The purpose of this study is to assess the safety and tolerability of clenbuterol (taken by mouth) in subjects with ALS (amyotrophic lateral sclerosis) and to assess the effectiveness of clenbuterol with regard to motor function in subjects with ALS. Subjects will be in this study approximately 24 weeks. The study drug, clenbuterol, is taken twice a day. As part of this study subjects will have the following tests and procedures: medical history, vital signs, physical examination, blood tests, heart and lung function tests, muscle function test, ALSFRS-R (ALS Functional Rating Scale Revised), thyroid function and for women who can become pregnant, pregnancy tests.
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. In person visits will occur at weeks 0, 4, 12 and 24. Telephone visits will occur at weeks 1, 6, 16 and 20. During these visits several safety and efficacy outcome measures will be performed for research purposes including safety labs, thyroid functions, pregnancy testing, ALSFRS-R, FVC (forced vital capacity), and muscle strength testing (myometry). The critical test of treatment efficacy will be the comparison of the ALSFRS-R slope during treatment to the estimated pre-treatment slope. All participants will continue to have standard follow up care for their ALS at Duke (for patients followed here) or their local ALS clinic
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
25
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).
Duke University Medical center
Durham, North Carolina, United States
Number of Participants With Serious Adverse Events as Measured by Patient Reporting
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.
Time frame: Up to 24 weeks
Change in Motor Function Measured by ALSFRS-R
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.
Time frame: Baseline, week 4, week 12, week 16, week 20, and week 24
FVC Decline, Per-protocol Comparison
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.
Time frame: Baseline, week 4, week 12, and week 24
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