Gout, Obesity
Conditions
Keywords
Obese, Gout, Orlistat, Metabolic Reprogramming, Weight Control, Uric acid, AMPK, HIF1, NLRP3
Brief summary
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.
Detailed description
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.
Interventions
DRUGOrlistat 120 mg
Oral capsule, taken after meals, 120 mg three times daily (tid) for 24 weeks.
Standard urate-lowering therapy (e.g., allopurinol or febuxostat), with doses adjusted based on serum uric acid levels and liver/kidney function.
Standard urate-lowering therapy (e.g., allopurinol or febuxostat), with doses adjusted based on serum uric acid levels and liver/kidney function.
Sponsors
Shengjing Hospital
The People's Hospital of Liaoning Province
XueMei Guo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Randomized open-label, two-arm parallel control
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Meeting the 2015 ACR/EULAR classification criteria for gout. 2. Age 18-70 years. 3. BMI ≥28 kg/m². 4. Serum uric acid ≥480 μmol/L. 5. Willing and able to comply with the study protocol.
Exclusion criteria
1. Contraindications to orlistat or other gout medications. 2. Severe hepatic or renal dysfunction. 3. History of severe allergy or adverse reactions to study drugs. 4. Pregnant or lactating women. 5. Malignancy. 6. Secondary gout. 7. Poor compliance or inability to cooperate. 8. Participation in other clinical trials within the last 3 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The rate of patients achieving target serum uric acid levels | 24 weeks | The rate of patients achieving serum uric acid \< 360 μmol/L |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| changes in body weight | 24 weeks | The proportion of patients with a weight loss of ≥5%,the unit of weight is Kilogram(Kg). |
| inflammatory markers | 24 weeks | changes in the frequency of gout attacks, changes in inflammatory markers (CRP, IL-1β, etc.).The unit of CRP is mg/L,the unit of ESR is mm/h,the unit of IL- 1β is pg/mL. |
| the expression of AMPK-HIF1-inflammasome | 24 weeks | changes in the expression of key molecules in the AMPK-HIF1-inflammasome axis. |
Countries
China
Contacts
Primary ContactXueMei GUO, MS
Outcome results
None listed