Effects of Semaglutide on Clinical Outcomes and Metabolic Inflammation in Psoriasis: A Randomized, Triple-Blind, Placebo-Controlled Clinical Trial
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 62
- 试验地点
- 1
- 主要终点
- Effect of GLP-1 Receptor Agonists on SCD-1 Activity
研究概览
简要总结
This study will evaluate the effects of oral semaglutide in combination with topical corticosteroid/calcipotriol on clinical outcomes and metabolic inflammation in patients with plaque psoriasis and overweight/obesity and/or type 2 diabetes mellitus. A total of 62 participants will be randomized to receive either semaglutide plus topical corticosteroid/calcipotriol or placebo plus topical corticosteroid/calcipotriol for 12 weeks. Clinical efficacy will be assessed using the Psoriasis Area and Severity Index (PASI), and quality of life will be evaluated using DLQI, PROMIS-29, and EQ-5D-5L. Systemic inflammatory markers will also be measured to assess metabolic inflammation.
详细描述
Psoriasis is a chronic inflammatory skin disease frequently associated with metabolic comorbidities, including obesity and type 2 diabetes mellitus. Increasing evidence suggests that systemic metabolic inflammation may contribute to psoriasis severity and treatment response. Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist widely used in the management of type 2 diabetes and obesity, has demonstrated anti-inflammatory effects that may be relevant to psoriasis.
This study is a randomized, triple-blind, placebo-controlled clinical trial designed to evaluate the effects of oral semaglutide on clinical disease activity, quality of life, and metabolic inflammatory markers in patients with plaque psoriasis and overweight/obesity and/or type 2 diabetes mellitus.
A total of 62 participants will be enrolled and randomized in a 1:1 ratio to one of two treatment groups. One group will receive oral semaglutide in combination with topical corticosteroid/calcipotriol cream, while the comparator group will receive oral placebo in combination with topical corticosteroid/calcipotriol cream. All participants will receive treatment for 12 weeks.
Clinical assessments will be performed at baseline and at weeks 4, 8, and 12. Disease severity and clinical response will be evaluated using the Psoriasis Area and Severity Index (PASI) at each visit. Patient-reported quality of life will be assessed using the Dermatology Life Quality Index (DLQI), the Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29), and the EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L) at baseline and at week 12.
Blood samples will be collected at baseline and at week 12 to evaluate systemic inflammatory and metabolic biomarkers, allowing assessment of changes in metabolic inflammation associated with treatment.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female participants aged ≥18 years at the time of randomization.
- •Clinical diagnosis of plaque psoriasis with Psoriasis Area and Severity Index (PASI) ≥3 and body surface area (BSA) ≥3%.
- •Body mass index (BMI) ≥25 kg/m², consistent with overweight or obesity.
- •Participants with or without type 2 diabetes mellitus.
- •Participants with diabetes must be on stable antidiabetic therapy (no changes in medication or dosage within the previous 3 months) and have adequate glycemic control, defined as HbA1c ≤9.0% at baseline.
- •No use of systemic psoriasis therapies (e.g., methotrexate, cyclosporine) for at least 8 weeks prior to randomization.
- •No use of biologic therapies for at least 3 months prior to randomization.
排除标准
- •Diagnosis of a non-plaque psoriasis subtype, including pustular, guttate, nail, inverse, psoriatic arthritis, or erythrodermic psoriasis.
- •Pregnancy or breastfeeding at the time of screening or enrollment.
- •Insulin-dependent diabetes mellitus or current use of sulfonylureas.
- •Active malignancy at the time of screening.
- •History of thyroid neoplasia.
- •Presence of autoimmune diseases.
- •Use of systemic therapies within 8 weeks prior to randomization.
- •Use of biologic therapies within 3 months prior to randomization.
- •Renal insufficiency.
- •Heart failure.
- •Hepatic insufficiency.
- •History of pancreatitis.
- •Current treatment with other GLP-1 receptor agonists.
- •History of inflammatory bowel disease.
- •Known allergy to starch.
研究组 & 干预措施
Semaglutide group
A total of 31 participants will be randomly assigned to the semaglutide intervention group.
干预措施: Semaglutide (Rybelsus®) (Drug)
Placebo group
A total of 31 participants will be randomly assigned to the placebo intervention group.
干预措施: Placebo (Drug)
结局指标
主要结局
Effect of GLP-1 Receptor Agonists on SCD-1 Activity
时间窗: Baseline to Week 12
Change in SCD-1 activity, assessed via acylcarnitine profile (µmol/L), from baseline to Week 12.
