Trial Outcomes & Findings for Clenbuterol on Motor Function in Individuals With Amyotrophic Lateral Sclerosis (NCT NCT04245709)
NCT ID: NCT04245709
Last Updated: 2022-09-06
Results Overview
The primary endpoint is safety of clenbuterol at 80 mcg BID. Adverse events and serious adverse events will be systematically gathered as the dose is increased.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
25 participants
Primary outcome timeframe
Up to 24 weeks
Results posted on
2022-09-06
Participant Flow
Participant milestones
| Measure |
Open Label Arm
This is an open label pilot trial in which 25 people with ALS will take clenbuterol orally at 40-80 micrograms twice daily for 24 weeks.
Clenbuterol: The intervention is treatment with oral clenbuterol at 40-80 micrograms twice daily for 24 weeks. Dosage will initially be 40 mcg daily for one week, then 40 mcg BID per oral daily for the next 5 weeks. If the 40 mcg BID per oral is well tolerated in the opinion of Dr. Bedlack, the dose will be increased to 80 mcg each morning/40 mcg each evening for one week, followed by 80 mcg BID per oral for the remainder of the study. The selected target dose (80 mcg BID) is based upon the experience with the long-term administration of clenbuterol, specifically the beneficial muscle effects in a Phase I/II clinical trial that enrolled patients with late-onset Pompe disease who were previously treated with enzyme replacement therapy (Koeberl et al. 2018).
|
|---|---|
|
Overall Study
STARTED
|
25
|
|
Overall Study
COMPLETED
|
11
|
|
Overall Study
NOT COMPLETED
|
14
|
Reasons for withdrawal
| Measure |
Open Label Arm
This is an open label pilot trial in which 25 people with ALS will take clenbuterol orally at 40-80 micrograms twice daily for 24 weeks.
Clenbuterol: The intervention is treatment with oral clenbuterol at 40-80 micrograms twice daily for 24 weeks. Dosage will initially be 40 mcg daily for one week, then 40 mcg BID per oral daily for the next 5 weeks. If the 40 mcg BID per oral is well tolerated in the opinion of Dr. Bedlack, the dose will be increased to 80 mcg each morning/40 mcg each evening for one week, followed by 80 mcg BID per oral for the remainder of the study. The selected target dose (80 mcg BID) is based upon the experience with the long-term administration of clenbuterol, specifically the beneficial muscle effects in a Phase I/II clinical trial that enrolled patients with late-onset Pompe disease who were previously treated with enzyme replacement therapy (Koeberl et al. 2018).
|
|---|---|
|
Overall Study
Adverse Event
|
13
|
|
Overall Study
Risk of travel during COVID19 pandemic
|
1
|
Baseline Characteristics
Clenbuterol on Motor Function in Individuals With Amyotrophic Lateral Sclerosis
Baseline characteristics by cohort
| Measure |
Open Label Arm
n=25 Participants
This is an open label pilot trial in which 25 people with ALS will take clenbuterol orally at 40-80 micrograms twice daily for 24 weeks.
Clenbuterol: The intervention is treatment with oral clenbuterol at 40-80 micrograms twice daily for 24 weeks. Dosage will initially be 40 mcg daily for one week, then 40 mcg BID per oral daily for the next 5 weeks. If the 40 mcg BID per oral is well tolerated in the opinion of Dr. Bedlack, the dose will be increased to 80 mcg each morning/40 mcg each evening for one week, followed by 80 mcg BID per oral for the remainder of the study. The selected target dose (80 mcg BID) is based upon the experience with the long-term administration of clenbuterol, specifically the beneficial muscle effects in a Phase I/II clinical trial that enrolled patients with late-onset Pompe disease who were previously treated with ERT (Koeberl et al. 2018).
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
18 Participants
n=99 Participants
|
|
Age, Categorical
>=65 years
|
7 Participants
n=99 Participants
|
|
Age, Continuous
|
59 years
n=99 Participants
|
|
Sex: Female, Male
Female
|
12 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
22 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=99 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
White
|
23 Participants
n=99 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=99 Participants
|
|
Region of Enrollment
United States
|
25 participants
n=99 Participants
|
PRIMARY outcome
Timeframe: Up to 24 weeksPopulation: Intention to treat analyses were performed for 20 participants who had at least one ALSFRS-R measurement post-treatment.
The primary endpoint is safety of clenbuterol at 80 mcg BID. Adverse events and serious adverse events will be systematically gathered as the dose is increased.
Outcome measures
| Measure |
Open Label Arm
n=20 Participants
This is an open label pilot trial in which 25 people with ALS will take clenbuterol orally at 40-80 micrograms twice daily for 24 weeks.
