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Liraglutide 3 mg for Knee Osteoarthritis (LOSEIT)

Primary Purpose

Osteoarthritis, Obesity

Status
Completed
Phase
Phase 4
Locations
Denmark
Study Type
Interventional
Intervention
Liraglutide 3 mg (Saxenda)
Liraglutide 3 mg placebo
Sponsored by
Henrik Gudbergsen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Osteoarthritis focused on measuring Liraglutide, Liraglutide 3 mg, Osteoarthritis, Obesity

Eligibility Criteria

18 Years - 74 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Department of Rheumatology

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Liraglutide 3 mg

Liraglutide 3 mg placebo

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

KOOS symptom subscale
Knee injury and Osteoarthritis Outcome Score (KOOS); the symptoms subscale (7 items)
KOOS ADL subscale
Knee injury and Osteoarthritis Outcome Score (KOOS); the Activities of Daily Living (ADL) subscale (17 items)
KOOS sport and recreation subscale
Knee injury and Osteoarthritis Outcome Score (KOOS); the sport and recreation subscale (5 items)
KOOS health related QoL subscale
Knee injury and Osteoarthritis Outcome Score (KOOS); the health related quality of life (QoL) subscale (4 items)
Change in total score in the ICOAP questionnaire
The Intermittent and Constant Osteoarthritis Pain questionnaire (ICOAP); 11 items
Change in the constant pain subscale in the ICOAP questionnaire
The Intermittent and Constant Osteoarthritis Pain questionnaire (ICOAP); 5 items
Change in the intermittent pain subscale in the ICOAP questionnaire
The Intermittent and Constant Osteoarthritis Pain questionnaire (ICOAP); 6 items
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
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
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
Proportion of participants with ≥5% weight loss
The proportion of patients with or with more than a 5% weight loss 52 weeks after randomization
Proportion of participants with ≥10% weight loss
The proportion of patients with or with more than a 10% weight loss 52 weeks after randomization
Change in BMI
Change in body mass index 52 weeks after randomization
Change in waist circumference
Change in waist circumference 52 weeks after randomization
Change in waist/hip circumference ratio
Change in the ratio waist circumference/hip circumference 52 weeks after randomization

Full Information

First Posted
September 14, 2016
Last Updated
March 21, 2019
Sponsor
Henrik Gudbergsen
Collaborators
Novo Nordisk A/S, Cambridge Weight Plan Limited
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1. Study Identification

Unique Protocol Identification Number
NCT02905864
Brief Title
Liraglutide 3 mg for Knee Osteoarthritis
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2019
Overall Recruitment Status
Completed
Study Start Date
November 2016 (undefined)
Primary Completion Date
February 2019 (Actual)
Study Completion Date
March 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Henrik Gudbergsen
Collaborators
Novo Nordisk A/S, Cambridge Weight Plan Limited

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteoarthritis, Obesity
Keywords
Liraglutide, Liraglutide 3 mg, Osteoarthritis, Obesity

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
150 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Liraglutide 3 mg
Arm Type
Experimental
Arm Description
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.
Arm Title
Liraglutide 3 mg placebo
Arm Type
Placebo Comparator
Arm Description
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 Type
Drug
Intervention Name(s)
Liraglutide 3 mg (Saxenda)
Intervention Type
Drug
Intervention Name(s)
Liraglutide 3 mg placebo
Primary Outcome Measure Information:
Title
Change in body weight
Description
One of two co-primary outcomes
Time Frame
Week 0 to 52
Title
KOOS pain subscale
Description
Two of two co-primary outcomes. The Knee injury and Osteoarthritis Outcome Score (KOOS); the pain subscale (9 items)
Time Frame
Week 0 to 52
Secondary Outcome Measure Information:
Title
KOOS symptom subscale
Description
Knee injury and Osteoarthritis Outcome Score (KOOS); the symptoms subscale (7 items)
Time Frame
Week 0 to 52
Title
KOOS ADL subscale
Description
Knee injury and Osteoarthritis Outcome Score (KOOS); the Activities of Daily Living (ADL) subscale (17 items)
Time Frame
Week 0 to 52
Title
KOOS sport and recreation subscale
Description
Knee injury and Osteoarthritis Outcome Score (KOOS); the sport and recreation subscale (5 items)
Time Frame
Week 0 to 52
Title
KOOS health related QoL subscale
Description
Knee injury and Osteoarthritis Outcome Score (KOOS); the health related quality of life (QoL) subscale (4 items)
Time Frame
Week 0 to 52
Title
Change in total score in the ICOAP questionnaire
Description
The Intermittent and Constant Osteoarthritis Pain questionnaire (ICOAP); 11 items
Time Frame
Week 0 to 52
Title
Change in the constant pain subscale in the ICOAP questionnaire
Description
The Intermittent and Constant Osteoarthritis Pain questionnaire (ICOAP); 5 items
Time Frame
Week 0 to 52
Title
Change in the intermittent pain subscale in the ICOAP questionnaire
Description
The Intermittent and Constant Osteoarthritis Pain questionnaire (ICOAP); 6 items
Time Frame
Week 0 to 52
Title
Change in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain subscale
Description
The Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain subscale; 5 items
Time Frame
Week 0 to 52
Title
Change in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) stiffness subscale
Description
The Western Ontario and McMaster Universities Arthritis Index (WOMAC) stiffness subscale; 2 items
Time Frame
Week 0 to 52
Title
Change in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) physical function subscale
Description
The Western Ontario and McMaster Universities Arthritis Index (WOMAC) physical function subscale; 17 items
Time Frame
Week 0 to 52
Title
Proportion of participants with ≥5% weight loss
Description
The proportion of patients with or with more than a 5% weight loss 52 weeks after randomization
Time Frame
Week 0 to 52
Title
Proportion of participants with ≥10% weight loss
Description
The proportion of patients with or with more than a 10% weight loss 52 weeks after randomization
Time Frame
Week 0 to 52
Title
Change in BMI
Description
Change in body mass index 52 weeks after randomization
Time Frame
Week 0 to 52
Title
Change in waist circumference
Description
Change in waist circumference 52 weeks after randomization
Time Frame
Week 0 to 52
Title
Change in waist/hip circumference ratio
Description
Change in the ratio waist circumference/hip circumference 52 weeks after randomization
Time Frame
Week 0 to 52

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
74 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Henrik R Gudbergsen, MD, PhD
Organizational Affiliation
The Parker Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Rheumatology
City
Frederiksberg
State/Province
Capital Region
ZIP/Postal Code
2000
Country
Denmark

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
33471039
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.
Results Reference
derived
PubMed Identifier
32165240
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.
Results Reference
derived
PubMed Identifier
31061017
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.
Results Reference
derived

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Liraglutide 3 mg for Knee Osteoarthritis

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