Orlistat and Weight Management for Uric Acid Control in Obese Gout: A RCT

Официальное название

Optimization of Blood Uric Acid Control in Obese Gout Patients by Orlistat-Mediated Metabolic Remodeling and Intensive Weight Management: A Randomized Controlled Trial

Обзор

A total of 120 obese gout patients were included in a 24-week double-blind randomized controlled design. The intervention group received orlistat 120 mg tid + UTL + individualized diet-exercise-behavioral reinforcement weight loss program, while the control group received a placebo + UTL + standard recommendations. The primary endpoint was the rate of achieving serum uric acid levels \<360 μmol/L at 24 weeks; secondary endpoints included the proportion of weight loss ≥5%, frequency of gout attacks, and inflammatory indicators such as CRP and IL-1β; the activity of AMPK in PBMCs and the expression of HIF1α and NLRP3 inflammasome-related proteins were also assessed.

Подробное описание

This study employs a double-blind, randomized, controlled trial design. A total of 120 obese gout patients were included and randomly divided into two groups: the intervention group (60 cases): Orlistat (120 mg tid) + UTL + personalized dietary guidance, exercise prescription, and behavioral intervention for a duration of 24 weeks. The control group (60 cases): placebo + UTL + standard weight control recommendations, with the same intervention duration. Both groups received standard uric acid-lowering therapy (such as allopurinol or febuxostat) according to guidelines, with dosages adjusted based on blood uric acid levels and liver and kidney function to maintain stability.

Study Flow and Assessment Indicators Baseline Assessment: demographic data, medical history collection; physical examination (weight, BMI, waist circumference, etc.); laboratory tests (blood routine, urine routine, sedimentation rate, CRP, blood glucose, blood lipids, blood uric acid, liver and kidney function, etc.); collection of peripheral blood mononuclear cells (PBMCs) for mechanistic studies.

Follow-up Assessments (weeks 4, 12, 24): Clinical Indicators: changes in weight, liver and kidney function, blood lipid levels, blood uric acid levels, frequency of gout attacks.

Safety Indicators: recording of adverse events. Mechanistic Study Indicators: detection of AMPK activity in PBMCs, expression levels of HIF1α, NLRP3, ASC, caspase-1, IL-1β, and metabolomics analysis.

Statistics : SPSS 23.0; t-test/Mann-Whitney U for continuous variables, chi-square for categorical data.

Вмешательства

• Препарат Orlistat 120 mg
  Oral capsule, taken after meals, 120 mg three times daily (tid) for 24 weeks.
• Препарат Allopurinol 100 up to 600mg/day
  Standard urate-lowering therapy (e.g., allopurinol or febuxostat), with doses adjusted based on serum uric acid levels and liver/kidney function.
• Препарат Febuxostat 40mg Tab
  Standard urate-lowering therapy (e.g., allopurinol or febuxostat), with doses adjusted based on serum uric acid levels and liver/kidney function.

Первичные конечные точки

• The rate of patients achieving target serum uric acid levels [Срок оценки: 24 weeks]

Вторичные конечные точки (3)

• changes in body weight [Срок оценки: 24 weeks]
• inflammatory markers [Срок оценки: 24 weeks]
• the expression of AMPK-HIF1-inflammasome [Срок оценки: 24 weeks]

Критерии участия

Критерии включения

• Meeting the 2015 ACR/EULAR classification criteria for gout.
• Age 18-70 years.
• BMI ≥28 kg/m².
• Serum uric acid ≥480 μmol/L.
• Willing and able to comply with the study protocol.

Критерии исключения

• Contraindications to orlistat or other gout medications.
• Severe hepatic or renal dysfunction.
• History of severe allergy or adverse reactions to study drugs.
• Pregnant or lactating women.
• Malignancy.
• Secondary gout.
• Poor compliance or inability to cooperate.
• Participation in other clinical trials within the last 3 months.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• General Hospital of Northern Theater Command, PLA — Шэньян

Публикации

• China Obesity Research Collaborative Group.Standardized Reporting for Combined Intervention Studies in Metabolic Diseases (2024 Edition)
• Chinese Rheumatology Association, Chinese Medical Association.Ethical Requirements for Clinical Trial Registration in Gout Diagnosis and Treatment Guidelines (2025 Edition)
• Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University.Operational Guidelines for Chinese Clinical Trial Registry (2023 Edition)
• Beutel ME, Dippel A, Szczepanski M, Thiede R, Wiltink J. Mid-term effectiveness of behavioral and psychodynamic inpatient treatments of severe obesity based on a randomized study. Psychother Psychosom. 2006;75(6):337-45. doi: 10.1159/000095439. PMID 17053334
• Liu S, Lin X, Tao M, Chen Q, Sun H, Han Y, Yang S, Gao Y, Qu S, Chen H. Efficacy and safety of orlistat in male patients with overweight/obesity and hyperuricemia: results of a randomized, double-blind, placebo-controlled trial. Lipids Health Dis. 2024 Mar 11;23(1):77. doi: 10.1186/s12944-024-02047-7. PMID 38468241
• Yip ASY, Leong S, Teo YH, Teo YN, Syn NLX, See RM, Wee CF, Chong EY, Lee CH, Chan MY, Yeo TC, Wong RCC, Chai P, Sia CH. Effect of sodium-glucose cotransporter-2 (SGLT2) inhibitors on serum urate levels in patients with and without diabetes: a systematic review and meta-regression of 43 randomized controlled trials. Ther Adv Chronic Dis. 2022 Mar 23;13:20406223221083509. doi: 10.1177/20406223221083 PMID 35342538
• Sridharan K, Alkhidir MMOH. Hypouricemic effect of sodium glucose transporter-2 inhibitors: a network meta-analysis and meta-regression of randomized clinical trials. Expert Rev Endocrinol Metab. 2025 Mar;20(2):139-146. doi: 10.1080/17446651.2025.2456504. Epub 2025 Jan 21. PMID 39835962
• Chen X, Chen S, Ren Q, Niu S, Pan X, Yue L, Li Z, Zhu R, Jia Z, Chen X, Zhen R, Ban J. Metabolomics Provides Insights into Renoprotective Effects of Semaglutide in Obese Mice. Drug Des Devel Ther. 2022 Nov 9;16:3893-3913. doi: 10.2147/DDDT.S383537. eCollection 2022. PMID 36388084

Идентификаторы

NCT: NCT07326839 · 2025JH2/101800052

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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