Clenbuterol: The intervention is treatment with oral clenbuterol at 40-80 micrograms twice daily for 24 weeks. Dosage will initially be 40 mcg daily for one week, then 40 mcg BID per oral daily for the next 5 weeks. If the 40 mcg BID per oral is well tolerated in the opinion of Dr. Bedlack, the dose will be increased to 80 mcg each morning/40 mcg each evening for one week, followed by 80 mcg BID per oral for the remainder of the study. The selected target dose (80 mcg BID) is based upon the experience with the long-term administration of clenbuterol, specifically the beneficial muscle effects in a Phase I/II clinical trial that enrolled patients with late-onset Pompe disease who were previously treated with ERT (Koeberl et al. 2018).
|
|---|---|
|
Number of Participants With Serious Adverse Events as Measured by Patient Reporting
|
2 Participants
|
SECONDARY outcome
Timeframe: Baseline, week 4, week 12, week 16, week 20, and week 24Population: Intention to treat analyses were performed for 20 participants who had at least one ALSFRS-R measurement post-treatment. These calculations for ALSFRS-R were based on the 11 patients who completed all 6 months on some dose of the drug, e.g. the per-protocol group.
The ALS Functional Rating Scale (ALSFRS-R) - 12 questions rated on a five-point scale, where 0= can't do, to 5= normal ability. It is utilized for monitoring the progression of disability in patients with ALS. The critical test for efficacy was comparison of the mean slope of the ALSFRS-R during treatment compared to pre-treatment. Pre-treatment slope for each participant was estimated as follows: (48-enrollment ALSFRS-R)/months since symptom onset. A statistically significant treatment effect was determined by a two-tailed, t-test, with a critical p value \< .05. Other analyses included a repeated measures ANOVA design (between and within subjects) of ALSFRS-R slopes before and during treatment.
Outcome measures
| Measure |
Open Label Arm
n=11 Participants
This is an open label pilot trial in which 25 people with ALS will take clenbuterol orally at 40-80 micrograms twice daily for 24 weeks.
Clenbuterol: The intervention is treatment with oral clenbuterol at 40-80 micrograms twice daily for 24 weeks. Dosage will initially be 40 mcg daily for one week, then 40 mcg BID per oral daily for the next 5 weeks. If the 40 mcg BID per oral is well tolerated in the opinion of Dr. Bedlack, the dose will be increased to 80 mcg each morning/40 mcg each evening for one week, followed by 80 mcg BID per oral for the remainder of the study. The selected target dose (80 mcg BID) is based upon the experience with the long-term administration of clenbuterol, specifically the beneficial muscle effects in a Phase I/II clinical trial that enrolled patients with late-onset Pompe disease who were previously treated with ERT (Koeberl et al. 2018).
|
|---|---|
|
Change in Motor Function Measured by ALSFRS-R
|
-0.17 slope
Standard Deviation 0.25
|
SECONDARY outcome
Timeframe: Baseline, week 4, week 12, and week 24Population: For the 11 patients who completed all 6 months on some dose of the drug, there were 10 who had at least two FVC measurements. Seven patients had a baseline FVC measurement which was used to calculate the pre-treatment slope estimate, for the 3 patients without a baseline measurement, imputation of the baseline FVC was performed using all data available for each patient.
Comparison of the mean slope of percent predicted FVC during treatment versus pre-treatment. Pre-treatment slope for each participant was estimated as follows: (100%-enrollment percent predicted FVC)/months since symptom onset.
Outcome measures
| Measure |
Open Label Arm
n=10 Participants
This is an open label pilot trial in which 25 people with ALS will take clenbuterol orally at 40-80 micrograms twice daily for 24 weeks.
Clenbuterol: The intervention is treatment with oral clenbuterol at 40-80 micrograms twice daily for 24 weeks. Dosage will initially be 40 mcg daily for one week, then 40 mcg BID per oral daily for the next 5 weeks. If the 40 mcg BID per oral is well tolerated in the opinion of Dr. Bedlack, the dose will be increased to 80 mcg each morning/40 mcg each evening for one week, followed by 80 mcg BID per oral for the remainder of the study. The selected target dose (80 mcg BID) is based upon the experience with the long-term administration of clenbuterol, specifically the beneficial muscle effects in a Phase I/II clinical trial that enrolled patients with late-onset Pompe disease who were previously treated with ERT (Koeberl et al. 2018).
|
|---|---|
|
FVC Decline, Per-protocol Comparison
|
-0.25 slope
Standard Deviation 0.85
|
Adverse Events
Open Label Arm
Serious events: 2 serious events
Other events: 25 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Open Label Arm
n=25 participants at risk
This is an open label pilot trial in which 25 people with ALS will take clenbuterol orally at 40-80 micrograms twice daily for 24 weeks.
