Fructose Intestinal Gluconeogenesis

NCT ID: NCT07209202

Last Updated: 2025-10-06

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-12-31
• Study Completion Date: 2030-06-30

Brief Summary

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.

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.

Conditions

Healthy Participants; Obese But Otherwise Healthy Participants

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: EXPERIMENTAL

High fructose meal

Intervention Type: OTHER

Liquid meals containing 55% total carbohydrate (16% fructose), 30% fat, 15% protein.

13C labeled fructose, oral

Intervention Type: OTHER

Tracer amount of 13C labeled fructose administered orally in the meals.

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.

Group Type: EXPERIMENTAL

High fructose meal

Intervention Type: OTHER

Liquid meals containing 55% total carbohydrate (16% fructose), 30% fat, 15% protein.

13C labeled fructose, intravenous

Intervention Type: OTHER

Tracer amount of 13C fructose administered intravenously

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.

Group Type: EXPERIMENTAL

Low fructose meal

Intervention Type: OTHER

55% total carbohydrate (6% fructose), 30% fat, 15% protein.

13C labeled fructose, oral

Intervention Type: OTHER

Tracer amount of 13C labeled fructose administered orally in the meals.

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.

Group Type: EXPERIMENTAL

Low fructose meal

Intervention Type: OTHER

55% total carbohydrate (6% fructose), 30% fat, 15% protein.

13C labeled fructose, intravenous

Intervention Type: OTHER

Tracer amount of 13C fructose administered intravenously

Interventions

High fructose meal

Liquid meals containing 55% total carbohydrate (16% fructose), 30% fat, 15% protein.

Intervention Type: OTHER

Low fructose meal

55% total carbohydrate (6% fructose), 30% fat, 15% protein.

Intervention Type: OTHER

13C labeled fructose, oral

Tracer amount of 13C labeled fructose administered orally in the meals.

Intervention Type: OTHER

13C labeled fructose, intravenous

Tracer amount of 13C fructose administered intravenously

Intervention Type: OTHER

Eligibility Criteria

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.

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

Touro University, California

OTHER

Sponsor Role: lead

Responsible Party

Jean-marc Schwarz

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jean-Marc Schwarz, PhD

Role: PRINCIPAL_INVESTIGATOR

Touro University, California

Grace M Jones, PhD

Role: PRINCIPAL_INVESTIGATOR

Touro University, California

Central Contacts

Sally Chiu, PhD

Role: CONTACT

schiu2@touro.edu

707-638-5404

Lisa Johnson, RN

Role: CONTACT

ljohnson19@touro.edu

Other Identifiers

R01DK140477

Identifier Type: NIH

Identifier Source: secondary_id

View Link

M-2624

Identifier Type: -

Identifier Source: org_study_id