Effect of Ancestry Supplementation in Subjects With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

Official title

Effect of Ancestry Supplementation on the Abundance of Beneficial Bacterial Genera in the Gut Microbiota in Subjects With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

Overview

The goal of this clinical trial is to evaluate the effect of Ancestry, a supplement made from Mexican-origin foods (nopal, cacao, and cricket) in adults with Metabolic dysfunction-associated steatotic liver disease (MASLD). The main questions it aims to answer are: * Does the supplementation with Ancestry improve the hepatic steatosis grade in participants with MASLD? * Does the supplementation improve biochemical and anthropometric parameters in participants with MASLD? * Does the supplementation enrich the abundance of beneficial bacteria in the gut microbiota of participants? Researchers will compare the supplement group to a placebo group to see if the supplement is effective. Participants will: * Take the supplement or a placebo every day for 3 months. * Receive nutritional guidance from a trained dietitian to control dietary intake. * Attend follow-up clinic visits every month for monitoring and checkups.

Detailed description

The study will follow a randomized double-blind design. Randomization will be performed in matched pairs according to sex, age (±3 years), diabetes status, body mass index (BMI), and degree of hepatic steatosis. An investigator not involved in participant follow-up will generate a coded randomization list to assign participants to the supplement or placebo group.

Investigators involved in participant assessments and sample processing, as well as study participants, will remain blinded to group allocation throughout the intervention. The supplement and placebo will be provided in identical packaging to maintain blinding.

Hepatic steatosis and fibrosis will be evaluated using the FibroScan Expert 630 device (Echosens, Paris, France), a vibration-controlled transient elastography (VCTE) system, by a physician specialized in hepatology and gastroenterology.

Nutritional consultations and dietary prescriptions will be provided by a trained nutritionist following the clinical recommendations established by the European Association for the Study of the Liver (EASL) and the American Association for the Study of Liver Diseases (AASLD) for MASLD management.

Anthropometric assessment will include height and waist, abdominal, and hip circumferences measured using a Lufkin Rosscraft W606 metallic measuring tape. Body composition analysis will be performed using the InBody 720 bioimpedance analyzer (Biospace), which will provide measurements of body weight, body fat percentage, and visceral fat. All measurements will be interpreted according to standardized guidelines and reference cut-off values.

Interventions

• Dietary supplement Ancestry
  The active intervention consists of a daily oral supplement in powder form, containing a 30g mixture of dehydrated Mexican-origin foods: nopal (10g), cocoa powder (10g), and cricket (10g). The supplement will be consumed once daily for 3 months. Participants will be instructed to mix the entire 30g powder content with 250 ml of water and consume it immediately.
• Other Placebo
  The placebo consists of a daily oral supplement in powder form, containing a mixture of calcium caseinate (10g) and maltodextrin (5g). This matched formulation is designed to equalize the caloric value and macronutrient profile of the active intervention. The placebo will be consumed once daily for 3 months. Participants will be instructed to mix the entire powder content with 250 ml of water and consume it immediately.

Primary outcome measures

• A ≥1 grade hepatic steatosis improvement with no liver fibrosis worsening [Time frame: From enrollment to the end of treatment at 12 weeks]
• Increase in Alpha Diversity and/or Enrichment of Beneficial Bacterial Genera in the Gut Microbiota [Time frame: From baseline to the end of treatment at 12 weeks]
• Achieving a clinically significant reduction in total body weight by at least 3% [Time frame: From baseline to the end of treatment at 12 weeks]

Secondary outcome measures (12)

