Knee Osteoarthritis, Obesity, Osteoarthritis, Knee
Conditions
Keywords
Osteoarthritis, Obesity, Total knee replacement
Brief summary
This is a trial of tirzepatide in people with obesity and knee osteoarthritis. The main purpose of this study is to see if tirzepatide can reduce number of these participants who require a knee replacement. Participants will be randomized to take a weekly injection of tirzepatide or a placebo for a total of 72 weeks.
Interventions
DRUGTirzepatide
Participants will receive tirzepatide subcutaneously
DRUGPlacebo
Participants will receive placebo subcutaneously
Sponsors
Eli Lilly and Company
University of Melbourne
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of patients who undergo knee replacement in the target joint | within 72 weeks of randomization | Percentage of patients who undergo knee replacement in the target joint |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Osteoarthritis Function | Baseline, Week 72 | Change from Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Function Subscale Score. The WOMAC Function subscale has 17-items, with a possible range of 0-68, with higher scores indicating worse functional impairment. |
| Osteoarthritis Stiffness | Baseline, Week 72 | Change from Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale Score. The WOMAC Stiffness subscale has 2-items, with a possible range of 0-8, with higher score indicating worse stiffness. |
| Percentage change in bodyweight | Baseline, Week 72 | Mean percentage change in body weight at 72 weeks after randomization |
| ≥5% body weight reduction | Baseline, Week 72 | Percentage of participants with ≥5% body weight reduction at 72 weeks after randomization |
| ≥10% body weight reduction | Baseline, Week 72 | Percentage of participants with ≥10% body weight reduction at 72 weeks after randomization |
| ≥20% body weight reduction | Baseline, Week 72 | Percentage of participants with ≥20% body weight reduction at 72 weeks after randomization |
| Physical Health | Baseline, Week 72 | Mean change in the 36-item Short Form (SF-36) Physical Component Summary at 72 weeks after randomization. The SF-36 Physical Component Summary, a lower score indicates poorer physical health. |
| Osteoarthritis Pain | Baseline, Week 72 | Change from Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score. The WOMAC Pain subscale has 5-items, with a possible score range of 0-20, with higher scores indicating worse pain. |
| Physical Activity | Baseline, Week 72 | Mean change in Physical Activity Scale for the Elderly (PASE) score at 72 weeks after randomization. The PASE has 12-items with a total score range from 0-400 or more, with higher scores indicating greater physical activity. |
| Non-opioid prescription pain medication use | Baseline, between 68-72 weeks | Proportion of participants reporting use of non-opioid prescription analgesics between 68-72 weeks after randomization |
| Opioid prescription pain medication use | Baseline, between 68-72 weeks | Proportion of participants reporting use of prescription opioid analgesics between 68-72 weeks after randomization |
| Mean change in use of prescription opioid pain medication | Baseline, between 68-72 weeks | Mean change in prescription opioids dose at 72 weeks after randomization |
| Participant willingness to undergo knee replacement surgery | within the 72 weeks since randomization | Proportion of patients who undergo knee replacement in the target joint within 72 weeks of randomization or re-enter the waiting list within 72 weeks of randomization. |
| Long-term (5-year) progression to knee replacement | within 260 weeks of randomization | Percentage of patients who undergo knee replacement in the target joint within 5-years |
| Long-term (10-year) progression to knee replacement | within 520 weeks of randomization | Percentage of patients who undergo knee replacement in the target joint within 10-years |
| Mental Health | Baseline, Week 72 | Mean change in the 36-item Short Form Survey (SF-36) Mental Component Summary at 72 weeks after randomization. For the SF-36 Mental Component Summary, a lower score indicates poorer mental health. |
Countries
Australia
Contacts
Primary ContactAngela Cochrane
Backup ContactMichelle M Dowsey
Outcome results
None listed