Effect of VLCD on the Reduction of Liver Steatosis and Fibrosis in Subjects With Obesity and NAFLD

NCT04861571 | Active Not Recruiting DMC

• 1 other identifier: 202008444
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Non-alcoholic fatty liver disease (NAFLD) is a common complication of obesity which can progress to deadly complications like end-stage liver disease and hepatocellular carcinoma. In the wake of the obesity epidemic, NAFLD is becoming the main etiology of liver transplantation in the US. Currently, there are no FDA approved pharmacological treatments for NAFLD. Weight loss through lifestyle modifications, pharmacotherapy and bariatric surgery can be effective strategies for the management of NAFLD. Even though substantial weight loss and improvement in NAFLD can be achieved with bariatric surgery, only a small proportion of patients with obesity undergo surgery. Very-low calorie diets (VLCD) are replacement meals manufactured to substitute natural foods and limited total intake of 800-960 kcal in divided meals. Very low-calorie diets can produce substantial weight loss of 10% over 2 to 3 months. We hypothesize that VLCD reduce liver steatosis and, fibrosis measured non-invasively with transient elastography. Our main aim is #1 to assess the effect of VLCD on liver fatty infiltration and fibrosis. We also have three exploratory aims exploring novel pathogenic factors that mediate the improvement of NAFLD by VLCD: #2 assess the effect of VLCD on micro RNAs (miRs) associated with pathophysiology of NAFLD: #3 assess the effect of VLCD on changes of salivary and fecal microbiome in the setting of NAFLD: #4 to determine the effect of VLCD on platelet function. This pilot project will produce preliminary data for the development of a larger grant application to study the efficacy of VLCD in the management of NAFLD. Furthermore, it will potentially identify factors that mediate improvement of NAFLD after VLCD. We will treat 10 subjects with obesity and NAFLD for 8 weeks with VLCD or lower calorie diet (control group) and obtain transient elastography before and after the interventions along with other measurements of interest. Our project may have significant impact by establishing VLCD as a clinically effective option for the improvement of liver steatosis and fibrosis in patients with obesity and NAFLD ineligible or without access to bariatric surgery.

Conditions

NAFLD

Outcome Measures

Primary Outcomes (2)

• Liver steatosis

  The investigators will assess the effect of VLCD on liver steatosis using transient elastography. The elastography parameter of interest is the controlled attenuation parameter (CAP) reported as a continuous variable in decibel per meter (dB/m).

  8 weeks

• Liver fibrosis

  The investigators will assess the effect of VLCD on liver fibrosis using transient elastography. The elastography parameter of interest is the liver stiffness measurement (LFM) reported as a continuous variable in kilopascal (kPa).

  8 weeks

Secondary Outcomes (4)

• Micro RNA (miRNA)

  8 weeks

• Fecal microbiome

  8 weeks

• Salivary microbiome

  8 weeks

• Platelet function

  8 weeks

Study Arms (2)

Very Low Calorie Diet Arm

EXPERIMENTAL

We plan to perform a controlled, non-randomized, open-label, pilot clinical trial to evaluate the effect of an 8-week VLCD intervention on NAFLD.

Dietary Supplement: Dietary intervention with very low calorie diet (VLCD)

Control Arm

OTHER

The control group will consume a lower calorie diet and will be instructed to reduce their usual intake of normally consumed foods by up to 500 kcal per day but no less than 1200 kcal per day.

Other: Control Arm

Interventions

Dietary intervention with very low calorie diet (VLCD) DIETARY_SUPPLEMENT

The VLCD program will last 8 weeks. The only sources of nutrition during this phase are the Optifast® products providing up to 800 kcal per day. Two liters (67.63 fl oz) of water should also be consumed each day. Participants will be instructed to use 5 replacement meals per day (800 kcal total) with 40% of calories as protein, 40% as carbohydrate, and 20% as fat.

Also known as: VLCD Arm

Very Low Calorie Diet Arm

Control Arm OTHER

The control group will consume a lower calorie diet and will be instructed to reduce their usual intake of normally consumed foods by up to 500 kcal per day but no less than 1200 kcal per day.

