Metabolic Flux Analysis in Metabolic Dysfunction-Associated Steatotic Liver Disease

Trial statusNot yet recruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age21-70
SponsorVanderbilt University Medical Center

About this trial

This prospective, single-center pilot study will evaluate metabolic flux dysregulation in adults with obesity and suspected or confirmed metabolic dysfunction-associated steatotic liver disease (MASLD) who are scheduled for protocol-eligible bariatric surgery at Vanderbilt University Medical Center. Participants will undergo research assessments before surgery, during the planned bariatric surgery encounter, and approximately 6 months after surgery. The study uses non-radioactive stable isotope tracer infusions, serial blood sampling, abdominal MRI/MRE, and research tissue specimens collected only during clinically planned bariatric surgery to quantify hepatic and extrahepatic metabolic fluxes. The primary objective is to determine how hepatic citric acid cycle flux and related metabolic pathways change after bariatric surgery and how these metabolic measures relate to liver fat, liver stiffness, and biopsy-graded MASLD/MASH severity.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Scheduled and clinically cleared for protocol-eligible bariatric surgery at Vanderbilt University Medical Center.

BMI ≥40 kg/m², or BMI >35 kg/m² with at least one obesity-associated comorbidity, such as type 2 diabetes, cardiovascular disease, hypertension, hyperlipidemia, obstructive sleep apnea, MASLD, osteoarthritis, or polycystic ovarian syndrome.

Able and willing to complete study procedures, including informed consent, questionnaires, blood draws, MRI/MRE imaging, stable isotope tracer infusion, and research tissue collection during planned bariatric surgery.

Able to provide informed consent in English.

Disqualifiers

Contraindication to MRI/MRE, including implanted cardiac defibrillator, pacemaker, or other MRI-incompatible implanted device.

Prior gastric or intestinal surgery, pancreatic surgery, or other prior surgery that, in the judgment of the study team or bariatric surgeon, would interfere with study procedures or outcome interpretation.

Active cancer or ongoing cancer treatment.

Presence or history of HIV infection.

Trial design

Design model

Single group

Treatments tested in this trial

  • Bariatric surgery

    Procedure/Surgery

    Clinically indicated bariatric surgery, such as Roux-en-Y gastric bypass or sleeve gastrectomy, performed as part of standard clinical care.

  • Stable isotope tracer infusion

    Other intervention

    Intravenous non-radioactive stable isotope tracers administered for research measurement of metabolic flux: \[¹³C₃\]lactate, \[6,6-²H₂\]-D-glucose, and \[9,9-²H₂\]palmitate.

  • MRI/MRE

    Diagnostic test

    Abdominal MRI proton density fat fraction and magnetic resonance elastography to assess hepatic fat and stiffness before surgery and approximately 6 months after surgery.

  • Research tissue collection during planned bariatric surgery

    Procedure/Surgery

    Liver, omentum, subcutaneous adipose tissue, and skeletal muscle specimens collected only during clinically planned bariatric surgery and only if safe in the surgeon's judgment.

Treatment groups

20 Participants
are divided into 1 treatment group
Group A: Bariatric Surgery Participants Undergoing Metabolic Flux AssessmentExperimental treatment 4 interventions

Trial outcomes

Primary outcomes

1

Change in hepatic citric acid cycle flux after bariatric surgery

Change in hepatic citric acid cycle flux estimated from stable isotope enrichment patterns, including \[¹³C₃\]lactate-based measurements, before bariatric surgery and approximately 6 months after surgery.

Time frame
Baseline/day of surgery to approximately 6 months post-surgery

Secondary outcomes

1

Change in hepatic gluconeogenic flux

Estimated from plasma glucose isotope enrichment and metabolic flux modeling

Time frame
Baseline/day of surgery to ~6 months
2

Change in endogenous glucose production

Estimated using \[6,6-²H₂\]-D-glucose tracer dilution

Time frame
Baseline/day of surgery to ~6 months
3

Change in free fatty acid turnover

Estimated using \[9,9-²H₂\]palmitate tracer dilution

Time frame
Baseline/day of surgery to ~6 months
4

Change in lactate turnover / lactate-related flux

Estimated using stable isotope enrichment patterns

Time frame
Baseline/day of surgery to ~6 months

Other outcomes

Locations

This trial has no locations.

Sponsors and contacts

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