reproductive system and breast disorders | ||||
| Genitourinary | 2/109 (1.8%) | 64/249 (25.7%) | 109 | |
| Respiratory, thoracic and mediastinal disorders | ||||
| Respiratory | 12/109 (11%) | 76/249 (30.5%) | 123 | |
| Skin and subcutaneous tissue disorders | ||||
| Dermatological | 5/109 (4.6%) | 99/249 (39.8%) | 211 | |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT 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.
Results Point of Contact
| Name/Title | Giovanna Kushner |
|---|---|
| Organization | Forbes Norris MDA/ALS Center |
| Phone | 415-600-3983 |
| kushneg@cpmcri.org |
- 28.013