• A ≥1 stage liver fibrosis improvement with no hepatic steatosis worsening [Time frame: From baseline to the end of treatment at 12 weeks]
• Reduction in the degree of obesity according to Body Mass Index (BMI) [Time frame: From baseline to the end of treatment at 12 weeks]
• Reduction in the degree of obesity according to Body Fat Percentage [Time frame: From baseline to the end of treatment at 12 weeks]
• Reduction in the degree of obesity according to Visceral Fat Level [Time frame: From baseline to the end of treatment at 12 weeks]
• Reduction in the degree of obesity according to Waist Circumference [Time frame: From baseline to the end of treatment at 12 weeks]
• Improvement in total cholesterol levels [Time frame: From baseline to the end of treatment at 12 weeks]
• Improvement in total triglyceride levels [Time frame: From baseline to the end of treatment at 12 weeks]
• Improvement in High-Density Lipoprotein Cholesterol (HDL-C) [Time frame: From baseline to the end of treatment at 12 weeks]
• Improvement in Low-Density Lipoprotein Cholesterol (LDL-C) [Time frame: From baseline to the end of treatment at 12 weeks]
• Improvement in Very Low-Density Lipoprotein Cholesterol (VLDL-C) [Time frame: From baseline to the end of treatment at 12 weeks]
• Improvement in Alanine Aminotransferase (ALT) [Time frame: From baseline to the end of treatment at 12 weeks]
• Improvement in Aspartate Aminotransferase (AST) [Time frame: From baseline to the end of treatment at 12 weeks]

Eligibility criteria

Inclusion criteria

• Mexican mestizo adults of both sexes between 18 to 60 years old
• Diagnosis of MASLD according to the criteria established by the American Association for the Study of Liver Diseases
• Controlled Attenuation Parameter (CAP) score >248 dB/m, liver stiffness <14 kPa according to FibroScan Expert 630 (Echosens, Paris, France)
• Obesity diagnosed by body fat percentage
• Bristol stool scale type 3-4
• Physical inactivity according to the International Physical Activity Questionnaire (IPAQ)
• Alcohol consumption <20 grams/day for women and <30 grams/day for men
• Signed informed consent

Exclusion criteria

• Severe gastrointestinal diseases (e.g., chronic constipation, Crohn's disease, celiac disease, ulcerative colitis, irritable bowel syndrome, diverticulosis, etc.), autoimmune diseases, and malignant neoplasms
• Current or prior 6 weeks consumption of probiotic formulations
• Current or prior 2 months consumption of antibiotics or antiparasitic drugs before the start of the study
• Current consumption of dietary supplements (omega-3 fatty acids, thermogenics, protein, teas, etc.)
• Frequent consumption (greater than or equal to twice a week) of anti-inflammatory drugs, analgesics, or medications that alter normal intestinal function (e.g., laxatives, enemas, antidiarrheal agents, etc.)
• Pregnant women, women planning pregnancy, or breastfeeding women
• Weight loss greater than three kilograms in the last month
• Tobacco consumption
• Allergy or intolerance to cacao, nopal, or crickets
• Previous malabsorptive bariatric surgery (gastric bypass, sleeve gastrectomy), restrictive bariatric surgery (adjustable gastric band), or cosmetic surgical procedures (liposuction, lipo-sculpture, abdominoplasty, etc.) in the last 2 years

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

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

Mexico · 1 center

• Institute of Molecular Biology in Medicine and Gene Therapy — Guadalajara

Publications

• Rosas-Campos R, Sandoval-Rodriguez AS, Rodriguez-Sanabria JS, Vazquez-Esqueda AO, Alfaro-Martinez CR, Escutia-Gutierrez R, Vega-Magana N, Pena-Rodriguez M, Zepeda-Nuno JS, Andrade-Marcial M, Campos-Uscanga Y, Jave-Suarez LF, Santos A, Cerda-Reyes E, Almeida-Lopez M, Martinez-Lopez E, Herrera LA, Armendariz-Borunda J. A Novel Foodstuff Mixture Improves the Gut-Liver Axis in MASLD Mice and the Gut M PMID 38929103
• Rosas-Campos R, Meza-Rios A, Rodriguez-Sanabria JS, la Rosa-Bibiano R, Corona-Cervantes K, Garcia-Mena J, Santos A, Sandoval-Rodriguez A, Armendariz-Borunda J. Dietary supplementation with Mexican foods, Opuntia ficus indica, Theobroma cacao, and Acheta domesticus: Improving obesogenic and microbiota features in obese mice. Front Nutr. 2022 Dec 2;9:987222. doi: 10.3389/fnut.2022.987222. eCollectio PMID 36532548

Identifiers

NCT: NCT07592013 · CI-06624

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