Effect of Liraglutide on Body Weight and Pain in Overweight or Obese Patients With Knee Osteoarthritis: A Randomised, Double Blind, Placebo-controlled, Parallel Group, Single-centre Trial
Overview
- Phase
- Phase 4
- Status
- Completed
- Sponsor
- Henrik Gudbergsen
- Enrollment
- 150
- Locations
- 1
- Primary Endpoint
- KOOS pain subscale
Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 74 Years (Adult, Older Adult)
- Sex
- All
- Accepts 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
Arms & Interventions
Liraglutide 3 mg
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.
Intervention: Liraglutide 3 mg (Saxenda) (Drug)
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.
Intervention: Liraglutide 3 mg placebo (Drug)
Outcomes
Primary Outcomes
KOOS pain subscale
Time Frame: Week 0 to 52
Two of two co-primary outcomes. The Knee injury and Osteoarthritis Outcome Score (KOOS); the pain subscale (9 items)
Change in body weight
Time Frame: Week 0 to 52
One of two co-primary outcomes
Secondary Outcomes
- Change in the intermittent pain subscale in the ICOAP questionnaire(Week 0 to 52)
- Change in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain subscale(Week 0 to 52)
- Change in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) stiffness subscale(Week 0 to 52)
- KOOS symptom subscale(Week 0 to 52)
- KOOS ADL subscale(Week 0 to 52)
- KOOS sport and recreation subscale(Week 0 to 52)
- KOOS health related QoL subscale(Week 0 to 52)
- Change in total score in the ICOAP questionnaire(Week 0 to 52)
- Change in the constant pain subscale in the ICOAP questionnaire(Week 0 to 52)
- Change in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) physical function subscale(Week 0 to 52)
- Change in waist/hip circumference ratio(Week 0 to 52)
- Proportion of participants with ≥5% weight loss(Week 0 to 52)
- Change in BMI(Week 0 to 52)
- Change in waist circumference(Week 0 to 52)
- Proportion of participants with ≥10% weight loss(Week 0 to 52)
Investigators
Henrik Gudbergsen
MD, PhD
Parker Research Institute