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

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, Ultrasound

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

  • The Parker Institute and Department of Radiology at Bispebjerg and Frederiksberg Hospital

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 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.

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 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)

Secondary Outcome Measures

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.)
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)
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)

Full Information

First Posted
October 7, 2016
Last Updated
March 21, 2019
Sponsor
Henrik Gudbergsen
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1. Study Identification

Unique Protocol Identification Number
NCT02931383
Brief Title
Ultrasound of the Knee in Obese Patients With Knee Osteoarthritis; Weight Maintenance
Acronym
US-LOSEIT-II
Official Title
Ultrasound of the Knee in Obese Patients With Knee Osteoarthritis Following Liraglutide Treatment, Investigating the Impact on Inflammation
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

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

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, Ultrasound

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 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.
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 the degree of inflammation in the knee-joint (Greyscale-score)
Description
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)
Time Frame
Week 0 to 52
Secondary Outcome Measure Information:
Title
Change in knee-joint effusion
Description
Change in effusion will be assessed via the US knee OA musculoskeletal ultrasound score (MUS) score (Riecke BF et al.)
Time Frame
Week 0 to 52
Title
Change in the degree of inflammation in the knee-joint (Greyscale-size)
Description
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)
Time Frame
Week 0 to 52
Title
Change in the degree of inflammation in the knee-joint (Doppler-score)
Description
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)
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
Facility Information:
Facility Name
The Parker Institute and Department of Radiology at Bispebjerg and Frederiksberg Hospital
City
Frederiksberg
State/Province
Capital Region
ZIP/Postal Code
2000
Country
Denmark

12. IPD Sharing Statement

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Ultrasound of the Knee in Obese Patients With Knee Osteoarthritis; Weight Maintenance

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