Body Composition Changes With Albuterol and Caffeine Versus Placebo in Adolescents

Previous studies done at Pennington Biomedical have demonstrated that the equivalent of oral
albuterol 4mg three times a day (tid) with oral caffeine 100mg tid reduces body fat and
increases lean tissue in rodents more than the addition of the effect of the two components
separately. The combination of albuterol with caffeine changed body composition without
changing food intake. An adult male taking albuterol 4 mg orally tid plus caffeine 100mg
orally tid increased lean mass by 1.25% and decreased fat mass by 1.2% over a two month
period. These effects are expected to be even greater in a growing adolescent. This pilot
project will take the first step towards trying to understanding the safety and potential
efficacy of this drug combination. The prospect of using inexpensive medications already
approved in the pediatric population for the treatment of asthma as a novel treatment for
adolescent obesity addresses a medical need that is presently unmet.

Food restriction in adolescence is not only difficult to accomplish, but it also raises
concerns about growth and development. A medication approved for the treatment of obesity in
the adolescent age group that improves body composition by reducing body fat and increasing
lean tissue without needing to restrict food intake would be a useful tool for physicians who
address the treatment of obesity in adolescents. Albuterol is a medication, approved for ages
6 and older, used for the treatment of asthma and has also been shown to increase muscle
strength and lean body mass in children with spinal muscular atrophy and in healthy young men
during an exercise training program. A drug approved for the treatment of adolescent obesity
that increases lean tissue, decreases fat tissue and can be given in conjunction with
lifestyle modifications would be welcomed by both pediatricians who treat these adolescents
and by adolescents who are stigmatized by their obesity.

A provisional patent has been submitted by Pennington Biomedical Research Center to protect
the combination of caffeine and albuterol in a 1:25 ratio for synergistically increasing
muscle mass and decreasing fat mass as a potential treatment for obesity in adolescents.

This study will be a double-blinded, randomized, placebo-controlled, pilot study in which
subjects will be randomized to receive either placebo or a combination of Albuterol 4 mg and
Caffeine 100mg three times per day orally for a total of 8 weeks. Each subject will continue
on the study intervention for the entire duration of treatment

Inclusion Criteria:

- Healthy males or females with a BMI ≥ 95th percentile

- Between 12 and 17 years of age inclusive

- Tanner Stage III and above

Exclusion Criteria:

- Weigh less than 50 kg

- Have a family history of sudden death or hypertrophic cardiomyopathy

- Have a history of unexplained syncope

- Have a marked baseline prolongation of QT/QTc interval (QTc interval >450 ms), a
history of additional risk factors for torsade de pointes (e.g., heart failure,
hypokalemia, family history of Long QT Syndrome), or use concomitant medications that
prolong the QT/QTc interval

- Have history of asthma, hypertension, thyroid disease, or significant neurologic
disease such as seizure disorder

- Are pregnant, planning to become pregnant, or nursing. Females who are sexually active
must be using adequate contraception.

- Take a medication known to affect weight or body composition like systemic
glucocorticoids, atypical anti-psychotics, or weight loss medications

- Take beta-stimulators or beta-blockers on a regular basis

- Take stimulants for attention deficit disorder

- Take monoamine oxidase inhibitors, tricyclic antidepressants, or diuretics

- Take any chronic medication that has not had a stable dose for 1 month or longer

- Have type 1 or type 2 diabetes

- Have any significant cardiac disease (such as heart failure, arrhythmias, or valve
disease), uncontrolled pulmonary disease, chronic liver disease, chronic kidney
disease, or chronic infectious disease

- Have any significant psychiatric illness that is unstable or untreated such as bipolar
disorder, severe depression, or severe anxiety

- Have a history of suicidal ideation

- Have an allergy or hypersensitivity to albuterol

- Are unwilling to discontinue caffeine-containing products while in the study

- Are deemed unfit to participate in the study based on evaluation by the medical
investigator