Butyrate or Intensive Lifestyle Modification in Type 1 Diabetes and Metabolic Dysfunction-Associated Steatotic Liver Disease

Official title

Butyrate or Intensive Lifestyle Modification in Type 1 Diabetes and Metabolic Dysfunction-Associated Steatotic Liver Disease: A Factorial Randomized Clinical Trial

Overview

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.

Interventions

• Other Intensive lifestyle modification (hypocaloric Mediterranean diet and promotion of physical activity)
  Participants will be advised to follow a Mediterranean diet, characterized by the use of olive oil as the main source of fat, regular consumption of vegetables, fruits, legumes, and fish, reduced consumption of red meat and processed meats, and elimination of sugar-sweetened beverages, industrial pastries, and confectionery. The Mediterranean diet will include a 30% energy restriction based on estimated energy needs (Harris-Benedict equation). Participants will also be advised to perform ≥150 mi
• Dietary supplement Butyrate
  Participants randomized to this group will receive microencapsulated sodium butyrate (MSB). Each sachet contains 750 mg sodium butyrate and 1750 mg triglyceride matrix (total 2,500 mg). Participants will take 3 sachets daily (total daily dose: 2.25 g butyrate): one in the morning, one at midday, and one in the evening.
• Dietary supplement Intensive lifestyle modification + butyrate
  Participants will undergo both intensive lifestyle modification and receive butyrate as described above. This study will be placebo-controlled: participants not randomized to butyrate will receive placebo sachets identical in size, color, appearance, and taste to the investigational product but without butyrate. Placebo will also be taken three times daily following the same schedule.

Primary outcome measures

• Changes in Controlled Attenuation Parameter (CAP) by hepatic elastography (FibroScan®): Controlled Attenuation Parameter (CAP) [Time frame: Baseline, 3 month and 6 month]
• Changes in Controlled Attenuation Parameter (CAP) by hepatic elastography (FibroScan®): Liver Stiffness Measurement [Time frame: Baseline, 3 month and 6 month]

Secondary outcome measures (12)

• Changes in insulin resistance: eGDR [Time frame: Baseline, 3 months and 6 months]
• Changes in metabolic control: Glucose [Time frame: Baseline, 3 months and 6 months]
• Changes in metabolic control: HbA1c [Time frame: Baseline, 3 months and 6 months]
• Changes in metabolic control: Average sensor glucose [Time frame: Baseline, 3 months and 6 months]
• Changes in metabolic control: Glucose Management Indicator (GMI) [Time frame: Baseline, 3 months and 6 months]
• Changes in metabolic control: Time in range (TIR) [Time frame: Baseline, 3 months and 6 months]
• Changes in metabolic control: Time Above Range (TAR) [Time frame: Baseline, 3 months and 6 months]
• Changes in metabolic control: Time Below Range (TBR) [Time frame: Baseline, 3 months and 6 months]
• Changes in body composition: Weight [Time frame: Baseline, 3 months and 6 months]
• Changes in body composition: Body mass index (BMI) [Time frame: Baseline, 3 months and 6 months]
• Changes in body composition: Muscular area of rectus anterior [Time frame: Baseline, 3 months and 6 months]
• Changes in body composition: Fat mass [Time frame: Baseline, 3 months and 6 months]

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Factorial

Masking

Double blind

Primary purpose

Treatment

Study locations

Spain · 1 center

• Hospital Regional Universitario de Málaga, FIMABIS — Málaga

Identifiers

NCT: NCT07684248 · BEAM-T1D Study

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