Clinical trial NCT02905864: Liraglutide 3 mg for Knee Osteoarthritis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Osteoarthritis
Obesity
Keywords: Liraglutide
Liraglutide 3 mg
Osteoarthritis
Obesity
Lead sponsor: Parker Research Institute
Sponsor class: OTHER
Collaborators: name: Novo Nordisk A/S
name: Cambridge Weight Plan Limited
First posted: 2016-09-19
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Change in body weight
timeFrame: Week 0 to 52
measure: KOOS pain subscale
timeFrame: Week 0 to 52
Secondary outcomes:
measure: KOOS symptom subscale
timeFrame: Week 0 to 52
measure: KOOS ADL subscale
timeFrame: Week 0 to 52
measure: KOOS sport and recreation subscale
timeFrame: Week 0 to 52
measure: KOOS health related QoL subscale
timeFrame: Week 0 to 52
measure: Change in total score in the ICOAP questionnaire
timeFrame: Week 0 to 52
measure: Change in the constant pain subscale in the ICOAP questionnaire
timeFrame: Week 0 to 52
measure: Change in the intermittent pain subscale in the ICOAP questionnaire
timeFrame: Week 0 to 52
measure: Change in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain subscale
timeFrame: Week 0 to 52
measure: Change in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) stiffness subscale
timeFrame: Week 0 to 52
measure: Change in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) physical function subscale
timeFrame: Week 0 to 52
measure: Proportion of participants with ≥5% weight loss
timeFrame: Week 0 to 52
measure: Proportion of participants with ≥10% weight loss
timeFrame: Week 0 to 52
measure: Change in BMI
timeFrame: Week 0 to 52
measure: Change in waist circumference
timeFrame: Week 0 to 52
measure: Change in waist/hip circumference ratio
timeFrame: Week 0 to 52
Other outcomes:
Locations:
city: Frederiksberg
country: Denmark
facility: Department of Rheumatology
state: Capital Region
Study officials:
affiliation: The Parker Institute
name: Henrik R Gudbergsen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.