Using tirzepatide to help patients with obesity and knee osteoarthritis avoid knee replacement

Effect of Subcutaneous Tirzepatide Once-weekly in Patients With Obesity and Knee Osteoarthritis (STOP KNEE-OA): A Randomized, Double-Blind, Placebo-Controlled Trial

This study is testing if a weekly injection of tirzepatide can help people with obesity and knee osteoarthritis avoid needing knee replacement surgery.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 352 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Melbourne (Academic / other)
• Locations: 4 sites (Fitzroy, Victoria and 3 other locations)
• Trial ID: NCT06191848 on ClinicalTrials.gov

What this trial studies

This trial investigates the effects of tirzepatide, administered as a weekly subcutaneous injection, on patients suffering from obesity and knee osteoarthritis. Participants will be randomly assigned to receive either tirzepatide or a placebo over a period of 72 weeks. The primary goal is to determine if tirzepatide can decrease the number of patients who ultimately require knee replacement surgery due to their condition. The study aims to provide insights into the potential benefits of tirzepatide in managing obesity-related knee issues.

Who should consider this trial

Good fit: Ideal candidates are individuals with a BMI of 30 or greater who have moderate-to-severe knee osteoarthritis and have previously struggled with weight loss.

Not a fit: Patients who do not have obesity or those with mild knee osteoarthritis may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could help patients avoid knee replacement surgery and improve their quality of life.

How similar studies have performed: While there have been studies on tirzepatide for obesity, this specific application for knee osteoarthritis is novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

* Have a body mass index of ≥ to 30 kg/m2.
* Report one or more previous unsuccessful attempt to lose body weight via lifestyle modification.
* Have been deemed eligible to enter the waiting list for primary knee replacement for the treatment of osteoarthritis in the target joint by an orthopaedic surgeon at one of the participating study sites.
* Have moderate-to-severe knee osteoarthritis in the target joint, defined as a Kellgren-Lawrence grade two or greater.
* Be willing to and capable of learning how to self-inject the study drug and follow study procedures for the duration of the trial.
* Provide informed consent to study participation in line with the requirements of the human research ethics committee of the study site.

Female participants must:

* Not be currently pregnant or breastfeeding AND
* Not be of reproductive potential, defined as:
* Infertile due to surgical sterilization or congenital anomaly, OR
* Post-menopausal defined as:
* A woman over the age of 40 years with spontaneous cessation of menses for at least 12 consecutive months (in the absence of medications known to induce amenorrhea), with a follicle-stimulating hormone ≥40mIU/mL, and a negative pregnancy test prior to study entry, OR
* A woman over the age of 55 years with cessation of menses for at least 12 consecutive months (in the absence of medications known to induce amenorrhea), OR
* A woman over the age of 55 years that has commenced hormone replacement therapy after a documented diagnosis of menopause.

Exclusion Criteria:

Participant will be ineligible for inclusion if they meet any of the following criteria:

* Have been deemed eligible to enter the waiting list for knee replacement in the contralateral knee by an orthopaedic surgeon at one of the participating study sites.
* Have used any prescription medications intended to promote weight loss (e.g., tirzepatide, liraglutide, semaglutide) in the three months prior to screening.
* Have previously undergone any surgical or endoscopic procedure intended to promote weight loss.
* Have been diagnosed with type 1 diabetes mellitus (T1DM) or T2DM
* Have laboratory evidence indicative of diabetes mellitus during screening.
* Have personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
* Have an active malignancy (excluding basal or squamous cell skin cancer).
* Have had a transplanted organ or awaiting an organ transplant
* Have received chronic systemic glucocorticoid therapy (for more than 14 days) in prior 3 months or have a significant, active autoimmune abnormality (e.g., lupus or rheumatoid arthritis) that the study doctor deems likely to require systemic glucocorticoid therapy during the next 18 months.
* Have any other medical conditions, abnormal laboratory tests or concomitant medications that make them unsuitable for participation:

  * Have a clinically significant gastric emptying abnormality.
  * Have had a history of acute or chronic pancreatitis.
  * Have obesity induced by other endocrinologic disorders
  * Have an unstable psychiatric disorder
  * Have a Patient Health Questionnaire (PHQ-9) score of \>15 during screening
  * Have been deemed by the study doctor to be actively suicidal,
* Have answered "yes" to questions 4 or 5 on the "Suicidal Ideation" section of the Columbia-Suicide Severity Rating Scale (C-SSRS) during screening, OR
* Have answered yes to any questions in the "Suicidal Behaviour" section of the C-SSRS during screening. AND
* The behaviour or ideation occurred in the last month

  * Have uncontrolled hypertension (systolic blood pressure above or equal to 160 mmHg and/or diastolic blood pressure above or equal to 100 mmHg)
  * Have had within the past 6 months prior to randomisation any of the following: acute myocardial infarction, cerebrovascular accident, unstable angina, or hospitalisation due to congestive cardiac failure (are also exclusion criteria for elective knee replacement)
  * Have severe renal impairment defined as an eGFR \<30 mL/min/1.73 m2 at screening visit.
  * Have thyroid-stimulating hormone outside of the range of 0.4 to 6.0 mIU/L at screening visit
  * Have acute or chronic hepatitis or abnormal liver function tests as measured by either alanine aminotransferase or alkaline phosphatase \>200 IU.
  * Have any other known contraindication to any glucagon-like peptide-1 receptor agonists.
* Are study site personnel, or immediate family of a member of the study site.
* Have been enrolled in any other study of an investigational product within the past ninety days or are currently enrolled in such a study.

Where this trial is running

Fitzroy, Victoria and 3 other locations

• St Vincents Hospital Melbourne — Fitzroy, Victoria, Australia (Recruiting)
• Western Health — Melbourne, Victoria, Australia (Recruiting)
• Austin Health-Repatriation Hospital — Melbourne, Victoria, Australia (Recruiting)
• Eastern Health — Melbourne, Victoria, Australia (Recruiting)

Study contacts

• Principal investigator: Michelle M Dowsey — University of Melbourne
• Study coordinator: Angela Cochrane

Conditions Obesity; Knee Osteoarthritis; Osteoarthritis, Knee; Osteoarthritis; Total knee replacement