Recombinant human growth hormone (rHGH) for muscle enhancement in knee osteoarthritis: protocol for a pilot, randomised placebo-controlled trial

Introduction The management of active patients with symptomatic knee osteoarthritis (KnOA) who are too young for total knee arthroplasty poses a specific challenge to clinicians. Research studies show that improving quadriceps muscle strength improves pain and function; however, aspects of the disease render it difficult for patients to achieve and maintain improvements. Recombinant human growth hormone (rHGH) is shown to increase the magnitude and duration of muscle growth when combined with exercise treatment in adult populations. Hence, rHGH combined with physical therapy may provide meaningful benefits in the treatment of KnOA. Methods and analysis This is a single-centre, double-blind, randomised trial to pilot a future Phase III trial from 2025 to 2028. Participants are aged 18–60 with clinical and radiographic evidence of isolated degenerative arthritis of the knee (patellofemoral or tibiofemoral). The investigational product is rHGH (Saizen (somatropin of rDNA origin, EMD Serono)) and a saline placebo. Participants will deliver the solution via subcutaneous injection area once per day at a dose of 0.5 mg HGH per body surface area (0.5 mg/m 2 ) for 6 weeks, alongside participation in a lower limb strengthening programme developed by rehabilitation specialists. 17 participants will be recruited into each study arm. The primary outcomes are feasibility (compliance with the study drug regimen for the 6-week administration period and enrolment rate) and safety (the proportion of minor and major adverse events between groups). The primary endpoint for these outcomes will be at 6 weeks. The secondary outcomes are knee extension strength, knee flexion strength, radiographic arthritis progression, thigh muscle circumference, MRI-measured quadriceps muscle volume and patient-reported outcome measures (Knee Osteoarthritis Outcome Score (KOOS), SF-20 and Tegner). The primary endpoint for these outcomes will be at 12 weeks, and the final endpoint will be 24 months, where final radiographic (X-ray) assessment will take place. The primary outcome of compliance will be a calculation of mean compliance between groups, which can be analysed as a t-test after the treatment period. A two-sample, two-sided t-test will compare the clinical (secondary) outcome of greatest interest: knee extension strength at baseline versus week 6 compared between treatment groups. Other secondary outcomes will be compared using a simple linear mixed-effects model. The χ 2 test will be used to determine whether the number of participants who made meaningful changes was different between groups. The null hypotheses are that the rHGH and placebo groups will have no difference in compliance rates, safety events, knee extension strength at 12 weeks and arthritis grade progression at 24 months. Ethics and dissemination This study has been approved by the Sunnybrook Research Institute Research and Ethics Board (#6427) and received a no-objection letter from Health Canada Clinical Trials. The primary sponsor is the Sunnybrook Centre for Clinical Trial Studies (CCTS). The findings of this study will be published in a peer-reviewed journal and presented at orthopaedic conferences. Trial registration number NCT07036003 .