Ultrasound of the Knee in Obese Patients With Knee Osteoarthritis Following Liraglutide Treatment, Investigating the Impact on Inflammation
Overview
- Phase
- Phase 4
- Status
- Completed
- Sponsor
- Henrik Gudbergsen
- Enrollment
- 150
- Locations
- 1
- Primary Endpoint
- Change in the degree of inflammation in the knee-joint (Greyscale-score)
Overview
Brief Summary
This is a substudy to a randomised trial investigating the effect of liraglutide on body weight and pain in overweight or obese patients with knee osteoarthritis (OA) (NCT02905864). In the parent trial, patients will be subjected to an 8-week diet intervention phase including a low-calorie diet and dietetic counseling, after which 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.
This substudy aims to investigate the impact of, and subsequent change of, joint inflammation and clinical symptoms, in obese patients with knee osteoarthritis following a randomisation to Liraglutide 3 mg or Liraglutide 3 mg placebo treatment between weeks 0-52.
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 once daily (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
Change in the degree of inflammation in the knee-joint (Greyscale-score)
Time Frame: Week 0 to 52
Change will be assessed by grey-scale ultrasound (US) in the suprapatellar, the medial, and the lateral recess´ (sum-score (0-9), derived from these three positions)
Secondary Outcomes
- Change in knee-joint effusion(Week 0 to 52)
- Change in the degree of inflammation in the knee-joint (Greyscale-size)(Week 0 to 52)
- Change in the degree of inflammation in the knee-joint (Doppler-score)(Week 0 to 52)
Investigators
Henrik Gudbergsen
MD, PhD
Parker Research Institute