Testosterone supplementation combined with exercise program to improve muscle condition in men affected by inclusion body myositis.

This is a double-blinded, two-arm crossover RCT to test whether testosterone on a background of exercise training (see below) will improve measures of muscle strength and performance, and physical activity, in N=20 men with IBM, over 26 weeks (2 treatment-periods of 12 weeks separated by a 2 week wash-out period). The participants will be randomly assigned to a group receiving either testosterone or a placebo during the first treatment period, and then after washout, swapped to the alternate treatment during the second period.. Drugs applied Active name: testosterone Trade name: AndroForte 5, strength 5.0% w/v, dosage form 2 ml transdermal cream applied once daily by the patient over a 12-week period Placebo: The placebo contains exactly the same ingredients as the active (minus the testosterone). Inactive ingredients: cetomacrogol 1000, cetostearyl alcohol, carbopol 940, almond oil, dl-a-tocopheryl acetate (Vitamin E acetate), triethanolamine, Phenonip, butylated hydroxytoluene, anhydrous citric acid, purified water Trade name N/A, dosage form 2 ml transdermal cream applied once daily by the patient over a 12-week period The transdermal cream will be applied on an area of the torso with low subcutaneous fat, and then covered. Procedures: Medical assessments will be performed at IIID (Murdoch University) by Professor Needham or Professor Bu Yeap (Neurologist and Endocrinologist, respectively). Participants will be given the option to participate in a muscle biopsy sub-study to evaluate the effects of the intervention directly on the muscle. Muscle biopsies will be performed by Prof Phillipa Lamont (Neurologist) or Professor Needham at IIID. All these clinicians have at least 10 years experience. Exercise training: Exercise training will be a combination of light-moderate resistance training, balance training and aerobic exercise, tailored to each individual and supervised by investigators (with at least 10 years experience) from the School of Psychology and Exercise Science, Murdoch University. Exercise training will be tailored as follows: The progressive exercise program will be individually prescribed and progressed to accommodate the large variance in functional capabilities of each participant expected at baseline and in their individual exercise-response. This includes the specific exercises given (mode), the duration and frequency in which they are completed (depending on post-exercise pain and recovery scores) and the prescribed intensity of the exercise. Resistance exercise will largely be conducted using single joint exercises of the lower and upper limbs using elastic bands (Therabands); with varying levels of resistance providing the different intensities (different colour bands). Multi-joint compound exercises will be body-weight based. The initial exercise prescription will occur following baseline assessment. Progression of exercises and intensity will be based on RPE scores provided during fortnightly telephone calls and supervisory visits. The Home-based progressive exercise will comprise of resistance, aerobic/mobility, and balance exercises. All exercises will comprise of either resistance bands (therabands) or body weight movements. Resistance bands will largely be single-joint exercises while body weight movements will target whole body muscles involved in mobility and function however focus on extensors of knee and flexors of the wrist and fingers (i.e. leg extension, arm row, bicep curl). This will be supplemented with aerobic/mobility and functional exercises (i.e. walking, sitting and rising) and balance exercises (i.e. narrow stance, tandem stance). The duration of the exercise program will be approximately 30 minutes which will be completed three times a week and may progress to 45 minutes per session. The intensity of the exercise (moderate-light) will be determined using the RPE Borg scale. A rate of perceived exertion will be attained for every exercise prescribed for each participant and this information will be used to establish an appropriate intensity and regress or progress the exercise accordingly. The home-based exercise program will be completed only at home by participants for the intervention period. The program will be supervised via telephone and home visits. A one-off induction physical training session will be completed as part of the physical assessments at pre-intervention which will be conducted at the university. The participants will be asked to keep a record on a diary of their drug application, exercise and falls. Procedure timeline: (week 0 being when drug/placebo application begins and data collection starts) Medical assessments: week 0, 12, 26 Blood & urine collections: week 0, 12, 26 Muscle biopsies (optional): week -3, 12 Exercise and physical strength and performance assessments (under 2 hours): week 0, 12, 26 Exercise program (home based): daily Physical measures: daily and continuous (actigraph -over two 7 day-periods- / activity trackers -worn continuously-) DEXA scan: week 0, 12, 26 Location: - Medical assessment and examination: Institute for Immunology and Infectious Diseases (IIID), Murdoch University, Murdoch, Western Australia 6150 - Physical training and assessment: School of Psychology and Exercise Science, Murdoch University - Exercise program: home-based After completion of the initial 26 week phase of the study (completion of the 2 x 12 week treatment periods + 2 week wash-out), participants will be invited to join an Open Label Extension Study. This study aims to provide additional data on the safety and tolerability of testosterone in IBM, as well as tracking any changes in muscle strength during the extension study period. The established trial endpoints remain unchanged, with the addition of a secondary endpoint as follows: • Investigate safety and tolerability of transdermal testosterone in IBM over a 12 month period. This outcome will be measured by 3 monthly safety blood draws and 3 monthly medication dispensing visits, as well as review of compliance with medication administration and exercise via the medication/exercise diary and analysis of Fitbit data at 3 month intervals. Established endpoints will be measured at 6 month and 12 month timepoints. Visits at these timepoints will replicate Week 12 and Week 26 visits from the initial study phase. All patients who complete the initial phase of the study will be invited to take part in the extension study as soon as possible following their completion of the initial study phase. A detailed study schedule for the Open Label Extension Study is provided within the PICF for the Extension project. This extension has been considered as an amendment to the project by the Murdoch HREC and was granted approval on 29/03/2019.