Clenbuterol: The intervention is treatment with oral clenbuterol at 40-80 micrograms twice daily for 24 weeks. Dosage will initially be 40 mcg daily for one week, then 40 mcg BID per oral daily for the next 5 weeks. If the 40 mcg BID per oral is well tolerated in the opinion of Dr. Bedlack, the dose will be increased to 80 mcg each morning/40 mcg each evening for one week, followed by 80 mcg BID per oral for the remainder of the study. The selected target dose (80 mcg BID) is based upon the experience with the long-term administration of clenbuterol, specifically the beneficial muscle effects in a Phase I/II clinical trial that enrolled patients with late-onset Pompe disease who were previously treated with ERT (Koeberl et al. 2018).
|
|---|---|
|
Injury, poisoning and procedural complications
Near-drowning accident
|
4.0%
1/25 • Number of events 1 • 24 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary emboli
|
4.0%
1/25 • Number of events 1 • 24 weeks
|
Other adverse events
| Measure |
Open Label Arm
n=25 participants at risk
This is an open label pilot trial in which 25 people with ALS will take clenbuterol orally at 40-80 micrograms twice daily for 24 weeks.
Clenbuterol: The intervention is treatment with oral clenbuterol at 40-80 micrograms twice daily for 24 weeks. Dosage will initially be 40 mcg daily for one week, then 40 mcg BID per oral daily for the next 5 weeks. If the 40 mcg BID per oral is well tolerated in the opinion of Dr. Bedlack, the dose will be increased to 80 mcg each morning/40 mcg each evening for one week, followed by 80 mcg BID per oral for the remainder of the study. The selected target dose (80 mcg BID) is based upon the experience with the long-term administration of clenbuterol, specifically the beneficial muscle effects in a Phase I/II clinical trial that enrolled patients with late-onset Pompe disease who were previously treated with ERT (Koeberl et al. 2018).
|
|---|---|
|
Nervous system disorders
Jitters/tremors
|
40.0%
10/25 • Number of events 10 • 24 weeks
|
|
General disorders
Insomnia
|
28.0%
7/25 • Number of events 7 • 24 weeks
|
|
Musculoskeletal and connective tissue disorders
Cramps/spasms
|
32.0%
8/25 • Number of events 8 • 24 weeks
|
|
Nervous system disorders
Stiffness/spasticity
|
24.0%
6/25 • Number of events 6 • 24 weeks
|
|
Hepatobiliary disorders
Elevated liver transaminases
|
12.0%
3/25 • Number of events 3 • 24 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Increased work of breathing
|
8.0%
2/25 • Number of events 2 • 24 weeks
|
|
General disorders
Decreased appetite/weight loss
|
8.0%
2/25 • Number of events 2 • 24 weeks
|
|
Gastrointestinal disorders
GI upset/nausea
|
8.0%
2/25 • Number of events 2 • 24 weeks
|
|
Nervous system disorders
Headache
|
4.0%
1/25 • Number of events 1 • 24 weeks
|
|
Cardiac disorders
Palpitations
|
4.0%
1/25 • Number of events 1 • 24 weeks
|
|
Musculoskeletal and connective tissue disorders
Elevated creatine kinase (CK)
|
4.0%
1/25 • Number of events 1 • 24 weeks
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
4.0%
1/25 • Number of events 1 • 24 weeks
|
|
Renal and urinary disorders
Elevated PSA
|
4.0%
1/25 • Number of events 1 • 24 weeks
|
|
General disorders
Tooth removal
|
4.0%
1/25 • Number of events 1 • 24 weeks
|
|
Skin and subcutaneous tissue disorders
Pruritis
|
4.0%
1/25 • Number of events 1 • 24 weeks
|
|
Musculoskeletal and connective tissue disorders
Foot pain
|
4.0%
1/25 • Number of events 1 • 24 weeks
|
|
Nervous system disorders
Restless legs
|
4.0%
1/25 • Number of events 1 • 24 weeks
|
|
Musculoskeletal and connective tissue disorders
Tendinitis
|
4.0%
1/25 • Number of events 1 • 24 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
4.0%
1/25 • Number of events 1 • 24 weeks
|
|
General disorders
Hot flashes
|
4.0%
1/25 • Number of events 1 • 24 weeks
|
|
Nervous system disorders
Dizziness/instability
|
4.0%
1/25 • Number of events 1 • 24 weeks
|
|
Nervous system disorders
Increased fasciculations
|
4.0%
1/25 • Number of events 1 • 24 weeks
|
|
Psychiatric disorders
Anxiety
|
4.0%
1/25 • Number of events 1 • 24 weeks
|
|
Cardiac disorders
ECG changes
|
4.0%
1/25 • Number of events 1 • 24 weeks
|
|
Endocrine disorders
Elevated thyroxine (T4)
|
4.0%
1/25 • Number of events 1 • 24 weeks
|
|
Cardiac disorders
Tachycardia
|
4.0%
1/25 • Number of events 1 • 24 weeks
|
|
Gastrointestinal disorders
Constipation
|
4.0%
1/25 • Number of events 1 • 24 weeks
|
|
Renal and urinary disorders
Urinary tract infection
|
4.0%
1/25 • Number of events 1 • 24 weeks
|
|
Nervous system disorders
Accelerated disease progression
|
4.0%
1/25 • Number of events 1 • 24 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place