Abstract
Background. Inclusion body myositis (IBM) is the most common acquired skeletal muscle disease associated with ageing and involves both an autoimmune attack on muscle fibres as well as muscle degeneration with protein deposition. There have been multiple studies showing a relationship between exercise and improved outcomes in IBM, however only one prior trial showed a modest benefit of Oxandrolone in IBM. No studies have explored a combination of the two. We hypothesised that a combination of exercise training and testosterone treatment would improve muscle strength and physical activity in males affected by IBM, more than exercise alone.
Methods. This pilot study adopted a double-blinded, placebo-controlled, crossover design to assess whether testosterone combined with a prescribed exercise program would improve measures of muscle strength, physical activity and quality of life in men affected by IBM, over exercise alone. Treatment (exercise and placebo) and placebo (exercise only) arms were 12 weeks in duration, with a two-week wash-out period between arms. Primary outcome was quadriceps strength, measured by isokinetic dynamometer (Humac Norm). Secondary outcomes included lean body mass, functional tests and Patient Reported Outcomes (PROs). Outcome measures were collected at baseline, Week 12 and Week 26. In response to participant feedback, a 12-month Open Label Extension (OLE) was offered, with outcome measures collected at new baseline, 6-months and 12-months.
Results. The primary outcome, quadriceps extension strength the placebo and treatment arms, was non-significant. The DEXA assessment of lean body mass and other functional tests were also non-significant between the placebo and treatment arms. There was a significant reduction of peak torque extension at 60 degrees during the placebo period (p=0.04). Within the SF-36 questionnaire, the domain of ‘role limitations due to emotional problems’ demonstrated higher scores during the testosterone arm when compared to the placebo arm (p=0.044). All other domains, as well as the IBM-FRS, were non-significant. Within the OLE, the 2- minute walk test regular and fast were significant at 6 months (p=0.03 and p=0.032 respectively) but not at 12 months. The most common adverse event reported was falls which were considered a complication of IBM rather than the study. Within the OLE, 3 of the 12 participants withdrew from the study due to adverse events related to rising prostate specific antigen and haematocrit.
Conclusions. In this study comparing exercise alone to exercise in combination of testosterone supplementation, we were unable to detect a significant effect of the treatment on muscle strength, function or quality of life. However, peak torque extension at 60 degrees worsened significantly during the exercise-only arm, which could indicate that testosterone conferred some stabilisation effect during the treatment period. Individuals on testosterone also felt that their daily activities were not as limited due to the emotional problems compared with placebo, perhaps indicating that testosterone contributes to improved mood and mental health. Individuals who participated in the OLE had improved walk tests at 6 months which then declined at 12 months. This warrants further investigation in future studies, where the benefit of testosterone on walking strength may decline after a prolonged period. Finally, we note that 12 men requested the OLE due to perceived positive effects and lack of adverse effects, so potentially the benefits of testosterone require a longer period of intervention to manifest than that applied during the crossover phase.