Clinical trial NCT06749704: Effect of High Protein Diet on Hepatic Steatosis in Patients With MAFLD
Official title: Effect of High Protein Diet on Hepatic Steatosis, Inflammation and Mitochondrial Bioenergetics in Patients With MAFLD : A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Metabolic Dysfunction Associated Fatty Liver Disease
Keywords: mitochondrial dysfunction
metabolic inflexibility
FGF21 resistance
Lead sponsor: Institute of Liver and Biliary Sciences, India
Sponsor class: OTHER
First posted: 2024-12-27
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Open Label
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Assessment of Hepatic steatosis.
timeFrame: 3 months
Secondary outcomes:
measure: Assessment of cellular bioenergetics would be done.
timeFrame: 3 months
measure: Assessment of cellular bioenergetics would be done.
timeFrame: 3 months
measure: Assessment of systemic bioenergetics would be done.
timeFrame: 3 months
measure: Assessment of metabolic markers at baseline and follow up.
timeFrame: 3 months
measure: Assessment of muscle mass.
timeFrame: 3 months
measure: Assessment of serum levels of FGF21(in ng/ml) and leptin(in ng/ml).
timeFrame: 3 months
measure: Assessment of serum levels of adiponectin(in μg/mL).
timeFrame: 3 months
measure: Assessment of serum levels of insulin(in μU/mL)
timeFrame: 3 months
measure: Assessment of serum levels of glucagon(in pg/mL).
timeFrame: 3 months
measure: Assessment of serum levels of glucagon like peptide(GLP-1) (in pmol/L)
timeFrame: 3 months
measure: Assessment of serum levels of ghrelin (in fmol/ml).
timeFrame: 3 months
measure: Assessment of serum levels of cholecystokinin (in pmol/liter).
timeFrame: 3 months
Other outcomes:
Locations:
city: Delhi
country: India
facility: Institute of Liver and Biliary Sciences
state: New Delhi
Study officials:
affiliation: Institute of Liver and Biliary Sciences
name: Jaya Benjamin, PhD
role: STUDY_DIRECTOR
References: