De Novo Lipogenesis, Lipid and Carbohydrate Metabolism in Non-alcoholic Fatty Liver Disease

NCT00714129 | Completed

• 3 other identifiers: R01DK078133-01NIH R01DK078133-01A1ADA 1-08-CR-56
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

The worldwide epidemic of obesity is paralleled with increased cases of non-alcoholic liver disease (liver fat accumulation) and diabetes. Fat belongs in the adipose tissue, and if excess fat accumulates in the liver or muscle, these tissues cannot use sugar efficiently. It has been discovered that when large quantities of fructose (a sugar present in soft drinks) are consumed, the conversion of carbohydrate (CHO) to fat in the liver increases. We hypothesize that: 1) subjects with fatty liver have a higher CHO uptake and conversion to fat in their liver when compared to matched control subjects with normal liver fat content; and that: 2) when subjects with fatty liver are fed a diet limiting fructose and simple sugars will decrease their liver CHO fat content. This reduction in liver fat will normalize the way the liver responds to sugar and insulin, reversing the pre-diabetic state. The measurement of these parameters will be done using state-of-the-art techniques such as safe non-radioactive isotope tracers and non-invasive magnetic resonance spectroscopy. For more information, please call 415-206-5532 for a phone screening

Conditions

Non-alcoholic Fatty Liver Disease; Diabetes

Keywords

Steatosis; Diabetes

Outcome Measures

Primary Outcomes (1)

• Stable isotopic and magnetic resonance measures to determine the changes in lipid and carbohydrate metabolism after dietary intervention

  approximately 8 weeks

Secondary Outcomes (1)

• DEXA, insulin sensitivity and energy expenditure changes due to dietary intervention

  8 weeks

Study Arms (2)

1

EXPERIMENTAL

Weight loss diet - normal diet

Other: Dietary intervention (calorie restricted diet)

2

EXPERIMENTAL

Weight loss diet - low in simple sugars (specifically fructose)

Other: Dietary intervention (calorie restricted diet)

Interventions

Dietary intervention (calorie restricted diet) OTHER

Participants in Aim 2 will receive a calorie restricted diet. This group will receive all their food for approximately 8 weeks which is the similar composition of their current diet.

1

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• In the steatotic subjects, steatosis will be diagnosed by MRS or liver biopsy in which \>33% of the hepatocytes will contain fat. Non-steatotic controls will not have biopsies since they are not medically warranted; thus, to ensure they do not have steatosis they will undergo MRS during screening and have a total lipid: unsuppressed water \< 0.05.

You may not qualify if:

• Habitual consumption of alcohol \> 20 g/day for men and 10 g/day for women
• Confirmed HIV-1 infection, Hgb \<13 g/dL for males and \<12 g/dL for females
• Abnormal hepatitis B or C serology
• Diabetes or current use of any antidiabetic or hypolipidemic agents
• Presence of metal-containing substances in the body (e.g. a fragment in the eye, aneurysm clips, ear implants, spinal nerve stimulators or a pacemaker)
• Weight over 350 pounds or severe claustrophobia, which would preclude the MR studies
• Any condition that would preclude adherence to the protocol or the ability to provide informed consent
• Change in body weight \>5% within the preceding 6 months (by self-report)
• Known intolerance, allergy or hypersensitivity to fructose
• Pregnancy or lactation (for women); OR
• Any other condition that, in the opinion of the investigators, would put the subject at risk.

Sponsors & Collaborators

• University of California, San Francisco: lead
• Touro University: collaborator
• American Diabetes Association: collaborator

Study Sites (1)

Touro University

Vallejo, California, 94592, United States

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Diabetes Mellitus; Fatty Liver

Interventions

Diet Therapy; Caloric Restriction

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Nutrition Therapy; Therapeutics; Energy Intake; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Study Officials

• Jean-Marc Schwarz, PhD

  Touro University and UCSF

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2008
• First Posted: July 14, 2008
• Study Start: September 1, 2007
• Primary Completion: October 12, 2012
• Study Completion: October 12, 2012
• Last Updated: February 17, 2020

Record last verified: 2020-02

Locations

US (1)