Testosterone treatment combined with exercise to improve muscle strength, physical function and quality of life in men affected by inclusion body myositis: A randomised, double-blind, placebo-controlled, crossover trial

Abstract

Introduction Inclusion body myositis (IBM) is the most commonly acquired skeletal muscle disease of older adults involving both autoimmune attack and muscle degeneration. As exercise training can improve outcomes in IBM, this study assessed whether a combination of testosterone supplementation and exercise training would improve muscle strength, physical function and quality of life in men affected by IBM, more than exercise alone. Methods This pilot study was a single site randomised, double-blind, placebo-controlled, crossover study. Testosterone (exercise and testosterone cream) and placebo (exercise and placebo cream) were each delivered for 12 weeks, with a two-week wash-out between the two periods. The primary outcome measure was improvement in quadriceps isokinetic muscle strength. Secondary outcomes included assessment of isokinetic peak flexion force, walk capacity and patient reported outcomes, and other tests, comparing results between the placebo and testosterone arms. A 12-month Open Label Extension (OLE) was offered using the same outcome measures collected at 6 and 12-months. Results 14 men completed the trial. There were no significant improvements in quadriceps extension strength or lean body mass, nor any of the secondary outcomes. Improvement in the RAND Short Form 36 patient reported outcome questionnaire ‘emotional wellbeing’ sub-category was reported during the testosterone arm compared to the placebo arm (mean difference [95% CI]: 6.0 points, [95% CI 1.7,10.3]). The OLE demonstrated relative disease stability over the 12-month period but with a higher number of testosterone-related adverse events. Conclusions Adding testosterone supplementation to exercise training did not significantly improve muscle strength or physical function over a 12-week intervention period, compared to exercise alone. However, the combination improved emotional well-being over this period, and relative stabilisation of disease was found during the 12-month OLE. A longer duration trial involving a larger group of participants is warranted.

Effectiveness of conservative non-pharmacological interventions in people with muscular dystrophies: a systematic review and meta-analysis

“…Furthermore, while this review and meta-analysis did not include studies combining conservative non-pharmacological treatments with pharmacological interventions, preventing a direct comparison of their effectiveness, previous research in MD and NMD suggests that conservative non-pharmacological interventions have comparable, if not superior, effectiveness than pharmacological treatments. 60 61 For instance, very large, although non-significant, ESs (range: 1.46–8.93) strongly favoured conservative interventions over pharmacological treatments in specific outcomes (e.g. Berg balance, grip strength, 2-min walk test, physical functioning, role limitations due to physical health and emotional problems) in the study by Connor et al .…”

“…60 61 For instance, very large, although non-significant, ESs (range: 1.46-8.93) strongly favoured conservative interventions over pharmacological treatments in specific outcomes (e.g. Berg balance, grip strength, 2-min walk test, physical functioning, role limitations due to physical health and emotional problems) in the study by Connor et al 60 Numerous questions regarding the effectiveness of these interventions remain unanswered, specifically about certain outcomes, populations and intervention types. Pain, a common and distressing symptom in MD, 62 63 offers anecdotal indications of potential relief through non-pharmacological interventions such as hydrotherapy.…”

“…Berg balance, grip strength, 2-min walk test, physical functioning, role limitations due to physical health and emotional problems) in the study by Connor et al . 60 …”

Sporadic Inclusion Body Myositis at the Crossroads between Muscle Degeneration, Inflammation, and Aging

“…Besides pharmacological agents, different exercise regimens have been assessed as possible therapeutic approaches for sIBM [ 248 , 249 , 250 , 251 , 252 , 253 ]. These studies eliminated the concern of exercise being potentially harmful and demonstrated that physical activity ameliorates strength in sIBM patients.…”

Idiopathic inflammatory myopathies: one year in review 2023

“…Non-pharmacological treatment includes physical therapy of the affected muscles to prevent disuse atrophy. A single site randomised, double-blind, placebo-controlled, crossover study assessed whether a combination of testosterone supplementation and exercise training would improve muscle strength, physical function and quality of life in men affected by IBM, more than exercise alone (103). Exercise and transdermal testosterone and placebo (exercise and placebo cream) were each delivered for 12 weeks, with a two-week wash-out between the two periods.…”