Ultrasound of the Knee in Obese Patients With Knee Osteoarthritis; Weight Maintenance (US-LOSEIT-II)

Ultrasound of the Knee in Obese Patients With Knee Osteoarthritis Following Liraglutide Treatment, Investigating the Impact on Inflammation

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 Overview

• Status: Completed
• Conditions: Obesity; Osteoarthritis
• Intervention / Treatment: Drug: Liraglutide 3 mg (Saxenda); Drug: Liraglutide 3 mg placebo

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Phase 4

Contacts and Locations

Study Locations

• Denmark
  • Capital Region
    • Frederiksberg, Capital Region, Denmark, 2000
      • The Parker Institute and Department of Radiology at Bispebjerg and Frederiksberg Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 72 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 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.	Drug: Liraglutide 3 mg placebo
Experimental: 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.	Drug: Liraglutide 3 mg (Saxenda)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the degree of inflammation in the knee-joint (Greyscale-score)	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)	Week 0 to 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in knee-joint effusion	Change in effusion will be assessed via the US knee OA musculoskeletal ultrasound score (MUS) score (Riecke BF et al.)	Week 0 to 52
Change in the degree of inflammation in the knee-joint (Greyscale-size)	Change will be assessed by grey-scale ultrasound in the suprapatellar, the medial, and the lateral recess´ (sum of size-scores (mm) of these three positions)	Week 0 to 52
Change in the degree of inflammation in the knee-joint (Doppler-score)	Change will be assessed by Doppler ultrasound in the suprapatellar, the medial, and the lateral recess´ (sum-score (0-9), derived from these three positions)	Week 0 to 52

Collaborators and Investigators

• Sponsor: Henrik Gudbergsen

Study record dates

Study Major Dates

• Study Start: November 1, 2016
• Primary Completion (Actual): February 1, 2019
• Study Completion (Actual): March 1, 2019

Study Registration Dates

• First Submitted: October 7, 2016
• First Submitted That Met QC Criteria: October 10, 2016
• First Posted (Estimate): October 13, 2016

Study Record Updates

• Last Update Posted (Actual): March 25, 2019
• Last Update Submitted That Met QC Criteria: March 21, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Ultrasound; Obesity; Osteoarthritis; Liraglutide; Liraglutide 3 mg
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Liraglutide
• Other Study ID Numbers: 137.07