Control Arm

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Male and female subjects with age ≥ 18 years old and \< 70 years old.
• BMI ≥ 30 kg/m2 and ≤ 50 kg/m2
• Negative tests for viral hepatitis C (hepatitis C antibody) and autoimmune hepatitis (anti-smooth muscle antibody)
• Evidence of liver steatosis on an image method such as ultrasound, CT scan or MRI, or subjects with elastography score F1 and above and/or S1 and above can be included
• Type 1 diabetes mellitus
• Subjects with type 2 diabetes mellitus who use insulin
• Heart failure
• Myocardial infarction within last 6 months
• Unstable angina
• Chronic kidney disease with eGFR ≤ 30 mL/min/1.73 m²
• Chronic obstructive pulmonary disease requiring O2 supplementation
• Coexisting liver disease or end-stage liver disease
• Severe or uncontrolled mental health disease, including eating disorders
• Gout
• History of uric acid nephrolithiasis

Sponsors & Collaborators

• University of Iowa: lead

Study Sites (1)

University of Iowa Health Care

Iowa City, Iowa, 52242, United States

Location

Related Publications (7)

• Acharya C, Sahingur SE, Bajaj JS. Microbiota, cirrhosis, and the emerging oral-gut-liver axis. JCI Insight. 2017 Oct 5;2(19):e94416. doi: 10.1172/jci.insight.94416.

  PMID: 28978799 BACKGROUND

• Ard JD, Lewis KH, Rothberg A, Auriemma A, Coburn SL, Cohen SS, Loper J, Matarese L, Pories WJ, Periman S. Effectiveness of a Total Meal Replacement Program (OPTIFAST Program) on Weight Loss: Results from the OPTIWIN Study. Obesity (Silver Spring). 2019 Jan;27(1):22-29. doi: 10.1002/oby.22303. Epub 2018 Nov 13.

  PMID: 30421863 BACKGROUND

• Bajaj JS, Betrapally NS, Hylemon PB, Heuman DM, Daita K, White MB, Unser A, Thacker LR, Sanyal AJ, Kang DJ, Sikaroodi M, Gillevet PM. Salivary microbiota reflects changes in gut microbiota in cirrhosis with hepatic encephalopathy. Hepatology. 2015 Oct;62(4):1260-71. doi: 10.1002/hep.27819. Epub 2015 May 6.

  PMID: 25820757 BACKGROUND

• Gjorgjieva M, Sobolewski C, Dolicka D, Correia de Sousa M, Foti M. miRNAs and NAFLD: from pathophysiology to therapy. Gut. 2019 Nov;68(11):2065-2079. doi: 10.1136/gutjnl-2018-318146. Epub 2019 Jul 12.

  PMID: 31300518 BACKGROUND

• Lin WY, Wu CH, Chu NF, Chang CJ. Efficacy and safety of very-low-calorie diet in Taiwanese: a multicenter randomized, controlled trial. Nutrition. 2009 Nov-Dec;25(11-12):1129-36. doi: 10.1016/j.nut.2009.02.008. Epub 2009 Jul 9.

  PMID: 19592223 BACKGROUND

• Mikolasevic I, Orlic L, Franjic N, Hauser G, Stimac D, Milic S. Transient elastography (FibroScan((R))) with controlled attenuation parameter in the assessment of liver steatosis and fibrosis in patients with nonalcoholic fatty liver disease - Where do we stand? World J Gastroenterol. 2016 Aug 28;22(32):7236-51. doi: 10.3748/wjg.v22.i32.7236.

  PMID: 27621571 BACKGROUND

• Anfossi G, Russo I, Trovati M. Platelet dysfunction in central obesity. Nutr Metab Cardiovasc Dis. 2009 Jul;19(6):440-9. doi: 10.1016/j.numecd.2009.01.006. Epub 2009 Apr 5.

  PMID: 19346117 BACKGROUND

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

Diet Therapy

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Nutrition Therapy; Therapeutics

Study Officials

• Marcelo L Correia, MD PhD

  University of Iowa

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD Clinical Assistant Professor

Study Record Dates

• First Submitted: April 21, 2021
• First Posted: April 27, 2021
• Study Start: October 1, 2023
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: March 10, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)