Obesity, Osteoarthritis
Conditions
Keywords
Liraglutide, Liraglutide 3 mg, Osteoarthritis, Obesity
Brief summary
A randomised, double blind, placebo-controlled, parallel group, and single-centre trial investigating the effect of liraglutide on body weight and pain in overweight or obese patients with knee osteoarthritis. Patients will be subjected to a run-in diet intervention phase (week -8 to 0) including a low-calorie diet and dietetic counselling. At week 0 patients will be randomised to receive either liraglutide 3 mg or liraglutide 3 mg placebo as an add-on to dietetic guidance on re-introducing regular foods and a focus on continued motivation to engage in a healthy lifestyle.
Interventions
Sponsors
Novo Nordisk A/S
Cambridge Weight Plan Limited
Henrik Gudbergsen
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 74 Years
Healthy volunteers
No
Inclusion criteria
* Informed consent obtained * Clinical diagnosis of knee OA (American College of Rheumatology (ACR) criteria) confirmed by radiology but restricted to definite radiographic OA at early to moderate-stages (Kellgren-Lawrence grades 1, 2, or 3) * Age ≥ 18 years and \< 75 years * Body mass index (BMI) ≥ 27 kg/m2 * Stable body weight during the previous 3 months (\< 5 kg self-reported weight change) * Motivated for weight loss
Exclusion criteria
* On-going participation, or participation within the last 3 months, in an organised weight loss programme (or within the last 3 months) * Current or history of treatment with medications that may cause significant weight gain for at least 3 months before this trial * Current use or use within three months before this trial of GLP-1 receptor agonist, pramlintide, sibutramine, orlistat, zonisamide, topiramate, or phentermine * Type 1 diabetes * Type 2 diabetes treated with glucose-lowering drugs other than metformin * Alloplasty in target knee joint (see section 6.3) * End stage disease in target knee joint (Kellgren-Lawrence grade 4) * Immuno-inflammatory disease * Chronic wide-spread pain * Pregnancy or insufficient anti-conception therapy for female fertile patients * Breast-feeding * Estimated glomerular filtration rate (eGFR) \< 60 ml/min/1.73 m2 * Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 3 x above upper normal range (UNR) * Surgery scheduled for the trial duration period, except for minor surgical procedures * Surgical procedures such as arthroscopy or injections into a knee within 3 months prior to enrolment * Previous surgical treatment for obesity (excluding liposuction \>1 year before trial entry) * Thyroid stimulating hormone (TSH) outside of the range of 0.4-6.0 mIU/L * Obesity secondary to endocrinologic or eating disorders or to treatment with medicinal products that may cause weight gain * Family or personal history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 * Inflammatory bowel disease * Congestive heart failure, New York Heart Association (NYHA) class III-IV * Diabetic gastroparesis * History of or current diagnosis of pancreatitis (acute and/or chronic) or pancreatic cancer * History of cancer with the exception of in-situ malignancies of the skin or cervix uteri * History of major depressive disorder, a PHQ-9 (Patient Health Questionnaire-9) score of more than 15, or a history of other severe psychiatric disorders or diagnosis of an eating disorder * Subjects with a lifetime history of a suicide attempt or history of any suicidal behaviour within the past month before entry into the trial * Inability to speak Danish fluently * A mental state impeding compliance with the program * Use of opioids or similar strong analgesics * Allergic reactions to the active ingredients of Saxenda, such as hypotension, palpitations, dyspnoea and oedema
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in body weight | Week 0 to 52 | One of two co-primary outcomes |
| KOOS pain subscale | Week 0 to 52 | Two of two co-primary outcomes. The Knee injury and Osteoarthritis Outcome Score (KOOS); the pain subscale (9 items) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| KOOS sport and recreation subscale | Week 0 to 52 | Knee injury and Osteoarthritis Outcome Score (KOOS); the sport and recreation subscale (5 items) |
| KOOS health related QoL subscale | Week 0 to 52 | Knee injury and Osteoarthritis Outcome Score (KOOS); the health related quality of life (QoL) subscale (4 items) |
| Change in total score in the ICOAP questionnaire | Week 0 to 52 | The Intermittent and Constant Osteoarthritis Pain questionnaire (ICOAP); 11 items |
| Change in the constant pain subscale in the ICOAP questionnaire | Week 0 to 52 | The Intermittent and Constant Osteoarthritis Pain questionnaire (ICOAP); 5 items |
| Change in the intermittent pain subscale in the ICOAP questionnaire | Week 0 to 52 | The Intermittent and Constant Osteoarthritis Pain questionnaire (ICOAP); 6 items |
| Change in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain subscale | Week 0 to 52 | The Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain subscale; 5 items |
| KOOS symptom subscale | Week 0 to 52 | Knee injury and Osteoarthritis Outcome Score (KOOS); the symptoms subscale (7 items) |
| Change in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) physical function subscale | Week 0 to 52 | The Western Ontario and McMaster Universities Arthritis Index (WOMAC) physical function subscale; 17 items |
| Proportion of participants with ≥5% weight loss | Week 0 to 52 | The proportion of patients with or with more than a 5% weight loss 52 weeks after randomization |
| Proportion of participants with ≥10% weight loss | Week 0 to 52 | The proportion of patients with or with more than a 10% weight loss 52 weeks after randomization |
| Change in BMI | Week 0 to 52 | Change in body mass index 52 weeks after randomization |
| Change in waist circumference | Week 0 to 52 | Change in waist circumference 52 weeks after randomization |
| Change in waist/hip circumference ratio | Week 0 to 52 | Change in the ratio waist circumference/hip circumference 52 weeks after randomization |
| Change in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) stiffness subscale | Week 0 to 52 | The Western Ontario and McMaster Universities Arthritis Index (WOMAC) stiffness subscale; 2 items |
| KOOS ADL subscale | Week 0 to 52 | Knee injury and Osteoarthritis Outcome Score (KOOS); the Activities of Daily Living (ADL) subscale (17 items) |
Countries
Denmark
Outcome results
None listed