Fructose Intestinal Gluconeogenesis (FIG)

Fructose Metabolism Effects on the Liver: Unraveling the Role of Defective Intestinal GNG in Individuals With Obesity

This study will test the hypothesis that within a defined range of fructose intake, the ability to convert fructose to glucose (via gluconeogenesis) in the small intestine plays a protective role for the liver, shielding it from the deleterious effects of fructose. We will investigate whether this protective effect of the intestine is impaired in individuals with obesity.

Study Overview

• Status: Recruiting
• Conditions: Healthy Participants; Obese But Otherwise Healthy Participants
• Intervention / Treatment: Other: High fructose meal; Other: 13C labeled fructose, oral; Other: 13C labeled fructose, intravenous; Other: Low fructose meal

Detailed Description

Qualified participants will undergo a sugar tolerance test at baseline and then randomized to undergo four separate outpatient tracer/feeding studies in a crossover fashion. After an overnight fast, a six-hour fed tracer study will be initiated, during which participants will consume liquid meals containing stable isotopes at regular intervals and receive other isotopes intravenously. Meal composition will differ only by fructose content (High vs. Low) and tracer (oral vs. intravenous 13C-labeled fructose). Blood and urine samples will be collected frequently throughout the study. Each visit will be performed approximately three weeks apart. Vital signs and anthropometrics will be measured at each clinic visit.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sally Chiu, PhD; Phone Number: 707-638-5404; Email: schiu2@touro.edu
• Study Contact Backup: Name: Lisa Johnson, RN; Email: ljohnson19@touro.edu

Study Locations

• United States
  • California
    • Vallejo, California, United States, 95492
      • Recruiting
      • Touro University California
      • Contact: Sally Chiu, PhD; Email: schiu2@touro.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• BMI 30 to 38 kg/m2 (obese group) or BMI 19 to 25 kg/m2 (lean group)

Exclusion Criteria:

• Pregnancy or lactation within the past six months;
• Type 1 or 2 diabetes mellitus (including fasting glucose ≥126 mg/dL, HgbA1c ≥6.5%);
• History of liver disease or AST and ALT 2x above the upper limit of normal;
• Fasting triglyceride > 300 mg/dl; total cholesterol levels above the 95th percentile for age and sex;
• Hemoglobin (Hgb) <12.5g/d or hematocrit<3x Hgb value;
• Report of HIV or hepatitis B or C infection;
• History of cancer, other than basal cell or squamous cell carcinoma or kidney disease stage 3 or higher or patients currently on dialysis;
• Use of any anti-diabetic medications or hypolipidemic agents in the past six months;
• History of surgical procedure for obesity;
• Change in body weight >5% in the past six months (by self-report);
• History of other conditions known to affect insulin sensitivity and lipid metabolism (e.g., polycystic ovary syndrome), history of galactosemia, hereditary fructose intolerance, or who test positive for fructose malabsorption at screening;
• Known intolerance to acetaminophen.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High fructose meals, oral 13C fructose; Liquid meals will be fed, containing 55% total carbohydrate (16% fructose), 30% fat, 15% protein, and a tracer amount of 13C fructose.	Other: High fructose meal; Liquid meals containing 55% total carbohydrate (16% fructose), 30% fat, 15% protein.; Other: 13C labeled fructose, oral; Tracer amount of 13C labeled fructose administered orally in the meals.
Experimental: High Fructose Meals, IV 13C Fructose; Liquid meals will be fed, containing 55% total carbohydrate (16% fructose), 30% fat, 15% protein. A tracer amount of 13C fructose will be administered intravenously.	Other: High fructose meal; Liquid meals containing 55% total carbohydrate (16% fructose), 30% fat, 15% protein.; Other: 13C labeled fructose, intravenous; Tracer amount of 13C fructose administered intravenously
Experimental: Low fructose meals, oral fructose tracer; Liquid meals will be fed, containing 55% total carbohydrate (6% fructose), 30% fat, 15% protein, and a tracer amount of 13C fructose.	Other: 13C labeled fructose, oral; Tracer amount of 13C labeled fructose administered orally in the meals.; Other: Low fructose meal; 55% total carbohydrate (6% fructose), 30% fat, 15% protein.
Experimental: Low fructose meals, IV 13C fructose tracer; Liquid meals will be fed, containing 55% total carbohydrate (6% fructose), 30% fat, 15% protein. A tracer amount of 13C fructose will be administered intravenously.	Other: 13C labeled fructose, intravenous; Tracer amount of 13C fructose administered intravenously; Other: Low fructose meal; 55% total carbohydrate (6% fructose), 30% fat, 15% protein.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fru-GNG	Total amount of fructose converted to glucose	6 hours
Fru-hGNG	Amount of fructose converted to glucose in the liver	6 hours
Fru-iGNG	Amount of fructose converted to glucose in the intestine	6 hours
De novo lipogenesis (DNL)	Percent of newly synthesized palmitate	6 hours

Collaborators and Investigators

• Sponsor: Touro University, California
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Grace M Jones, PhD, Touro University, California; Principal Investigator: Jean-Marc Schwarz, PhD, Touro University, California

Study record dates

Study Major Dates

• Study Start (Actual): March 2, 2026
• Primary Completion (Estimated): June 1, 2030
• Study Completion (Estimated): June 1, 2030

Study Registration Dates

• First Submitted: September 30, 2025
• First Submitted That Met QC Criteria: September 30, 2025
• First Posted (Actual): October 6, 2025

Study Record Updates

• Last Update Posted (Actual): March 6, 2026
• Last Update Submitted That Met QC Criteria: March 4, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Fructose; Sugar
• Other Study ID Numbers: M-2624; R01DK140477 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The de-identified clinical and laboratory data set will be made available upon request to academic investigators.
• IPD Sharing Time Frame: Study data will be made available for at least 5 years from publication of the primary manuscript.
• IPD Sharing Access Criteria: Academic investigators may request data and supporting information upon request to the PI.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No