Liraglutide 3 mg for Knee Osteoarthritis
- Conditions
- ObesityOsteoarthritis
- Interventions
- Registration Number
- NCT02905864
- Lead Sponsor
- Henrik Gudbergsen
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 150
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Liraglutide 3 mg Liraglutide 3 mg (Saxenda) Arm description: Subjects will be up titrated to liraglutide 3 mg QD and stay on that dose for the remainder of the 52-week drug intervention period. Drug: Liraglutide 3 mg QD administered in a 6 mg/mL, 3 mL pen for subcutaneous injection. Dose escalation scheme: Initial dosage of 0.6 mg per day, escalated bi-weekly by 0.6 mg to 3 mg per day over a total of 8 weeks. Liraglutide 3 mg placebo Liraglutide 3 mg placebo Arm description: Subjects will be up titrated to liraglutide 3 mg placebo QD and stay on that dose for the remainder of the 52-week drug intervention period. Drug: Liraglutide 3 mg placebo QD administered in a 6 mg/mL drug equivalent volumes, 3 mL pen for subcutaneous injection. Dose escalation scheme: Initial dosage of a 0.6 mg drug equivalent volume per day, escalated bi-weekly by an 0.6 mg drug equivalent volume per day to a 3 mg drug equivalent volume per day over a total of 8 weeks.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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 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
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 symptom subscale Week 0 to 52 Knee injury and Osteoarthritis Outcome Score (KOOS); the symptoms subscale (7 items)
KOOS ADL subscale Week 0 to 52 Knee injury and Osteoarthritis Outcome Score (KOOS); the Activities of Daily Living (ADL) subscale (17 items)
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 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 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
Change in waist/hip circumference ratio Week 0 to 52 Change in the ratio waist circumference/hip circumference 52 weeks after randomization
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
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
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
Trial Locations
- Locations (1)
Department of Rheumatology
🇩🇰Frederiksberg, Capital Region, Denmark