Evaluation of Liver and Cardiometabolic Health Benefits on Low Carbohydrate Ketogenic Diet

NCT03141008 | Completed DMC

• 1 other identifier: HM20009338
• Study Type: observational
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

To evaluate the impact of a Low Carbohydrate Ketogenic Diet (LCKD) weight loss program and compare to the standard of care program established for patients with Non-Alcoholic Fatty Liver Disease (NAFLD) on: (1) Liver fat and liver stiffness scores, (2) lipid profile and insulin sensitivity; and (3) depression scores and quality of life, and (4) Cardiometabolic measures such as cardiopulmonary exercise test (CPET) and transthoracic echocardiogram (TTE).

Conditions

Obesity; Fatty Liver; Ketogenic Dieting

Keywords

Ketosis; NAFLD; Obesity

Outcome Measures

Primary Outcomes (1)

• Change in liver fat and stiffness scores compared to control group as well as intrasubject trend

  Performed with a fibroscan

  0, 3, 6, 12 months

Secondary Outcomes (2)

• Change in Cardiometabolic labs

  0, 6, 12 months (3 and 9 months for A1c if >7

• Other specialized testing

  Only to a few of the eligible patients, 0, 3, 12 months

Study Arms (2)

Ketogenic diet exposed group

Fibroscan changes with different diets: Patients in a weight loss program using a ketogenic diet. Will compare differences in Fibroscan and metabolic changes.

Other: Fibroscan changes with different diets

NAFLD diet exposed group

Fibroscan changes with different diets: Patients in a NAFLD clinic using low calorie, low fat diet. Will compare differences in Fibroscan and metabolic changes.

Other: Fibroscan changes with different diets

Interventions

Fibroscan changes with different diets OTHER

Observational study of liver fat and stiffness and cardiometabolic parameters comparing two different standard of care dietary regimens

Ketogenic diet exposed group; NAFLD diet exposed group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

50 people from the PI's weight loss clinic using an a priori ketogenic diet. Will be compared with 50 people from a NAFLD clinic using a low calorie, low fat diet.

You may not qualify if:

• Patients will be excluded if they have known other liver disease such as viral hepatitis, autoimmune hepatitis, liver transplant, severely ill, weekly alcohol use (\>14 drinks in men and \>7 drinks in women), HIV, pregnant females, those\< 18 years, and prisoners.

Sponsors & Collaborators

• Virginia Commonwealth University: lead
• Obesity Treatment Foundation: collaborator

Study Sites (1)

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

Related Publications (12)

• Arulanandan A, Ang B, Bettencourt R, Hooker J, Behling C, Lin GY, Valasek MA, Ix JH, Schnabl B, Sirlin CB, Loomba R. Association Between Quantity of Liver Fat and Cardiovascular Risk in Patients With Nonalcoholic Fatty Liver Disease Independent of Nonalcoholic Steatohepatitis. Clin Gastroenterol Hepatol. 2015 Aug;13(8):1513-20.e1. doi: 10.1016/j.cgh.2015.01.027. Epub 2015 Feb 3.

  PMID: 25661453 BACKGROUND

• Vanwagner LB, Bhave M, Te HS, Feinglass J, Alvarez L, Rinella ME. Patients transplanted for nonalcoholic steatohepatitis are at increased risk for postoperative cardiovascular events. Hepatology. 2012 Nov;56(5):1741-50. doi: 10.1002/hep.25855.

  PMID: 22611040 BACKGROUND

• Francque SM, van der Graaff D, Kwanten WJ. Non-alcoholic fatty liver disease and cardiovascular risk: Pathophysiological mechanisms and implications. J Hepatol. 2016 Aug;65(2):425-43. doi: 10.1016/j.jhep.2016.04.005. Epub 2016 Jun 1.

  PMID: 27091791 BACKGROUND

• Chang Y, Jung HS, Yun KE, Cho J, Cho YK, Ryu S. Cohort study of non-alcoholic fatty liver disease, NAFLD fibrosis score, and the risk of incident diabetes in a Korean population. Am J Gastroenterol. 2013 Dec;108(12):1861-8. doi: 10.1038/ajg.2013.349. Epub 2013 Oct 8.

