Facioscapulohumeral muscular dystrophy (FSHD) is the second most common adult muscular dystrophy in the world with a global prevalence of ~4:100,000. Clinically, patients with FSHD experience progressive weakness, muscle wasting, fatigue, and respiratory decline. As adult patients with FSHD age, they frequently develop difficulty walking or lose the ability to ambulate due to profound weakness and muscle atrophy. Currently, there are no therapies that have been demonstrated to reverse or even slow the progressive symptoms associated with FSHD. Large scale clinical trials have found that testosterone combined with recombinant human growth hormone (rHGH) (combination therapy) is well tolerated and effective in synergistically improving respiratory function, lean body mass, protein synthesis, strength, and aerobic endurance in healthy adult human populations. Both testosterone and rHGH are readily available and approved for human use but have never been formally studied together in a muscular dystrophy population. We propose a 36-week, proof-of-concept clinical study of the safety and tolerability of daily rHGH combined with biweekly testosterone injections in men with FSHD. All participants will be serially and closely monitored during a 24 week period of combination therapy followed by a 12 week washout period. Safety assessments will include monitoring for medication side effects, laboratory abnormalities, physical exam changes, and EKG alterations. As a secondary objective, we will examine the pharmacokinetic effects of combination therapy on lean body mass and serum biomarkers. Participants will also have serial assessments of their ambulation, strength, physical function, patient-reported disease burden, and respiratory function. Ultimately, this study will generate extensive data regarding the clinical safety, pharmacokinetics, and change in body composition and clinical function associated with combination therapy in a predefined FSHD population.

Public Health Relevance

Facioscapulohumeral muscular dystrophy (FSHD) is a progressive hereditary disorder that affects ~4 per 100,000 of the world's population. Severe weakness, muscle wasting, and impaired ambulation are common in FSHD. In this clinical study, we will evaluate the safety, tolerability, and effects of testosterone paired with recombinant human growth hormone (rHGH) on lean body mass, serum markers, and physical function in patients with FSHD.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS095813-04
Application #
9919651
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Program Officer
Conwit, Robin
Project Start
2017-08-01
Project End
2021-04-30
Budget Start
2020-05-01
Budget End
2021-04-30
Support Year
4
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Rochester
Department
Neurology
Type
School of Medicine & Dentistry
DUNS #
041294109
City
Rochester
State
NY
Country
United States
Zip Code
14627