Adult (= 18 years of age) overweight or obese patients (BMI = 27 kg/m2 ) above 18 years of age with knee osteoarthritis (OA) defined by clinical diagnosis of knee OA according to the 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) MedDRA version: 19.0 Level: LLT Classification code 10023476 Term: Knee osteoarthritis System Organ Class: 100000004859 MedDRA version:
Conditions
Interventions
Trade Name: Saxenda
Product Name: saxenda
Pharmaceutical Form: Solution for injection in pre-filled pen
INN or Proposed INN: LIRAGLUTIDE
CAS Number: 204656-20-2
Concentration unit: mg/ml milligram(s)/
Sponsors
The Parker Institute, Bispebjerg and Frederiksberg Hospital, The Capital Region of Denmark
Eligibility
Sex/Gender
All
Inclusion 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 =65 years) yes F.1.3.1 Number of subjects for this age range 75
Exclusion criteria
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 • Use of opioids or similar strong analgesics • 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) • Pregnancy or insufficient anti-conception therapy for female fertile patients • Breast-feeding • Estimated glomerular filtration rate (eGFR) 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To establish the efficacy of a diet intervention combined with liraglutide 3 mg or liraglutide 3 mg placebo in inducing and maintaining weight loss over 52 weeks • To investigate the efficacy of a diet intervention combined with liraglutide 3 mg or liraglutide 3 mg placebo as a pain-reducing management strategy over 52 weeks ;Secondary Objective: • To compare the efficacy of a diet intervention combined with either liraglutide 3 mg or liraglutide 3 mg placebo for 52 weeks on knee OA-related patient reported stiffness and function scores • To compare the efficacy of a diet intervention combined with either liraglutide 3 mg or liraglutide 3 mg placebo for 52 weeks on intermittent and constant knee pain intensity, pain related distress, and the impact of OA pain on quality of life • To compare the efficacy of a diet intervention combined with either liraglutide 3 mg or liraglutide 3 mg placebo for 52 weeks on the proportion of patients loosing at least 5% or at least 10% of their body weight • To compare the efficacy of a diet intervention combined with either liraglutide 3 mg or liraglutide 3 mg placebo at week 52 on waist circumference, waist/hip ratio, and BMI ;Primary end point(s): In order to demonstrate that liraglutide 3 mg not only safely and efficaciously lowers body weight, but also reduce pain, these endpoints have been selected as co-primary. • Change in body weight Time frame; week 0 to 52 • Change in the KOOS pain subscale Time frame; week 0 to 52 ;Timepoint(s) of evaluation of this end point: Week 0 and 52 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Confirmatory secondary endpoints • Change in the KOOS symptom subscale Time frame; week 0 to 52 • Change in the KOOS ADL subscale Time frame; week 0 to 52 • Change in the KOOS sport and recreation subscale Time frame; week 0 to 52 • Change in the KOOS health related QoL subscale Time frame; week 0 to 52 • Change in the WOMAC pain subscale Time frame; week 0 to 52 • Change in the WOMAC stiffness subscale Time frame; week 0 to 52 • Change in the WOMAC function subscale Time frame; week 0 to 52 • Change in total score and subscales in the ICOAP questionnaire Time frame; week 0 to 52 • Proportion of participants with =5% weight loss Time frame; week 0 to 52 • Proportion of participants with =10% weight loss Time frame; week 0 to 52 • Change in BMI Time frame; week 0 to 52 • Change in waist circumference and in waist/hip ratio Time frame; week 0 to 52 Supportive secondary endpoints • Change in C-reactive protein (CRP), glycosylated haemoglobin (HbA1c), fasting plasma glucose (FPG), ALT, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG), and total cholesterol (TC) Time frame; week 0 to 52 • Change in resting heart rate and blood pressure Time frame; week 0 to 52 • Change in the TRIM-weight questionnaire Time frame; week 0 to 52 • Change in SF-36 total as well as mental and physical composite scores Time frame; week 0 to 52 • Change in IWQoL-lite questionnaire Time frame; week 0 to 52 • Proportion of participants responding according to the O-OA Time frame; week 0 to 52 • Proportion of participants meeting metabolic syndrome criteria Time frame; week 0 to 52 • Proportion of participants meeting pre-diabetes criteria Time frame; week 0 to 52 Safety endpoints • Changes outside the reference limits (+/- 2 SD) in haemoglobin, thrombocytes, leucocytes, differential cell count, creatinine, and electrolytes Timing; at visits T0 as well as T15 or Tx • Changes outside the reference limits (+ 150 %) in ALT and CRP Timing; | — |
Countries
Denmark
Contacts
Public ContactPrimary/ Principal Investigator
The Parker Institute, Bispebjerg and Frederiksberg Hospital, The Capital Region of Denmark
Outcome results
None listed