次要结局
- Change in Body Weight in Participants with Type 2 Diabetes(Baseline and Week 12)
- Change in Body Weight in Participants without Type 2 Diabetes(Baseline to Week 12)
- Change in Body Mass Index (BMI) in Participants with Type 2 Diabetes(Baseline to Week 12)
- Change in Body Mass Index (BMI) in Participants without Type 2 Diabetes(Baseline to Week 12)
- Change in Serum IL-6 in Participants with Type 2 Diabetes(Baseline to Week 12)
- Change in Serum IL-6 in Participants without Type 2 Diabetes(Baseline to Week 12)
- Change in Serum IL-17 in Participants without Type 2 Diabetes(Baseline to Week 12)
- Change in Serum IL-17 in Participants with Type 2 Diabetes(Baseline to Week 12)
- Change in Serum IL-23 in Participants with Type 2 Diabetes(Baseline to Week 12)
- Change in Serum IL-23 in Participants without Type 2 Diabetes(Baseline to Week 12)
- Change in Serum TNF-α in Participants with Type 2 Diabetes(Baseline to Week 12)
- Change in Serum IL-6 by Diabetes Status(Baseline and Week 12)
- Change in Waist-to-Hip Ratio(Baseline and Week 12)
- Change in Blood Pressure(Baseline and Week 12)
- Change in Serum TNF-α in Participants without Type 2 Diabetes(Baseline to Week 12)
- Change in Serum Tumor Necrosis Factor-Alpha (TNF-α)(Baseline and Week 12)
- Change in Serum C-Reactive Protein (CRP)(Baseline and Week 12)
- Change in Erythrocyte Sedimentation Rate (ESR)(Baseline and Week 12)
- Change in Serum TNF-α by Diabetes Status(Baseline and Week 12)
- Change in Serum CRP by Diabetes Status(Baseline and Week 12)
- Change in ESR by Diabetes Status(Baseline and Week 12)
- Change in HbA1c(Baseline to Week 12)
- Change in HDL Cholesterol(Baseline to Week 12)
- Change in LDL Cholesterol(Baseline to Week 12)
- Change in VLDL Cholesterol(Baseline to Week 12)
- Change in Triglycerides(Baseline to Week 12)
- Change in Serum C-Reactive Protein (CRP) in Participants with Type 2 Diabetes(Baseline to Week 12)
- Change in Serum C-Reactive Protein (CRP) in Participants without Type 2 Diabetes(Baseline to Week 12)
- Change in Erythrocyte Sedimentation Rate (ESR) in Participants with Type 2 Diabetes(Baseline to Week 12)
- Change in Erythrocyte Sedimentation Rate (ESR) in Participants without Type 2 Diabetes(Baseline to Week 12)
- Proportion of Participants Achieving Psoriasis Area and Severity Index (PASI) 75(Weeks 4, 8, and 12)
- Change in Body Weight(Baseline and Week 12)
- Change in Fasting Plasma Glucose(Baseline and Week 12)
- Change in Total Cholesterol(Baseline and Week 12)
- Correlation Between Metabolic Parameters and PASI Improvement(Baseline to Week 12)
- Change in Dermatology Life Quality Index (DLQI)(Baseline and Week 12)
- Correlation Between Psoriasis Severity and Quality of Life Measures(Baseline to Week 12)
- Change in Serum Interleukin-6 (IL-6)(Baseline and Week 12)
- Correlation Between PASI and Inflammatory Biomarkers(Baseline to Week 12)
- PASI Response by Type 2 Diabetes Status(Baseline to Week 12)
- Correlation Between Baseline Glycemic Control and Change in Psoriasis Severity(Baseline to Week 12)
- Incidence and Type of Adverse Events(Up to Week 12)
- Change in Body Mass Index (BMI)(Baseline and week 12)
- Change in Waist Circumference(Baseline and Week 12)
- Change in Hip Circumference(Baseline and Week 12)
- Time to First Achievement of PASI 75(Up to Week 12)
- Change in PROMIS-29 Profile Score(Baseline and Week 12)
- Change in EQ-5D-5L Index Score(Baseline and Week 12)
- Change in Serum Interleukin-17 (IL-17)(Baseline and Week 12)
- Change in Serum Interleukin-23 (IL-23)(Baseline and Week 12)
- Correlation Between Baseline Glycemic Control and Change in Metabolic Parameters(Baseline to Week 12)
- Change in Body Mass Index (BMI) by Diabetes Status(Baseline and Week 12)
- Change in Acylcarnitine Profile by Diabetes Status(Baseline and Week 12)
- Change in Serum IL-17 by Diabetes Status(Baseline and Week 12)
- Change in Serum IL-23 by Diabetes Status(Baseline and Week 12)
研究者
Jorge Valdespino Valdes
MD
Hospital Universitario Dr. Jose E. Gonzalez