Butyrate or Intensive Lifestyle Modification in Type 1 Diabetes and Metabolic Dysfunction-Associated Steatotic Liver Disease: A Factorial Randomized Clinical Trial
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Changes in Controlled Attenuation Parameter (CAP) by hepatic elastography (FibroScan®): Controlled Attenuation Parameter (CAP)
研究概览
简要总结
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent in individuals with type 1 diabetes (T1D) and is associated with increased cardiovascular and metabolic risk. However, evidence regarding effective therapeutic strategies for MASLD in T1D remains scarce. Lifestyle modification has shown benefits in obesity and type 2 diabetes, whereas butyrate, a microbiota-derived short-chain fatty acid, has emerged as a potential therapeutic approach because of its anti-inflammatory and metabolic effects. This study aims to evaluate the efficacy of intensive lifestyle modification, butyrate supplementation, or their combination on hepatic steatosis in individuals with T1D and MASLD.
Methods: BEAM-T1D is a factorial, randomized, 6-month, parallel-group, placebo-controlled clinical trial conducted at the Regional University Hospital of Malaga. A total of 200 adults with T1D and MASLD will be randomized (1:1:1:1) to receive: (1) standard lifestyle recommendations plus placebo; (2) intensive lifestyle modification plus placebo; (3) standard lifestyle recommendations plus butyrate; or (4) intensive lifestyle modification plus butyrate. Intensive lifestyle modification includes a hypocaloric Mediterranean diet and promotion of physical activity. Participants randomized to butyrate will receive 2.25 g/day of microencapsulated sodium butyrate. The primary endpoint will be the change in controlled attenuation parameter (CAP) measured by transient elastography (FibroScan®). Secondary outcomes include changes in liver fat content, insulin resistance, metabolic control, body composition, inflammatory markers, gut microbiota composition, and short-chain fatty acid concentrations.
Results: Participant recruitment is expected to begin in October 2025. The study will evaluate the independent and combined effects of butyrate supplementation and intensive lifestyle modification on hepatic steatosis and metabolic outcomes in individuals with T1D and MASLD.
Conclusion: The BEAM-T1D study will provide novel evidence regarding the potential role of butyrate and intensive lifestyle modification in the management of MASLD in T1D. If effective, these interventions could represent feasible and scalable therapeutic strategies for a population with limited evidence-based treatment options.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
Both butyrate and placebo will be packaged and labeled identically to ensure double blinding of participants and study staff.
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-75 years.
- •Type 1 diabetes.
- •MASLD: Defined by a Controlled Attenuation Parameter (CAP) measured by Fibroscan® ≥248 dB/m (40).
- •Signed informed consent.
排除标准
- •History of alcohol consumption > 50 g/day in men or > 30 g/day in women for 3 consecutive months in the last year.
- •Patients with impaired liver function (total bilirubin > 2.0 mg/dL).
- •Hemochromatosis, Wilson's disease, or autoimmune hepatitis.
- •History of cancer (except basal cell carcinoma) in the past 5 years or active cancer of any type.
- •Known infection with HIV, HBV, HCV, or any other infection that may cause liver disease.
- •Severe underlying diseases that, in the investigators' judgment, constitute an exclusion criterion for study participation.
- •Reduced life expectancy.
- •Pregnant or breastfeeding women.
- •Documented history of intolerance/allergy to butyrate.
- •Participation in another clinical trial within 30 days prior to study entry.
- •Inability to comply with scheduled visits.
- •Use of antibiotics, prebiotics, or probiotics (in pharmacological form or as supplements, not as part of usual diet) in the month prior to inclusion in the study.
结局指标
主要结局
Changes in Controlled Attenuation Parameter (CAP) by hepatic elastography (FibroScan®): Controlled Attenuation Parameter (CAP)
时间窗: Baseline, 3 month and 6 month
Measured in dB/m
Changes in Controlled Attenuation Parameter (CAP) by hepatic elastography (FibroScan®): Liver Stiffness Measurement
时间窗: Baseline, 3 month and 6 month
Measured in : kPa
次要结局
- Changes in metabolic control: Time in range (TIR)(Baseline, 3 months and 6 months)
- Changes in metabolic control: Glucose Management Indicator (GMI)(Baseline, 3 months and 6 months)
- Changes in insulin resistance: eGDR(Baseline, 3 months and 6 months)
- Changes in metabolic control: Glucose(Baseline, 3 months and 6 months)
- Changes in metabolic control: HbA1c(Baseline, 3 months and 6 months)
- Changes in metabolic control: Average sensor glucose(Baseline, 3 months and 6 months)
- Changes in metabolic control: Time Above Range (TAR)(Baseline, 3 months and 6 months)
- Changes in metabolic control: Time Below Range (TBR)(Baseline, 3 months and 6 months)
- Changes in body composition: Weight(Baseline, 3 months and 6 months)
- Changes in body composition: Body mass index (BMI)(Baseline, 3 months and 6 months)
- Changes in body composition: Muscular area of rectus anterior(Baseline, 3 months and 6 months)
- Changes in body composition: Fat mass(Baseline, 3 months and 6 months)
- Changes in body composition: Fat-free mass(Baseline, 3 months and 6 months)
- Changes in body composition: Body cellular mass(Baseline, 3 months and 6 months)
- Changes in body composition: Skeletical muscle mass(Baseline, 3 months and 6 months)
- Changes in body composition: Appendicular skeletal muscle mass(Baseline, 3 months and 6 months)
- Changes in blood pressure: Systolic blood pressure(Baseline, 3 months and 6 months)
- Changes in blood pressure: Diastolic blood pressure(Baseline, 3 months and 6 months)
- Changes in lipid profile: Total cholesterol(Baseline, 3 months and 6 months)
- Changes in lipid profile: HDL(Baseline, 3 months and 6 months)
- Changes in lipid profile: LDL(Baseline, 3 months and 6 months)
- Changes in adipokines: Leptin(Baseline, 3 months and 6 months)
- Changes in adipokines: Adiponectin(Baseline, 3 months and 6 months)
- Changes in hepatokines: GDF-15(Baseline, 3 months and 6 months)
- Changes in hepatokines: FGF-21(Baseline, 3 months and 6 months)
- Changes in inflammatory markers: IL-10(Baseline, 3 months and 6 months)
- Changes in inflammatory markers: IL-1b(Baseline, 3 months and 6 months)
- Changes in inflammatory markers: IL-6(Baseline, 3 months and 6 months)
- Changes in inflammatory markers: IL-8(Baseline, 3 months and 6 months)
- Changes in inflammatory markers: IL-12(Baseline, 3 months and 6 months)
- Changes in inflammatory markers: TNF-α(Baseline, 3 months and 6 months)
- Changes in intestinal permeability: Zonuline(Baseline, 3 months and 6 months)
- Changes in short-chain fatty acid levels: Butyrate(Baseline, 3 months and 6 months)
- Changes in gut microbiota: phylum, genus, species(Baseline, 3 months and 6 months)
- Change from baseline in Mediterranean Diet Adherence at 3 and 6 months(Baseline, 3 months and 6 months)
- Change from baseline in Physical Activity Level at 3 and 6 months(Baseline, 3 months and 6 months)
- Change from baseline in Long-term Physical Activity Patterns at 3 and 6 months(Baseline, 3 months and 6 months)
- Changes in body composition: Height(Baseline, 3 months and 6 months)