Asthma medicine slows ALS disease progression in small trial

Previous studies in patients, mice showed motor, strength gains with clenbuterol

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by Steve Bryson, PhD |

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Six months of treatment with clenbuterol, an asthma medication, slowed disease progression in adults with amyotrophic lateral sclerosis (ALS), according to data from a small U.S.-based Phase 2 clinical trial.

Despite these promising preliminary findings, more than half the participants withdrew from the study due to side effects.

“Nonetheless, this pilot trial provides valuable data for clenbuterol dosing, tolerability, and safety,” the researchers wrote, adding “a large-scale clinical trial is now warranted to determine its potential efficacy.”

The trial’s results were published in the Journal of Clinical Neuromuscular Disease in “Clenbuterol Treatment Is Safe and Associated With Slowed Disease Progression in a Small Open-Label Trial in Patients With Amyotrophic Lateral Sclerosis.”

Clenbuterol is an oral medication approved for treating asthma outside the U.S. It’s thought to have muscle strengthening and neuroprotective effects that could slow ALS, which is marked by progressive nerve damage and physical disability.

In a mouse model of ALS, clenbuterol was found to improve motor function and slow disease progression. Also, a previous pilot trial with 16 patients in Italy showed the therapy improved limb muscle strength and lung function, while stabilizing disability level.

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Clenbuterol’s effect on ALS disease progression

Building on these promising results, researchers at Duke University, in North Carolina, conducted a Phase 2 trial (NCT04245709) to test the safety and effectiveness of six months of treatment. They enrolled 25 adults diagnosed with possible, probable, or definite ALS between February 2020 and September 2020. Recruitment was temporarily paused due to the COVID-19 pandemic.

Participants had a mean age of 59 and 48% were women. They’d lived with the disease for a mean of 43 months (about 3.5 years), and 68% were taking the approved ALS therapy riluzole (sold as RilutekExservan, and Tiglutik).

All were started on 40 micrograms of clenbuterol a day. This was eventually increased to 80 micrograms twice a day.

Changes in various clinical measures were also assessed, including disease progression using the ALS Functional Rating Score (ALSFRS-R), lung function, and muscle strength. The ALSFRS-R scores range from 0 to 48, with lower scores indicating worse disability.

A total of 14 participants withdrew early, 13 due to side effects. The remaining patient discontinued due to concerns about traveling during the pandemic.

“Patients who discontinued the trial were significantly older and more likely to be male,” the researchers wrote.

The most commonly reported side effects included jitters, tremors, cramps, and insomnia, which were reported as the main reasons for withdrawing. There were no reports of treatment-related severe side effects or concerning laboratory or heart rhythm changes.

Results among patients who completed 24-week study

Among the 11 patients who completed the 24-week study, clenbuterol was associated with a slower disease progression, with a mean ALSFRS-R decline rate dropping from 0.56 to 0.17. One patient saw no progression over the six months, while four showed an increase in ALSFRS-R scores, indicating less disability.

The rates of ALSFRS-R decline for each person at the start were also significantly reduced after treatment with clenbuterol.

Ten of these patients had at least two measurements of lung function, as assessed by forced vital capacity (FVC), or the total amount of air that can be forcibly exhaled. The mean rate of FVC decline was slower after treatment (0.25 vs. 0.8), but this difference failed to reach statistical significance. Likewise, FVC rates for each person were not significantly different before and after treatment.

While more than half the participants didn’t complete treatment, 20 had at least one ALSFRS-R measurement after it started. Among them, 15 had a slower, but nonsignificant, ALSFRS-R decline rate with clenbuterol (0.33 vs. 0.52). Within-individual ALSFRS-R rate differences were also nonsignificant in this analysis.

Similarly, 16 of the initial 25 participants had at least two FVC measurements. Here, mean percent predicted FVC slope was significantly reduced after clenbuterol treatment (0.88 vs. 0.09). Within-individual FVC rates were also significantly different between before and after.

Muscle strength measurements of the lower and upper limbs were highly variable between patients before and after treatment. Most became weaker over six months, data suggested.

Despite these results, a few patients became significantly stronger over time, “which is unusual in the natural history of ALS,” the researchers wrote. “Our study confirms clenbuterol is safe for selected patients with ALS, but it was less tolerable at the doses we chose compared with an earlier Italian [trial], in which 16 patients were treated with 60 [micrograms] daily.”

A conclusion wasn’t able to be drawn about clenbuterol’s effectiveness because of the trial’s small population, large dropout rate, and lack of a placebo group,” said the researchers, who called for larger studies to clarify their results.