A 20-person, open-label pilot trial conducted in Italy and designed to test the safety, tolerability and efficacy of clenbuterol in people with spinal-bulbar muscular atrophy (SBMA, or Kennedy disease) found that the drug was well-tolerated, although some possible safety issues were identified. Trial investigators note that the study findings suggest a possible “positive effect on SBMA disease progression.”
Clenbuterol, which belongs to a class of drugs called beta 2 agonists, opens airways, increases heart rate and has a general stimulating effect on the nervous system. Some studies have suggested that these drugs can have a muscle-building (anabolic) effect, although the mechanism is not clear.
Although approved in some countries for treatment of asthma or other breathing disorders, clenbuterol is not approved by the U.S. Food and Drug Administration (FDA) to treat human conditions or diseases in the United States.
The researchers say that further studies in mouse models of SBMA may help determine the mechanism by which clenbuterol appears to have led to functional improvements in people with SBMA in this pilot trial. They also suggest that additional clinical trials in people with SBMA to test the therapeutic potential of clenbuterol or similar beta 2 agonist drugs may be warranted.
The team published its findings online May 3, 2013, in Neurology. To read the full report, for a fee, see: Pilot Trial of Clenbuterol in Spinal and Bulbar Muscular Atrophy.
Twenty people with genetically confirmed SBMA, ages 41 to 75 years old and able to walk independently or with the use of a cane, participated in the trial. Each underwent a detailed medical history, physical examination with laboratory tests, and a full cardiac (heart) evaluation at the beginning of the study (“baseline”).
All participants received one tablet (0.02 milligrams) of clenbuterol daily for two days, after which the dose was increased to one tablet twice a day (for a total of 0.04 milligrams) for 12 months.
Tests to assess safety, muscle function and respiratory function were conducted at follow-up visits after three, six, nine and 12 months. These included:
Clinical examinations that included heart rate and blood pressure checks, in addition to other tests to examine heart health, also were administered to monitor for heart-related side effects.
Sixteen participants completed the study. (Two withdrew after three months due to hand tremors; one due to the need for surgery; and one because of poor compliance.)
In those who completed the study, clenbuterol was generally well-tolerated. The most common side effects were hand tremors (in nine participants) and muscle cramps (in three participants). These occurred mainly early in the treatment and decreased over time.
A concern was that during clenbuterol treatment, blood levels of the creatine kinase enzyme increased by an average of 46 percent compared to baseline values. Creatine kinase leaks out of damaged muscle fibers and is considered a rough indicator of ongoing muscle injury.
Trial investigators reported a significant 12.7 percent average increase in the distance participants walked in six minutes after three months of treatment, an increase that persisted through 12 months. The investigators say these results are "particularly intriguing" because the natural history of SBMA is characterized by an 11.3 percent decrease per year in the distance walked in six minutes.
There also was a significant improvement (19.4 percent increase) in participants’ average FVC scores after three months of treatment. As with the six-minute-walk scores, improved FVC scores also persisted through 12 months.
Despite the improvements seen in the six-minute-walk test and FVC assessment, data showed no differences in muscle strength or function as assessed using the MRC and ALSFRS-R, between the baseline exam and each follow-up visit.
Trial investigators note that future studies in animal models will be needed to help determine the mechanism by which clenbuterol may have acted to cause the apparent improvement in walking distance and respiratory capacity, and to investigate the reason for the increase in creatine kinase levels.
In addition, they say, further trials to test the drug’s therapeutic potential may be warranted.
"The positive result of this small pilot study is encouraging for the development of a treatment for SBMA," said MDA Vice President of Research Jane Larkindale. "However, researchers will need to look carefully at this data to design new studies to determine why increased creatine kinase was observed, as long-term muscle damage may prevent this compound’s use. Other related compounds also should be considered for testing."