  PMID: 24100261 BACKGROUND

• Anstee QM, Targher G, Day CP. Progression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis. Nat Rev Gastroenterol Hepatol. 2013 Jun;10(6):330-44. doi: 10.1038/nrgastro.2013.41. Epub 2013 Mar 19.

  PMID: 23507799 BACKGROUND

• Ekstedt M, Hagstrom H, Nasr P, Fredrikson M, Stal P, Kechagias S, Hultcrantz R. Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up. Hepatology. 2015 May;61(5):1547-54. doi: 10.1002/hep.27368. Epub 2015 Mar 23.

  PMID: 25125077 BACKGROUND

• Boursier J, Vergniol J, Guillet A, Hiriart JB, Lannes A, Le Bail B, Michalak S, Chermak F, Bertrais S, Foucher J, Oberti F, Charbonnier M, Fouchard-Hubert I, Rousselet MC, Cales P, de Ledinghen V. Diagnostic accuracy and prognostic significance of blood fibrosis tests and liver stiffness measurement by FibroScan in non-alcoholic fatty liver disease. J Hepatol. 2016 Sep;65(3):570-8. doi: 10.1016/j.jhep.2016.04.023. Epub 2016 May 2.

  PMID: 27151181 BACKGROUND

• Wong RJ, Cheung R, Ahmed A. Nonalcoholic steatohepatitis is the most rapidly growing indication for liver transplantation in patients with hepatocellular carcinoma in the U.S. Hepatology. 2014 Jun;59(6):2188-95. doi: 10.1002/hep.26986. Epub 2014 Apr 25.

  PMID: 24375711 BACKGROUND

• Prati D, Taioli E, Zanella A, Della Torre E, Butelli S, Del Vecchio E, Vianello L, Zanuso F, Mozzi F, Milani S, Conte D, Colombo M, Sirchia G. Updated definitions of healthy ranges for serum alanine aminotransferase levels. Ann Intern Med. 2002 Jul 2;137(1):1-10. doi: 10.7326/0003-4819-137-1-200207020-00006.

  PMID: 12093239 BACKGROUND

• Targher G, Byrne CD, Lonardo A, Zoppini G, Barbui C. Non-alcoholic fatty liver disease and risk of incident cardiovascular disease: A meta-analysis. J Hepatol. 2016 Sep;65(3):589-600. doi: 10.1016/j.jhep.2016.05.013. Epub 2016 May 17.

  PMID: 27212244 BACKGROUND

• Nagano M, Sasaki H, Kumagai S. Association of cardiorespiratory fitness with elevated hepatic enzyme and liver fat in Japanese patients with impaired glucose tolerance and type 2 diabetes mellitus. J Sports Sci Med. 2010 Sep 1;9(3):405-10. eCollection 2010.

  PMID: 24149634 BACKGROUND

• Rinella ME. Nonalcoholic fatty liver disease: a systematic review. JAMA. 2015 Jun 9;313(22):2263-73. doi: 10.1001/jama.2015.5370.

  PMID: 26057287 RESULT

Biospecimen

Retention: SAMPLES WITHOUT DNA

routine care labs will be done on patients including Comprehensive metabolic panel, A1c, lipids and insulin levels. Additional specimens will be taken for serum, urine, stool and saliva. These will be collected at time points 0, (additional timepoint of 1 month for saliva, stool and urine), 3 months, 6 months and 12 months.

MeSH Terms

Conditions

Obesity; Fatty Liver; Ketosis; Non-alcoholic Fatty Liver Disease

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Liver Diseases; Digestive System Diseases; Acidosis; Acid-Base Imbalance; Metabolic Diseases

Study Officials

• Susan Wolver, MD

  VCU

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2017
• First Posted: May 4, 2017
• Study Start: September 15, 2017
• Primary Completion: February 27, 2020
• Study Completion: February 27, 2020
• Last Updated: March 10, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)