Clinical Evaluation of Psoriatic Arthritis Treated With Liraglutide. The PLAQUE Study: Psoriatic Arthritis Treated With Liraglutide Therapy: a QUality of Life and Efficacy Study
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- The change in the proportion of patients achieving an ACR 20% improvement response in patients with psoriatic arthritis receiving liraglutide for 12 weeks compared to placebo
研究概览
简要总结
Exploratory, double-blind randomized, placebo-controlled, Phase II study to evaluate the effect(s) of short-term administration of liraglutide, a GLP-1R (glucagon-like peptide-1 receptor) agonist on joint and skin inflammation in patients with active Psoriatic Arthritis.
详细描述
The primary purpose of this study is to determine whether short-term (12-week) administration of the GLP-1R agonist, liraglutide, will improve joint and skin swelling in patients with active Psoriatic Arthritis compared to placebo.
Background: Psoriatic Arthritis is a systemic inflammatory T-cell disorder affecting the joints and spine, and is associated with an elevated risk for Type 2 Diabetes and Cardiovascular Disease. In addition to classical effects on glycemic-lowering, GLP-1R agonists are anti-diabetes agents which also have anti-inflammatory properties that may be clinically useful for patients with inflammatory diseases, particularly those with co-morbid metabolic disease. While a few small exploratory studies in patients with psoriasis have demonstrated that GLP-1R agonists reduce the severity of skin plaques, dedicated prospective, randomized mechanistic studies evaluating potential mechanisms by which GLP-1R agonists exert anti-inflammatory action(s) in humans with inflammatory disease is lacking.
Objectives: Primary objective is to evaluate the clinical efficacy of short-term liraglutide (GLP-1R agonist) administration on the severity of joint and skin inflammation in patients with active Psoriatic Arthritis. Secondary objectives are to determine whether short-term liraglutide administration in patients with active psoriatic arthritis will 1) modify the degree of impaired glucose tolerance, underlying b-cell function and cardiovascular risk factor profiles, 2) improve patient-centered outcomes such as quality of life and functionality, 3) modify specific sub-populations of T-cells and affect their differentiation and activation, and 4) modify activation of circulating immune cells, pro-inflammatory cytokines, and hormones.
Design: Double-blind, randomized, placebo-controlled trial, Phase II.
Patient population: 34 patients between with active Psoriatic Arthritis meeting CASPAR (ClASsification criteria for Psoriatic ARthritis).
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with active psoriatic arthritis (3 tender and swollen joints) meeting CASPAR study group criteria
排除标准
- •BMI > 35 kg/m2
- •Uncontrolled diabetes, HbA1c > 10.5%
- •Current biological treatment for any inflammatory disorder within the past three months
- •renal dysfunction (eGFR < 50 ml/min/1.73m or macroalbuminuria >300mg)
- •hepatic dysfunction (AST (aspartate aminotransferase), ALT (alanine aminotransferase), Total bilirubin > 3 times upper limit of normal)
- •history of pancreatitis or personal or family history of medullary thyroid cancer, c-cell hyperplasia, or MEN-2 syndrome
- •current pregnancy or current breast feeding
- •use of DPP-4 (dipeptidyl peptidase-4 inhibitor) or GLP-1 receptor agonist within 2 months (washout is permitted)
- •drug or alcohol dependence
- •resting tachycardia > 100 bpm or conduction abnormalities associated with tachycardia
- •current enrollment in any other clinical trial
- •symptomatic gastroparesis
- •concomitant serious medical conditions
- •all medication for the treatment of Psoriatic Arthritis such as MTX (methotrexate) < 25 mg, LFN (leflunomide) < 20 mg, and NSAIDs (non-steroidal anti-inflammatory drugs) will have been used at stable doses for at least 4 weeks, having been initiated at least 3 months prior to study start (8 weeks before screening, 4 weeks before baseline) for MTX and LFN and at least 4 weeks for NSAIDs
研究组 & 干预措施
Interventional arm
liraglutide 0.6mg sc daily for 1 week, 1.2mg sc daily for 11 weeks
干预措施: liraglutide (Drug)
Placebo arm
Placebo sc daily for 12 weeks, volume titration at week 2 to mirror liraglutide arm
干预措施: Placebo (Other)
结局指标
主要结局
The change in the proportion of patients achieving an ACR 20% improvement response in patients with psoriatic arthritis receiving liraglutide for 12 weeks compared to placebo
时间窗: Baseline to 12 weeks, liraglutide compared to placebo
Proportion of patients achieving an ACR (American College of Rheumatology) 20% improvement response. ACR 20 is a composite rheumatological endpoint which includes swollen joint count, tender joint count, pain, physician global assessment, patient global assessment, HAQ (health assessment questionnaire), CRP (c reactive protein).
次要结局
- The effect(s) of liraglutide on cardiovascular disease risk factors in patients with psoriatic arthritis receiving liraglutide for 12 weeks compared to those receiving placebo(Baseline to 12 weeks)
- The change in glucose tolerance in patients with psoriatic arthritis with glucose intolerance at baseline who receive liraglutide for 12 weeks compared to those receiving placebo(Baseline to 12 weeks)
- The effect(s) of liraglutide on the enumeration of circulating T-cell subpopulations, and on activation of circulating T-cell subpopulations(Baseline to 12 weeks)
- The change in the psoriasis area and severity index (PASI) in patients with psoriatic arthritis receiving liraglutide for 12 weeks compared to those receiving placebo(Baseline to 12 weeks)
- The change in quality of life measured by validated quality of life questionnaires in patients with psoriatic arthritis receiving liraglutide for 12 weeks compared to those receiving placebo(Baseline to 12 weeks)