Liraglutide 3 mg for Knee Osteoarthritis

NCT02905864 | Completed Phase 4 DMC

• 1 other identifier: 137.00
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

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.

Conditions

Osteoarthritis; Obesity

Keywords

Liraglutide; Liraglutide 3 mg; Osteoarthritis; Obesity

Outcome Measures

Primary Outcomes (2)

• Change in body weight

  One of two co-primary outcomes

  Week 0 to 52

• KOOS pain subscale

  Two of two co-primary outcomes. The Knee injury and Osteoarthritis Outcome Score (KOOS); the pain subscale (9 items)

  Week 0 to 52

Secondary Outcomes (15)

• 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

Study Arms (2)

Liraglutide 3 mg

EXPERIMENTAL

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.

Drug: Liraglutide 3 mg (Saxenda)

Liraglutide 3 mg placebo

PLACEBO COMPARATOR

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

Interventions

Liraglutide 3 mg (Saxenda) DRUG

Liraglutide 3 mg

Liraglutide 3 mg placebo DRUG

Liraglutide 3 mg placebo

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Henrik Gudbergsen: lead
• Novo Nordisk A/S: collaborator
• Cambridge Weight Plan Limited: collaborator

Study Sites (1)

Department of Rheumatology

Frederiksberg, Capital Region, 2000, Denmark

Location

Related Publications (4)

• Poulsen AS, Stisen ZR, Skougaard M, Christensen R, Overgaard A, Gudbergsen H, Jacobsen S, Balslev-Clausen AP, Henriksen M, Kristensen LE, Bliddal H. Effect of weight loss and liraglutide on neutrophil gelatinase-associated lipocalin levels among individuals with overweight and knee osteoarthritis: Exploratory analyses of a randomized controlled trial. Osteoarthr Cartil Open. 2025 Jan 3;7(1):100562. doi: 10.1016/j.ocarto.2024.100562. eCollection 2025 Mar.

  PMID: 39877802 DERIVED

• Gudbergsen H, Overgaard A, Henriksen M, Waehrens EE, Bliddal H, Christensen R, Nielsen SM, Boesen M, Knop FK, Astrup A, Rasmussen MU, Bartholdy C, Daugaard CL, Ellegaard K, Heitmann BL, Bartels EM, Danneskiold-Samsoe B, Kristensen LE. Liraglutide after diet-induced weight loss for pain and weight control in knee osteoarthritis: a randomized controlled trial. Am J Clin Nutr. 2021 Feb 2;113(2):314-323. doi: 10.1093/ajcn/nqaa328.

  PMID: 33471039 DERIVED

• Daugaard CL, Henriksen M, Riis RGC, Bandak E, Nybing JD, Hangaard S, Bliddal H, Boesen M. The impact of a significant weight loss on inflammation assessed on DCE-MRI and static MRI in knee osteoarthritis: a prospective cohort study. Osteoarthritis Cartilage. 2020 Jun;28(6):766-773. doi: 10.1016/j.joca.2020.02.837. Epub 2020 Mar 10.

  PMID: 32165240 DERIVED

• Gudbergsen H, Henriksen M, Waehrens EE, Overgaard A, Bliddal H, Christensen R, Boesen MP, Knop FKK, Astrup A, Rasmussen MU, Bartholdy C, Daugaard C, Bartels EM, Ellegaard K, Heitmann BL, Kristensen LE. Effect of liraglutide on body weight and pain in patients with overweight and knee osteoarthritis: protocol for a randomised, double-blind, placebo-controlled, parallel-group, single-centre trial. BMJ Open. 2019 May 5;9(5):e024065. doi: 10.1136/bmjopen-2018-024065.

  PMID: 31061017 DERIVED

MeSH Terms

Conditions

Osteoarthritis; Obesity

Interventions

Liraglutide

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide 1; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Henrik R Gudbergsen, MD, PhD

  The Parker Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: September 14, 2016
• First Posted: September 19, 2016
• Study Start: November 1, 2016
• Primary Completion: February 1, 2019
• Study Completion: March 1, 2019
• Last Updated: March 25, 2019

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)