Measuring Amino Acid and Glucose Metabolism in Healthy Volunteers and NAFLD Patients Using Total-body PET

Quantification of Amino Acid and Glucose Metabolism in Healthy Controls and Patients With Non-alcoholic Fatty Liver Disease Using Total- Body PET

This observational study aims to quantify whole-body amino acid and glucose metabolism in healthy adults and in patients with non-alcoholic fatty liver disease (NAFLD) using total-body PET/CT. The study investigates how orally and intravenously administered PET tracers (18F-FDG and 18F-FET) are absorbed in the gastrointestinal tract, distributed across major organs, and metabolized in different physiological and pathological states. A further objective is to examine how glucagon, during a pancreatic clamp using somatostatin, influences amino acid metabolism in healthy individuals and whether this response is altered in patients with NAFLD.

Participants will be healthy volunteers or patients with NAFLD, aged 18-70 years. Depending on study group, participants will undergo one or more total-body PET/CT scans following oral or intravenous tracer administration, and in some cases receive glucagon or placebo infusion. Blood samples will be collected during scanning to assess hormone levels and metabolic responses. Data from these imaging sessions will be used to characterize nutrient metabolism, compare oral and intravenous tracer kinetics, and explore glucagon-induced metabolic changes across study groups.

Study Overview

• Status: Active, not recruiting
• Conditions: Glucose Metabolism; NAFLD (Nonalcoholic Fatty Liver Disease)
• Intervention / Treatment: Drug: 18F-FDG (oral); Drug: 18F-FDG (intravenous); Other: Oral Glucose Tolerance Test; Drug: 18F-FET (oral); Drug: 18F-FET (intravenous); Drug: Glucagon; Drug: Somatostatin; Drug: Sodium chloride (placebo)

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • Copenhagen University Hospital - Rigshospitalet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 18-70 years
• Body mass index (BMI) 20-27 kg/m2

Exclusion Criteria:

• Pregnancy
• Claustrophobia
• Inability to give consent due to psychological or other causes
• Inability to speak/read Danish
• Diabetes, cancer (active or treated within the last five years) or inflammatory diseases.
• Low albumin
• Chronic disorders that require medical treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Healthy Controls: FDG (oral & IV); Healthy volunteers receive 18F-FDG by oral administration and intravenous administration on separate study days, including an oral glucose tolerance test visit. Total-body PET/CT imaging is performed after each tracer administration.	Drug: 18F-FDG (oral); Oral administration of 18F-fluorodeoxyglucose (^18F-FDG) for total-body PET/CT to assess gastrointestinal absorption, systemic biodistribution, and whole-body glucose metabolism.; Drug: 18F-FDG (intravenous); Intravenous bolus administration of 18F-fluorodeoxyglucose (18F-FDG) for total-body PET/CT to measure systemic biodistribution and whole-body glucose metabolism.; Other: Oral Glucose Tolerance Test; Standard oral glucose load (75 g in 250 mL water) to assess glucose-stimulated metabolic responses during PET/CT.
Experimental: Healthy Controls: FET (oral & IV); Healthy volunteers receive 18F-FET by oral administration and intravenous administration on separate study days. Dynamic and static total-body PET/CT imaging is performed.	Drug: 18F-FET (oral); Oral administration of O-(2-[18F]fluoroethyl)-L-tyrosine (18F-FET) for total-body PET/CT to assess gastrointestinal amino acid absorption and whole-body amino acid metabolism.; Drug: 18F-FET (intravenous); Intravenous bolus administration of O-(2-[18F]fluoroethyl)-L-tyrosine (18F-FET) for total-body PET/CT to measure systemic amino acid biodistribution and dynamic metabolic kinetics.
Experimental: Healthy Controls: Oral FET + Glucagon/Somatostatin Clamp (Crossover); Healthy participants undergo two study days with oral ^18F-FET administration combined with either glucagon infusion during a pancreatic clamp (somatostatin infusion) or placebo. Total-body PET/CT imaging is performed using a crossover design.	Drug: 18F-FET (oral); Oral administration of O-(2-[18F]fluoroethyl)-L-tyrosine (18F-FET) for total-body PET/CT to assess gastrointestinal amino acid absorption and whole-body amino acid metabolism.; Drug: Glucagon; Continuous intravenous glucagon infusion to stimulate hepatic amino acid metabolism during a pancreatic clamp.; Drug: Somatostatin; Continuous intravenous somatostatin infusion to suppress endogenous pancreatic hormone secretion during the pancreatic clamp.; Drug: Sodium chloride (placebo); Intravenous infusion of isotonic sodium chloride solution used as placebo during crossover comparison with glucagon infusion.
Experimental: NAFLD Patients: Oral FET + Glucagon/Somatostatin Clamp (Crossover); Participants with NAFLD undergo two study days with oral ^18F-FET administration combined with either glucagon infusion during a pancreatic clamp (somatostatin infusion) or placebo. Total-body PET/CT imaging is performed using a crossover design.	Drug: 18F-FET (oral); Oral administration of O-(2-[18F]fluoroethyl)-L-tyrosine (18F-FET) for total-body PET/CT to assess gastrointestinal amino acid absorption and whole-body amino acid metabolism.; Drug: Glucagon; Continuous intravenous glucagon infusion to stimulate hepatic amino acid metabolism during a pancreatic clamp.; Drug: Somatostatin; Continuous intravenous somatostatin infusion to suppress endogenous pancreatic hormone secretion during the pancreatic clamp.; Drug: Sodium chloride (placebo); Intravenous infusion of isotonic sodium chloride solution used as placebo during crossover comparison with glucagon infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Whole-body tracer uptake (SUVmean) assessed using total-body PET/CT	0-180 minutes after tracer administration

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark

Study record dates

Study Major Dates

• Study Start (Actual): November 5, 2024
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2027

Study Registration Dates

• First Submitted: January 16, 2026
• First Submitted That Met QC Criteria: January 16, 2026
• First Posted (Actual): January 26, 2026

Study Record Updates

• Last Update Posted (Actual): February 2, 2026
• Last Update Submitted That Met QC Criteria: January 29, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Hypothalamic Hormones; Peptide Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Nerve Tissue Proteins; Proteins; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Carbohydrates; Inorganic Chemicals; Chlorine Compounds; Deoxyglucose; Deoxy Sugars; Pancreatic Hormones; Sodium Compounds; Blood Chemical Analysis; Clinical Chemistry Tests; Proglucagon; Pituitary Hormone Release Inhibiting Hormones; Diagnostic Techniques, Endocrine; Chlorides; Hydrochloric Acid; Fluorodeoxyglucose F18; Glucagon; Somatostatin; Sodium Chloride; Glucose Tolerance Test; (18F)fluoroethyltyrosine
• Other Study ID Numbers: 565_23

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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