Trial Outcomes & Findings for A Multi-Center Controlled Screening Trial of Safety and Efficacy of Lithium Carbonate in Subjects With Amyotrophic Lateral Sclerosis (ALS) (NCT NCT00790582)

Last Updated: 2020-10-30

Results Overview

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)

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

109 participants

Primary outcome timeframe

Baseline, Month 1,3,4.5,6,7.5,9,10.5,12,13

Results posted on

2020-10-30

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	Treatment 109 subjects were assigned to treatment with lithium carbonate	Control 249 placebo subjects from previous clinical trials
Overall Study STARTED	109	249
Overall Study COMPLETED	78	162
Overall Study NOT COMPLETED	31	87

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment 109 subjects were assigned to treatment with lithium carbonate	Control 249 placebo subjects from previous clinical trials
Overall Study Death	14	32
Overall Study Physician Decision	7	1
Overall Study Lost to Follow-up	3	3
Overall Study Withdrawal by Subject	7	51

Baseline Characteristics

A Multi-Center Controlled Screening Trial of Safety and Efficacy of Lithium Carbonate in Subjects With Amyotrophic Lateral Sclerosis (ALS)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lithium Carbonate n=109 Participants	Historical Controls n=249 Participants	Total n=358 Participants Total of all reporting groups
Age, Continuous	56.2 years STANDARD_DEVIATION 11.7 • n=5 Participants	57.6 years STANDARD_DEVIATION 11.0 • n=7 Participants	57.2 years STANDARD_DEVIATION 11.2 • n=5 Participants
Age, Customized <=18 years	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Age, Customized Between 18 and 65 years	84 participants n=5 Participants	186 participants n=7 Participants	270 participants n=5 Participants
Age, Customized >=65 years	25 participants n=5 Participants	63 participants n=7 Participants	88 participants n=5 Participants
Age, Customized 18 to 75 years	109 participants n=5 Participants	249 participants n=7 Participants	358 participants n=5 Participants
Sex: Female, Male Female	38 Participants n=5 Participants	83 Participants n=7 Participants	121 Participants n=5 Participants
Sex: Female, Male Male	71 Participants n=5 Participants	166 Participants n=7 Participants	237 Participants n=5 Participants
Region of Enrollment United States	109 participants n=5 Participants	249 participants n=7 Participants	358 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Month 1,3,4.5,6,7.5,9,10.5,12,13

Outcome measures

Outcome measures
Measure	Lithium Carbonate n=109 Participants	Historical Controls n=249 Participants
Change in Monthly Rate of Decline in ALSFRS-R (Amyotrophic Lateral Sclerosis Functional Rating Score - Revised)	1.20 points per month Interval 1.04 to 1.35	1.01 points per month Interval 0.9 to 1.11

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Lithium Carbonate n=109 Participants	Historical Controls n=249 Participants
Vital Capacity	2.84 Decline in the percent predicted/month Interval 2.36 to 3.32	2.91 Decline in the percent predicted/month Interval 2.59 to 3.23

Adverse Events

Lithium Carbonate

Serious events: 62 serious events

Other events: 99 other events

Deaths: 14 deaths

Historical Controls

Serious events: 91 serious events

Other events: 175 other events

Deaths: 44 deaths

Serious adverse events

Serious adverse events
Measure	Lithium Carbonate n=109 participants at risk Treated Patients	Historical Controls n=249 participants at risk Placebo Patients
Respiratory, thoracic and mediastinal disorders Respiratory	22.9% 25/109 • Number of events 25 • Adverse events were recorded for the duration of the trial (1 year).	20.5% 51/249 • Number of events 51 • Adverse events were recorded for the duration of the trial (1 year).
Gastrointestinal disorders Gastrointestinal	15.6% 17/109 • Number of events 17 • Adverse events were recorded for the duration of the trial (1 year).	9.2% 23/249 • Number of events 23 • Adverse events were recorded for the duration of the trial (1 year).
General disorders Other	18.3% 20/109 • Number of events 20 • Adverse events were recorded for the duration of the trial (1 year).	6.8% 17/249 • Number of events 17 • Adverse events were recorded for the duration of the trial (1 year).

Other adverse events

Other adverse events
Measure	Lithium Carbonate n=109 participants at risk Treated Patients	Historical Controls n=249 participants at risk Placebo Patients
Gastrointestinal disorders Gastrointestinal	14.7% 16/109 • Adverse events were recorded for the duration of the trial (1 year).	55.4% 138/249 • Number of events 406 • Adverse events were recorded for the duration of the trial (1 year).
Cardiac disorders Cardiovascular	0.92% 1/109 • Adverse events were recorded for the duration of the trial (1 year).	18.5% 46/249 • Number of events 63 • Adverse events were recorded for the duration of the trial (1 year).
Skin and subcutaneous tissue disorders Dermatological	4.6% 5/109 • Adverse events were recorded for the duration of the trial (1 year).	39.8% 99/249 • Number of events 211 • Adverse events were recorded for the duration of the trial (1 year).
Ear and labyrinth disorders Ears, Nose, Throat	5.5% 6/109 • Adverse events were recorded for the duration of the trial (1 year).	34.5% 86/249 • Number of events 151 • Adverse events were recorded for the duration of the trial (1 year).
Endocrine disorders Endocrine/Metabolic	3.7% 4/109 • Adverse events were recorded for the duration of the trial (1 year).	3.2% 8/249 • Number of events 8 • Adverse events were recorded for the duration of the trial (1 year).
Reproductive system and breast disorders Genitourinary	1.8% 2/109 • Adverse events were recorded for the duration of the trial (1 year).	25.7% 64/249 • Number of events 109 • Adverse events were recorded for the duration of the trial (1 year).
Musculoskeletal and connective tissue disorders Musculoskeletal	5.5% 6/109 • Adverse events were recorded for the duration of the trial (1 year).	34.1% 85/249 • Number of events 170 • Adverse events were recorded for the duration of the trial (1 year).
Nervous system disorders Neurological	24.8% 27/109 • Adverse events were recorded for the duration of the trial (1 year).	39.4% 98/249 • Number of events 209 • Adverse events were recorded for the duration of the trial (1 year).
General disorders Other	3.7% 4/109 • Adverse events were recorded for the duration of the trial (1 year).	2.8% 7/249 • Number of events 8 • Adverse events were recorded for the duration of the trial (1 year).
Nervous system disorders Falls	11.0% 12/109 • Adverse events were recorded for the duration of the trial (1 year).	28.9% 72/249 • Number of events 194 • Adverse events were recorded for the duration of the trial (1 year).
Psychiatric disorders Psychological	3.7% 4/109 • Adverse events were recorded for the duration of the trial (1 year).	22.5% 56/249 • Number of events 83 • Adverse events were recorded for the duration of the trial (1 year).
Respiratory, thoracic and mediastinal disorders Respiratory	11.0% 12/109 • Adverse events were recorded for the duration of the trial (1 year).	30.5% 76/249 • Number of events 123 • Adverse events were recorded for the duration of the trial (1 year).

Additional Information

Giovanna Kushner

Forbes Norris MDA/ALS Center

Phone: 415-600-3983

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place