Radio- KO Radiotherapy for Knee Osteoarthritis Clinical Trial (RADIO-KO)

Low-dose RADIOtherapy for Knee Osteoarthritis (RADIO-KO): Protocol for a Single-center, Sham-controlled, Randomized Clinical Trial

The primary aim of this study is to investigate whether low-dose radiotherapy is an effective treatment to reduce the pain of knee osteoarthritis. A secondary aim is to determine whether patients experience any more measurable side effects than those receiving sham treatments.

Study Overview

• Status: Recruiting
• Conditions: Osteoarthritis, Knee
• Intervention / Treatment: Radiation: Low dose radiotherapy; Other: Sham comparator

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 128
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Family Medicine Research Study Coordinators; Phone Number: 507-422-6823; Email: RSTFMSC@mayo.edu

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic
      • Contact: Family Medicine Research Study Coordinators; Phone Number: 507-422-6823; Email: RSTFMSC@mayo.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: Placebo; No radiation therapy	Other: Sham comparator; An identical sham procedure without radiation delivery, administered to the more symptomatic (index) knee on a Monday-Wednesday-Friday schedule over 2 weeks (6 sessions total). Participants who report no improvement in knee pain at their 2-month assessment will receive a second identical round of the sham procedure.
Active Comparator: Low dose radiotherapy; Low dose radiotherapy for knee osteoarthritis	Radiation: Low dose radiotherapy; Low-Dose Radiation Therapy (LDRT) delivered at 0.5 Gy per fraction for 6 fractions, administered on a Monday-Wednesday-Friday schedule over 2 weeks, for a total cumulative dose of 3 Gy. Delivered to the more symptomatic (index) knee. Participants who report no improvement in knee pain at their 2-month assessment will receive a second identical round of LDRT (totaling an additional 3 Gy).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Area Under the Curve (AUC) of ICOAP Scores	Change in the Intermittent and Constant Osteoarthritis Pain (ICOAP) outcome scale weekly for six months after intervention analyzed as area under the curve of patients with Kellgren-Lawrence grade 2-3 knee OA.	Baseline, 6 months
Analgesic use frequency in treatment vs. sham participants	Differences in the rate of improvement between the 2 groups with analysis to include time points of 2 months and 4 months after intervention.	6 months

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Stephen P. Merry, M.D., Mayo Clinic

Study record dates

Study Major Dates

• Study Start (Actual): June 4, 2025
• Primary Completion (Estimated): June 28, 2027
• Study Completion (Estimated): October 29, 2027

Study Registration Dates

• First Submitted: March 7, 2025
• First Submitted That Met QC Criteria: March 14, 2025
• First Posted (Actual): March 20, 2025

Study Record Updates

• Last Update Posted (Actual): September 2, 2026
• Last Update Submitted That Met QC Criteria: August 29, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: Randomized controlled trial; Radiotherapy; Placebos; Pain Management; osteoarthritis, knee
• Additional Relevant MeSH Terms: Neurologic Manifestations; Musculoskeletal Diseases; Nervous System Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Neurobehavioral Manifestations; Osteoarthritis; Perceptual Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Osteoarthritis, Knee; Agnosia; Therapeutics; Radiotherapy
• Other Study ID Numbers: 24-006759

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The datasets used and/or analyzed during the current study, including the trial protocol and statistical analysis plan, will be available from the corresponding author on reasonable request after completion and publication of the trial results.
• IPD Sharing Time Frame: The datasets used and/or analyzed during the current study, including the trial protocol and statistical analysis plan, and any analytic code used by our biostatistician for data analysis will be available from the corresponding author on reasonable request after completion and publication of the trial results.
• IPD Sharing Access Criteria: Qualified researchers who provide a methodologically sound proposal will be able to access the individual participant data (IPD), trial protocol, statistical analysis plan, and analytic code. Data will be shared for the purpose of independent verification of trial results, meta-analysis, or secondary scientific research. To gain access, data requestors must submit a formal research proposal and signed data use agreement to the corresponding author. Data will be securely transferred via password-protected electronic file sharing after approval.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No