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
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- KOOS pain subscale
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 74 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Liraglutide 3 mg
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.
干预措施: Liraglutide 3 mg (Saxenda) (Drug)
Liraglutide 3 mg placebo
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.
干预措施: Liraglutide 3 mg placebo (Drug)
结局指标
主要结局
KOOS pain subscale
时间窗: Week 0 to 52
Two of two co-primary outcomes. The Knee injury and Osteoarthritis Outcome Score (KOOS); the pain subscale (9 items)
Change in body weight
时间窗: Week 0 to 52
One of two co-primary outcomes
次要结局
- Change in the intermittent pain subscale in the ICOAP questionnaire(Week 0 to 52)
- Change in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain subscale(Week 0 to 52)
- Change in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) stiffness subscale(Week 0 to 52)
- KOOS symptom subscale(Week 0 to 52)
- KOOS ADL subscale(Week 0 to 52)
- KOOS sport and recreation subscale(Week 0 to 52)
- KOOS health related QoL subscale(Week 0 to 52)
- Change in total score in the ICOAP questionnaire(Week 0 to 52)
- Change in the constant pain subscale in the ICOAP questionnaire(Week 0 to 52)
- Change in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) physical function subscale(Week 0 to 52)
- Change in waist/hip circumference ratio(Week 0 to 52)
- Proportion of participants with ≥5% weight loss(Week 0 to 52)
- Change in BMI(Week 0 to 52)
- Change in waist circumference(Week 0 to 52)
- Proportion of participants with ≥10% weight loss(Week 0 to 52)
研究者
Henrik Gudbergsen
MD, PhD
Parker Research Institute