Amyotrophic Lateral Sclerosis
Conditions
Keywords
ALS, Amyotrophic Lateral Sclerosis, Lou Gehrig's Disease, Lithium, Lithium Carbonate
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.
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.
Interventions
DRUGlithium carbonate
The dosage of lithium carbonate will be adjusted for each individual. The maximum dose is 450mg/day.
Sponsors
Muscular Dystrophy Association
Forbes Norris MDA/ALS Research Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
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 details
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.
Participants by arm
| Arm | Count |
|---|---|
| Lithium Carbonate | 109 |
| Historical Controls | 249 |
| Total | 358 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 14 | 32 |
| Overall Study | Lost to Follow-up | 3 | 3 |
| Overall Study | Physician Decision | 7 | 1 |
| Overall Study | Withdrawal by Subject | 7 | 51 |
Baseline characteristics
| Characteristic | Lithium Carbonate | Historical Controls | Total |
|---|---|---|---|
| Age, Continuous | 56.2 years STANDARD_DEVIATION 11.7 | 57.6 years STANDARD_DEVIATION 11 | 57.2 years STANDARD_DEVIATION 11.2 |
| Age, Customized 18 to 75 years | 109 participants | 249 participants | 358 participants |
| Age, Customized <=18 years | 0 participants | 0 participants | 0 participants |
| Age, Customized >=65 years | 25 participants | 63 participants | 88 participants |
| Age, Customized Between 18 and 65 years | 84 participants | 186 participants | 270 participants |
| Region of Enrollment United States | 109 participants | 249 participants | 358 participants |
| Sex: Female, Male Female | 38 Participants | 83 Participants | 121 Participants |
| Sex: Female, Male Male | 71 Participants | 166 Participants | 237 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 14 / 109 | 44 / 249 |
| other Total, other adverse events | 99 / 109 | 175 / 249 |
| serious Total, serious adverse events | 62 / 109 | 91 / 249 |
Outcome results
Primary
Change in Monthly Rate of Decline in ALSFRS-R (Amyotrophic Lateral Sclerosis Functional Rating Score - Revised)
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
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Lithium Carbonate | Change in Monthly Rate of Decline in ALSFRS-R (Amyotrophic Lateral Sclerosis Functional Rating Score - Revised) | 1.20 points per month |
| Historical Controls | Change in Monthly Rate of Decline in ALSFRS-R (Amyotrophic Lateral Sclerosis Functional Rating Score - Revised) | 1.01 points per month |
Secondary
Vital Capacity
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
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Lithium Carbonate | Vital Capacity | 2.84 Decline in the percent predicted/month |
| Historical Controls | Vital Capacity | 2.91 Decline in the percent predicted/month |