Effect of High Protein Diet on Hepatic Steatosis in Patients With MAFLD

Not Applicable

Not yet recruiting

• Conditions: Metabolic Dysfunction Associated Fatty Liver Disease

• Registration Number: NCT06749704
• Lead Sponsor: Institute of Liver and Biliary Sciences, India

Brief Summary

MAFLD is a growing problem in India. Its pathophysiology is complex, but focused on abnormal substrate handling due to mitochondrial dysfunction reflecting as metabolic inflexibility. Nutrition is the cornerstone of management. The ideal macronutrient distribution within a hypocaloric diet is not known yet. Evidence from experimental and a few human studies in obese, highlight the role of dietary proteins, independent of calorie restriction, in reducing hepatic steatosis by improving the cellular and systemic bioenergetics.

Detailed Description

Novelty: First study to assess the effect of high protein diet (HPD) in comparison to a standard protein diet (SPD) within a calorie restricted diet, on both the cellular and systemic bioenergetics in patients with MAFLD.

Objectives: Aims to see the effect of HPD on hepatic steatosis, cellular and systemic bioenergetics, along with metabolic parameters in patients with MAFLD.

Method: In this RCT, patients with MAFLD (n=140) with or without MS, would be randomized into HPD or SPD groups (i.e. 70 in each group), and parameters like hepatic steatosis (CAP by Transient elastography (FibroScan), cellular bioenergetics by oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) as measured using Seahorse Analyzer, and Indirect Calorimetry will be used to assess the fasting and postglucose challenge (Oral glucose tolerance test) REE and RQ. DEXA scan would be used to assess body composition apart from routine blood tests to assess features of Metabolic syndrome. The serum levels of GLP1, CKK, Ghrelin, FGF21, Adipokines like leptin and adiponectin, NADH/NAD ratio, insulin and glucagon would be measured.

Outcome: A HPD is expected to improve hepatic steatosis, blunted fuel switching (RQ) and cellular bioenergetics (OCR) along with metabolic parameters in patients with MAFLD.

Study Timeline

• Status Verified: 2024-05
• Study First Submitted: 2024-05-06
• Study First Submitted QC: 2024-12-24
• Last Update Submitted: 2024-12-24
• Study Start: 2024-12-27
• Study First Posted: 2024-12-27
• Last Update Posted: 2024-12-27
• Primary Completion: 2027-05-01
• Study Completion: 2027-05-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 140

Inclusion Criteria

• Newly diagnosed treatment naïve consenting adults with MAFLD (controlled attenuation parameter; CAP >250, BMI>23 and/or DM) Age 18-65 years

Exclusion Criteria

• • Lean (BMI <23) patients

  • Age <18 and >65 years
  • Individuals who had been hospitalized with complications of Diabetes mellitus, Chronic Kidney disease, Hypertension in the previous 6 months
  • Patients with viral hepatitis
  • Patients with significant alcohol consumption (regular consumption of > 10g per day for females and > 20g/d in males),
  • Patients having chronic inflammatory bowel disease or any chronic and autoimmune diseases will be excluded
  • Pregnant & lactating women

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Assessment of Hepatic steatosis.	3 months	Changes in hepatic steatosis at baseline and follow up would be done using fibro scan (CAP) and Computed Tomography (Liver Attenuation Index).

Secondary Outcome Measures

Name	Time	Method
Assessment of cellular bioenergetics would be done.	3 months	Changes in Extracellular acidification rate(ECAR in mph/min) at baseline and follow up would be done using Seahorse XF analyser.
Assessment of systemic bioenergetics would be done.	3 months	A switch in Respiratory quotient (RQ) at fasting and OGTT would be assessed using indirect calorimetry at baseline and follow up.
Assessment of metabolic markers at baseline and follow up.	3 months	Changes in metabolic markers would be done at baseline and follow up. The following metabolic markers would be assessed :- Blood pressure(systolic and dystolic), HbA1c,Thyroid stimulating hormone , Total lipid profile, CRP levels.
Assessment of muscle mass.	3 months	Assessment of muscle mass would be done by DEXA scan at baseline and follow up.
Assessment of serum levels of FGF21(in ng/ml) and leptin(in ng/ml).	3 months	Assessments would be done using commercially available Elisa kits at baseline and follow up.
Assessment of serum levels of adiponectin(in μg/mL).	3 months	Assessments would be done using commercially available Elisa kits at baseline and follow up.
Assessment of serum levels of insulin(in μU/mL)	3 months	Assessments would be done using commercially available Elisa kits at baseline and follow up.
Assessment of serum levels of glucagon(in pg/mL).	3 months	Assessments would be done using commercially available Elisa kits at baseline and follow up.
Assessment of serum levels of glucagon like peptide(GLP-1) (in pmol/L)	3 months	Assessments would be done using commercially available Elisa kits at baseline and follow up.
Assessment of serum levels of ghrelin (in fmol/ml).	3 months	Assessments would be done using commercially available Elisa kits at baseline and follow up.
Assessment of serum levels of cholecystokinin (in pmol/liter).	3 months	Assessments would be done using commercially available Elisa kits at baseline and follow up.

Trial Locations

Locations (1)

Institute of Liver and Biliary Sciences; 🇮🇳 Delhi, New Delhi, India