Isocaloric Navy-Bean Substitution in Adults With MASLD

Official title

Randomized Feasibility Trial of Isocaloric Navy-Bean Substitution in Adults With MASLD (Metabolic Dysfunction-Associated Steatotic Liver Disease)

Overview

This study is a 24-week randomized crossover feasibility trial evaluating an isocaloric navy-bean dietary substitution in 40 adults with metabolic dysfunction-associated steatotic liver disease (MASLD) and intermediate-stage (F2-F3) fibrosis. Participants are randomized to one of two sequences-habitual diet followed by a navy-bean-rich diet, or a navy-bean-rich diet followed by habitual diet-with each 12-week phase guided by registered dietitians so that navy beans replace an equivalent caloric load without changing total energy intake. The primary aim is to establish feasibility and acceptability, measured by recruitment and retention, adherence with biomarker (plasma pipecolic-acid) concordance, and patient acceptability.

Detailed description

Rationale: Diet acts on MASLD progression through the gut-liver axis, in which microbial composition, intestinal barrier integrity, and microbe-derived metabolites influence hepatic inflammation, steatosis, and fibrosis. Navy beans supply fermentable fiber, resistant starch, and polyphenols that nourish short-chain-fatty-acid-producing microbes, and prior human work (the BE GONE trial) demonstrated increased microbial diversity, enrichment of beneficial taxa, and favorable metabolomic and proteomic shifts following an 8-week navy-bean intervention. An isocaloric substitution approach isolates bean-specific biologic effects from weight change, addressing a major confounder in MASLD dietary trials.

Interventions

• Other Dietary Supplement/Behavioral: Navy Bean-Rich Diet
  Isocaloric substitution in which navy beans replace an equivalent caloric load of the habitual diet under individualized registered-dietitian counseling, with resting-metabolic-rate-based prescription and a gradual dose ramp-up (½ to 1 cup). Total energy intake is maintained.
• Other Habitual Diet (Control)
  Participants maintain their usual diet without the navy-bean substitution during the assigned control period

Primary outcome measures

• Feasibility composite score [Time frame: Week 24]

Secondary outcome measures (5)

• Proportion of participants rating the navy-bean intervention as acceptable [Time frame: At Week 12 and Week 24]
• Proportion of visits with Isocaloric fidelity [Time frame: through Week 24]
• Change in hepatic fat by MRI-PDFF [Time frame: Baseline (Week 0), Week 12, and Week 24]
• Change in alanine aminotransferase (ALT) [Time frame: Baseline (Week 0), Week 12, and Week 24]
• Change in liver stiffness by MRE [Time frame: Baseline (Week 0), Week 12, and Week 24]

Eligibility criteria

Inclusion criteria

• Adults 18-75 years of age with capacity to provide informed consent
• Enrolled in the Mount Sinai Steatotic Liver Disease registry with a clinical diagnosis of MASLD, confirmed by imaging (MRI-PDFF or VCTE) or prior biopsy
• Intermediate-stage fibrosis (F2-F3) confirmed by one of the following (most recent qualifying result): VCTE (FibroScan) 8.0-14 kPa, MRE 3.0-4.6 kPa (2D EPI @ 60 Hz), or liver biopsy read as F2-F3
• Body mass index 25-45 kg/m²
• Stable medications for ≥12 weeks for diabetes, hypertension, dyslipidemia, or weight management
• Alcohol intake below MASLD thresholds (≤15 drinks/week for men, ≤10 drinks/week for women)
• Willing and able to consume study navy beans and complete dietary recalls (ASA-24/DSQ)
• Able to undergo MRI and MRE (no contraindications) and attend study visits
• Agrees to biospecimen collection (blood, stool, saliva) and patient-reported outcomes

Exclusion criteria

• Other chronic liver disease (hepatitis B, hepatitis C, autoimmune hepatitis, hemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency, primary biliary cholangitis, primary sclerosing cholangitis)
• Decompensated liver disease (ascites, variceal bleeding, encephalopathy) or Child-Pugh B/C cirrhosis, or clinical portal hypertension/decompensation
• Heavy alcohol use above MASLD thresholds, or alcohol use disorder within 12 months
• Legume/bean allergy or intolerance
• Initiation or dose change of antidiabetic, lipid-lowering, antihypertensive, or weight-loss medications within the past 12 weeks, or anticipated changes during the trial
• Recent initiation of agents known to affect hepatic fat or fibrosis (e.g., GLP-1 receptor agonist, SGLT2 inhibitor, pioglitazone, resmetirom) within 12 weeks
• Use of hepatotoxic drugs likely to confound liver enzymes in the prior 12 weeks (per investigator judgment)
• New supplements targeting weight loss, liver health, or the microbiome within 8-12 weeks (e.g., berberine, high-dose omega-3, pre/probiotics)
• Antibiotics, probiotics, or colonoscopy preparation within 8 weeks
• Planned bariatric surgery or other major weight-loss intervention during the study
• Recent weight change >5% within 8-12 weeks prior to baseline
• Severe gastrointestinal disease (inflammatory bowel disease, celiac disease, short bowel syndrome) that may impair tolerance
• Uncontrolled diabetes (HbA1c >10%), severe renal dysfunction (eGFR <45), or unstable cardiovascular, thyroid, or psychiatric illness
• Pregnant or breastfeeding
• Contraindications to MRI (e.g., non-compatible implants, severe claustrophobia)
• Participation in another interventional study within the last 30 days

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

Crossover

Masking

Single blind

Primary purpose

Other

Study locations

United States · 1 center

• Mount Sinai Hospital — New York

Publications

• Zhang X, Irajizad E, Hoffman KL, Fahrmann JF, Li F, Seo YD, Browman GJ, Dennison JB, Vykoukal J, Luna PN, Siu W, Wu R, Murage E, Ajami NJ, McQuade JL, Wargo JA, Long JP, Do KA, Lampe JW, Basen-Engquist KM, Okhuysen PC, Kopetz S, Hanash SM, Petrosino JF, Scheet P, Daniel CR. Modulating a prebiotic food source influences inflammation and immune-regulating gut microbes and metabolites: insights from PMID 38040541
• Zhang X, Browman G, Siu W, Basen-Engquist KM, Hanash SM, Hoffman KL, Okhuysen PC, Scheet P, Petrosino JF, Kopetz S, Daniel CR. The BE GONE trial study protocol: a randomized crossover dietary intervention of dry beans targeting the gut microbiome of overweight and obese patients with a history of colorectal polyps or cancer. BMC Cancer. 2019 Dec 18;19(1):1233. doi: 10.1186/s12885-019-6400-z. PMID 31852462
• Baxter BA, Oppel RC, Ryan EP. Navy Beans Impact the Stool Metabolome and Metabolic Pathways for Colon Health in Cancer Survivors. Nutrients. 2018 Dec 22;11(1):28. doi: 10.3390/nu11010028. PMID 30583518
• Bajaj JS, Reddy KR, Tandon P, Lai JC, O'Leary JG, Wong F, Garcia-Tsao G, Vargas HE, Kamath PS, Biggins SW, Vutien P, Shaw J, Limon Miro AT, Bera C, McGinley JP, Sikaroodi M, Bush BJ, Thacker LR, Gillevet PM. Salivary microbiome and serum metabolomics add to clinical biomarkers to predict 6-month hospitalizations in a multicenter cirrhosis outpatient cohort. Hepatology. 2026 Jun 1;83(6):1483-1494. PMID 40632657

Identifiers

NCT: NCT07730853 · GCO 25-1954

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