Clinical trial NCT06676813: Effect of Alternate Day Fasting Over Standard Medical Management Alone to Reverse Non-alcoholic Steatohepatitis.
Official title: Effect of Alternate Day Fasting Over Standard Medical Management Alone to Reverse Non-alcoholic Steatohepatitis(NASH), A Randomized Controlled Trial. FAST Trial"
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Non Alcoholic Steatohepatitis
Keywords: Alternate day fasting.
NASH
MASH
Steatotic liver disease
Cirrhosis
Lead sponsor: Institute of Liver and Biliary Sciences, India
Sponsor class: OTHER
First posted: 2024-11-06
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomised controlled trial.
Primary purpose: TREATMENT

Brief summary: The aims of this study are as follows: To compare the role of alternate-day fasting over standard medical management alone to reverse NASH.

Detailed description: Emerging evidence suggests the role of alternate-day fasting (ADF) in patients with obesity and fatty liver. It helps to lose weight and improvement in liver fat content. ADF regimen protocol includes fast day(restricted calorie intake and time-specific feeding) and feast day(ad libitum feed over 24 hours). Lowering the weight and improvement of the fatty liver. NASH is a prevalent cause of liver disease. Literature is evident that ADF improves fatty liver and metabolic components, and NASH improves with weight loss. Still, data about the role of ADF in the management of NASH is lacking. Hence, this study focuses on the role of ADF in NASH.

Eligibility criteria: Inclusion Criteria:

* Age 18-65 years. BMI 25-40kg/m3, and CAP more than 290
* Stable weight in the last 3 months prior to enrolling in the study(\<5kg weight variation)
* Imaging showed steatotic liver disease, liver stiffness \<14kPa measured by fibroscan
* Histologically proven NASH/MASH, fibrosis up to F3
* Subjects willing to participate in the study

Exclusion Criter

* Liver stiffness \>14kPa measured by fibroscan or Fibrosis \>F3
* Diabetes with HbA1c\>8.5%
* Patients with another co-existing active liver disease e.g. hepatitis B or C, alcoholic liver disease
* Patients with cirrhosis, hepatocellular carcinoma(HCC), or other malignancy
* Chronic kidney disease, cardiovascular disorders, uncontrolled hypertension
* Chronic infections, chronic inflammatory diseases
* Patients on weight loss medications e.g semaglutide
* Pregnant or lactating women and those planning a pregnancy A patient who is not willing to participate in the study or failed to provide the consent

