Radio- KO Radiotherapy for Knee Osteoarthritis Clinical Trial

This is a single-center, single-blinded, sham-controlled, superiority randomized controlled trial at Mayo Clinic, Rochester, Minnesota. A total of 128 adults aged 50-100 years with primary knee OA, Kellgren-Lawrence (KL) grade 2-3, and at least moderate pain will be randomized 1:1 to receive either low dose radiotherapy (LDRT) to the affected knee or an identical sham procedure. LDRT will be delivered at 0.5 Gray (Gy) per fraction x 6 fractions (3 Gy total, delivered over 2 weeks). Non-responders at 2 months will receive an identical second course according to the original allocation. The primary endpoint is the area under the curve (AUC) of the Intermittent and Constant Osteoarthritis Pain (ICOAP) scale collected weekly for 6 months. Secondary and exploratory endpoints include analgesic use, durability of response at 9 and 12 months, and effect modification by age and body mass index. The trial has 80% power (two-sided alpha level of 0.05) to detect a half-standard-deviation difference in AUC between groups on the ICOAP scale over 6 months.

Inclusion criteria

Age 50-100 years with a Mayo Clinic Rochester primary care provider At least moderate constant (ICOAP item A1) or intermittent (ICOAP item B6) pain Diagnosis of primary knee OA (ICD-10 M17.x) without recurrent acute inflammatory flares Joint-line tenderness on examination co-localizes with the reported pain and without a primary extra-articular pain generator Radiographic KL grade 2-3 within the preceding year Ability to complete electronic surveys

Exclusion criteria

Pregnancy or childbearing potential without surgical sterilization Recent knee trauma is causing the current pain History of inflammatory arthritis or hemarthrosis Symptomatic hip OA KL grade 1 or 4 Uncontrolled psychiatric illness Prior ipsilateral intra-articular knee surgery Corticosteroid injection within 3 months or hyaluronic acid injection within 6 months in the ipsilateral knee (or 1 month if no sustained improvement after either) Fibromyalgia Active malignancy requiring treatment Regular current use of opioids, platelet-rich plasma, or acupuncture use for the knee