Liraglutide 3 mg for Knee Osteoarthritis

Obesity Clinical Trial

— LOSEIT  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02905864
• Other study ID #: 137.00
• Status: Completed
• Phase: Phase 4
• Start date: November 2016
• Est. completion date: March 2019

Study information

• Verified date: March 2019
• Source: Parker Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: March 2019
• Est. primary completion date: February 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 74 Years

Eligibility

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

Related Conditions & MeSH terms

• Obesity
• Osteoarthritis
• Osteoarthritis, Knee

Intervention

Drug:
• Liraglutide 3 mg (Saxenda)

• Liraglutide 3 mg placebo

Locations

Country	Name	City	State
Denmark	Department of Rheumatology	Frederiksberg	Capital Region

Sponsors (3)

Lead Sponsor	Collaborator
Henrik Gudbergsen	Cambridge Weight Plan Limited, Novo Nordisk A/S

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in body weight	One of two co-primary outcomes	Week 0 to 52
Primary	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	KOOS symptom subscale	Knee injury and Osteoarthritis Outcome Score (KOOS); the symptoms subscale (7 items)	Week 0 to 52
Secondary	KOOS ADL subscale	Knee injury and Osteoarthritis Outcome Score (KOOS); the Activities of Daily Living (ADL) subscale (17 items)	Week 0 to 52
Secondary	KOOS sport and recreation subscale	Knee injury and Osteoarthritis Outcome Score (KOOS); the sport and recreation subscale (5 items)	Week 0 to 52
Secondary	KOOS health related QoL subscale	Knee injury and Osteoarthritis Outcome Score (KOOS); the health related quality of life (QoL) subscale (4 items)	Week 0 to 52
Secondary	Change in total score in the ICOAP questionnaire	The Intermittent and Constant Osteoarthritis Pain questionnaire (ICOAP); 11 items	Week 0 to 52
Secondary	Change in the constant pain subscale in the ICOAP questionnaire	The Intermittent and Constant Osteoarthritis Pain questionnaire (ICOAP); 5 items	Week 0 to 52
Secondary	Change in the intermittent pain subscale in the ICOAP questionnaire	The Intermittent and Constant Osteoarthritis Pain questionnaire (ICOAP); 6 items	Week 0 to 52
Secondary	Change in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain subscale	The Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain subscale; 5 items	Week 0 to 52
Secondary	Change in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) stiffness subscale	The Western Ontario and McMaster Universities Arthritis Index (WOMAC) stiffness subscale; 2 items	Week 0 to 52
Secondary	Change in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) physical function subscale	The Western Ontario and McMaster Universities Arthritis Index (WOMAC) physical function subscale; 17 items	Week 0 to 52
Secondary	Proportion of participants with =5% weight loss	The proportion of patients with or with more than a 5% weight loss 52 weeks after randomization	Week 0 to 52
Secondary	Proportion of participants with =10% weight loss	The proportion of patients with or with more than a 10% weight loss 52 weeks after randomization	Week 0 to 52
Secondary	Change in BMI	Change in body mass index 52 weeks after randomization	Week 0 to 52
Secondary	Change in waist circumference	Change in waist circumference 52 weeks after randomization	Week 0 to 52
Secondary	Change in waist/hip circumference ratio	Change in the ratio waist circumference/hip circumference 52 weeks after randomization	Week 0 to 52