Primary outcomes:
measure: Change of NASH over a 24-week duration.
timeFrame: 24 weeks
Secondary outcomes:
measure: Change in the quality of life index
timeFrame: Change from baseline to 24 weeks
measure: Change in stage of fibrosis
timeFrame: Change from baseline to 24 weeks
measure: Weight
timeFrame: Change from baseline to 24 weeks
measure: Change in glycaemic status
timeFrame: Change from baseline to 24 weeks
measure: Change in liver fat content
timeFrame: Change from baseline to 24 weeks
measure: Change in bone mineral density
timeFrame: Change from baseline to 24 weeks
measure: Change in faecal microbiota.
timeFrame: Change from baseline to 24 weeks
measure: Body mass index
timeFrame: 24 weeks
measure: Waist to hip ratio
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Delhi
country: India
facility: Institute of Liver and Biliary Sciences
Study officials:
References:
citation: Teng ML, Ng CH, Huang DQ, Chan KE, Tan DJ, Lim WH, Yang JD, Tan E, Muthiah MD. Global incidence and prevalence of nonalcoholic fatty liver disease. Clin Mol Hepatol. 2023 Feb;29(Suppl):S32-S42. doi: 10.3350/cmh.2022.0365. Epub 2022 Dec 14.
citation: Carr RM, Oranu A, Khungar V. Nonalcoholic Fatty Liver Disease: Pathophysiology and Management. Gastroenterol Clin North Am. 2016 Dec;45(4):639-652. doi: 10.1016/j.gtc.2016.07.003. Epub 2016 Oct 13.
citation: Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, Charlton M, Sanyal AJ. The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology. 2012 Jun;55(6):2005-23. doi: 10.1002/hep.25762. No abstract available.
citation: Rinella ME, Lazarus JV, Ratziu V, Francque SM, Sanyal AJ, Kanwal F, Romero D, Abdelmalek MF, Anstee QM, Arab JP, Arrese M, Bataller R, Beuers U, Boursier J, Bugianesi E, Byrne CD, Castro Narro GE, Chowdhury A, Cortez-Pinto H, Cryer DR, Cusi K, El-Kassas M, Klein S, Eskridge W, Fan J, Gawrieh S, Guy CD, Harrison SA, Kim SU, Koot BG, Korenjak M, Kowdley KV, Lacaille F, Loomba R, Mitchell-Thain R, Morgan TR, Powell EE, Roden M, Romero-Gomez M, Silva M, Singh SP, Sookoian SC, Spearman CW, Tiniakos D, Valenti L, Vos MB, Wong VW, Xanthakos S, Yilmaz Y, Younossi Z, Hobbs A, Villota-Rivas M, Newsome PN; NAFLD Nomenclature consensus group. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. Hepatology. 2023 Dec 1;78(6):1966-1986. doi: 10.1097/HEP.0000000000000520. Epub 2023 Jun 24.
citation: Loomba R, Wong R, Fraysse J, Shreay S, Li S, Harrison S, Gordon SC. Nonalcoholic fatty liver disease progression rates to cirrhosis and progression of cirrhosis to decompensation and mortality: a real world analysis of Medicare data. Aliment Pharmacol Ther. 2020 Jun;51(11):1149-1159. doi: 10.1111/apt.15679. Epub 2020 May 5.
citation: Rinella ME, Neuschwander-Tetri BA, Siddiqui MS, Abdelmalek MF, Caldwell S, Barb D, Kleiner DE, Loomba R. AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology. 2023 May 1;77(5):1797-1835. doi: 10.1097/HEP.0000000000000323. Epub 2023 Mar 17. No abstract available.
citation: Sanyal AJ, Chalasani N, Kowdley KV, McCullough A, Diehl AM, Bass NM, Neuschwander-Tetri BA, Lavine JE, Tonascia J, Unalp A, Van Natta M, Clark J, Brunt EM, Kleiner DE, Hoofnagle JH, Robuck PR; NASH CRN. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med. 2010 May 6;362(18):1675-85. doi: 10.1056/NEJMoa0907929. Epub 2010 Apr 28.
citation: Promrat K, Kleiner DE, Niemeier HM, Jackvony E, Kearns M, Wands JR, Fava JL, Wing RR. Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis. Hepatology. 2010 Jan;51(1):121-9. doi: 10.1002/hep.23276.
citation: van den Hoek AM, de Jong JCBC, Worms N, van Nieuwkoop A, Voskuilen M, Menke AL, Lek S, Caspers MPM, Verschuren L, Kleemann R. Diet and exercise reduce pre-existing NASH and fibrosis and have additional beneficial effects on the vasculature, adipose tissue and skeletal muscle via organ-crosstalk. Metabolism. 2021 Nov;124:154873. doi: 10.1016/j.metabol.2021.154873. Epub 2021 Sep 1.
citation: Sullivan S, Kirk EP, Mittendorfer B, Patterson BW, Klein S. Randomized trial of exercise effect on intrahepatic triglyceride content and lipid kinetics in nonalcoholic fatty liver disease. Hepatology. 2012 Jun;55(6):1738-45. doi: 10.1002/hep.25548. Epub 2012 Apr 25.
citation: Yang W, Cao M, Mao X, Wei X, Li X, Chen G, Zhang J, Wang Z, Shi J, Huang H, Yao X, Liu C. Alternate-day fasting protects the livers of mice against high-fat diet-induced inflammation associated with the suppression of Toll-like receptor 4/nuclear factor kappaB signaling. Nutr Res. 2016 Jun;36(6):586-93. doi: 10.1016/j.nutres.2016.02.001. Epub 2016 Feb 16.
citation: Wei X, Lin B, Huang Y, Yang S, Huang C, Shi L, Liu D, Zhang P, Lin J, Xu B, Guo D, Li C, He H, Liu S, Xue Y, Xu Y, Zhang H. Effects of Time-Restricted Eating on Nonalcoholic Fatty Liver Disease: The TREATY-FLD Randomized Clinical Trial. JAMA Netw Open. 2023 Mar 1;6(3):e233513. doi: 10.1001/jamanetworkopen.2023.3513.
citation: Cai H, Qin YL, Shi ZY, Chen JH, Zeng MJ, Zhou W, Chen RQ, Chen ZY. Effects of alternate-day fasting on body weight and dyslipidaemia in patients with non-alcoholic fatty liver disease: a randomised controlled trial. BMC Gastroenterol. 2019 Dec 18;19(1):219. doi: 10.1186/s12876-019-1132-8.
citation: Hatori M, Vollmers C, Zarrinpar A, DiTacchio L, Bushong EA, Gill S, Leblanc M, Chaix A, Joens M, Fitzpatrick JA, Ellisman MH, Panda S. Time-restricted feeding without reducing caloric intake prevents metabolic diseases in mice fed a high-fat diet. Cell Metab. 2012 Jun 6;15(6):848-60. doi: 10.1016/j.cmet.2012.04.019. Epub 2012 May 17.