Metabolic Dysfunction-Associated Steatotic Liver DiseaseMASLDNCT07760909
Metabolic Flux Analysis in Metabolic Dysfunction-Associated Steatotic Liver Disease
A study testing Bariatric surgery, Stable isotope tracer infusion and MRI/MRE in people with Metabolic Dysfunction-Associated Steatotic Liver Disease and Metabolic Dysfunction-Associated Steatohepatitis, run by Vanderbilt University Medical Center.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 21 to 70 years
- Conditions the study is for
- Metabolic Dysfunction-Associated Steatotic Liver Disease, Metabolic Dysfunction-Associated Steatohepatitis, Obesity
- What is being tested?
- Bariatric surgery, Stable isotope tracer infusion and MRI/MRE
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- No sites listed yet
- Study dates
- 1 Oct 2026to 1 Jan 2060
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
- Alcohol use above study-defined limits: more than 14 alcoholic drinks per week for men or more than 7 alcoholic drinks per week for women, or illicit drug use that would interfere with safe participation or interpretation of study results.
- Anemia or other hematologic condition that would increase risk from study blood collection.
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- Abnormal ECG or clinically significant cardiovascular finding that would increase risk from study procedures.
- Impaired renal function or other clinically significant condition that would increase risk from study participation.
- Known Wilson's disease, alpha-1 antitrypsin deficiency, hemochromatosis, or other non-MASLD chronic liver disease that would confound interpretation of study outcomes.
- Any medical, surgical, or safety condition that, in the judgment of the PI, clinical co-investigator, CRC staff, anesthesia team, or bariatric surgeon, would make participation unsafe or interfere with completion of study procedures.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Metabolic Flux Analysis in MASLD
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.
Read the detailed description
MASLD and its progressive form MASH are associated with obesity, insulin resistance, altered hepatic substrate delivery, and changes in mitochondrial metabolism. However, the direction and significance of hepatic citric acid cycle flux changes in human MASLD remain unresolved. This study will apply in vivo metabolic flux analysis using non-radioactive stable isotope tracers to quantify hepatic and extrahepatic metabolic pathway activity in bariatric surgery participants before and after surgery.
Participants will complete three study timepoints. Approximately one week before surgery, participants will undergo fasting physical measurements, questionnaires, research blood collection, and abdominal MRI/MRE to quantify liver fat and stiffness. On the day of surgery, participants will receive intravenous infusions of [¹³C₃]lactate, [6,6-²H₂]-D-glucose, and [9,9-²H₂]palmitate for approximately 120 minutes with serial blood collection. During the clinically planned bariatric surgery, research tissue specimens may be collected from liver, omentum, subcutaneous adipose tissue, and skeletal muscle only if the surgeon determines collection can be performed safely without interfering with clinical care. Approximately 6 months after surgery, participants will repeat fasting physical measurements, questionnaires, MRI/MRE, stable isotope tracer infusion, and blood collection; no follow-up tissue biopsies will be collected.
Isotope enrichment patterns in plasma metabolites and tissue metabolites will be analyzed by mass spectrometry and modeled using metabolic flux analysis software to estimate hepatic citric acid cycle flux, gluconeogenesis, glucose turnover, free fatty acid turnover, lactate turnover, and selected extrahepatic metabolic fluxes. Liver fat and stiffness will be assessed by MRI/MRE, and intraoperative liver tissue will be scored for MASLD/MASH features using established histologic criteria.
- Conditions
- Metabolic Dysfunction-Associated Steatotic Liver Disease, Metabolic Dysfunction-Associated Steatohepatitis, Obesity, Bariatric Surgery
- Being tested
- Bariatric surgery, Stable isotope tracer infusion, MRI/MRE, Research tissue collection during planned bariatric surgery
- Keywords
- MASLD, MASH, metabolic flux analysis, stable isotope tracer, bariatric surgery, Roux-en-Y gastric bypass, sleeve gastrectomy, liver fat, magnetic resonance elastography, citric acid cycle, gluconeogenesis, free fatty acid turnover
- Medical subject headings
- Obesity, Fatty Liver
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bariatric surgeryProcedure or surgery
Also called Roux-en-Y-gastric byass, sleeve gastrectomey
Clinically indicated bariatric surgery, such as Roux-en-Y gastric bypass or sleeve gastrectomy, performed as part of standard clinical care.
Stable isotope tracer infusionOther
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/MREDiagnostic test
Also called magnetic resonance imaging, magnetic resonance elastography
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 surgeryProcedure or 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.
| Study group | Role | What they receive |
|---|---|---|
| Bariatric Surgery Participants Undergoing Metabolic Flux Assessment | Experimental | Adults scheduled and clinically cleared for protocol-eligible bariatric surgery at VUMC will undergo research MRI/MRE, blood collection, non-radioactive stable isotope tracer infusions, and intraoperative research tissue collection during planned bariatric surgery, followed by repeat noninvasive metabolic assessment approximately 6 months after surgery. Receives: Procedure: Bariatric surgery; Other: Stable isotope tracer infusion; Diagnostic Test: MRI/MRE; Procedure: Research tissue collection during planned bariatric surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline/day of surgery to approximately 6 months post-surgery
Secondary outcomes (11)
Change in hepatic gluconeogenic flux
Estimated from plasma glucose isotope enrichment and metabolic flux modeling
Measured: Baseline/day of surgery to ~6 months
Change in endogenous glucose production
Estimated using [6,6-²H₂]-D-glucose tracer dilution
Measured: Baseline/day of surgery to ~6 months
Change in free fatty acid turnover
Estimated using [9,9-²H₂]palmitate tracer dilution
Measured: Baseline/day of surgery to ~6 months
Change in lactate turnover / lactate-related flux
Estimated using stable isotope enrichment patterns
Measured: Baseline/day of surgery to ~6 months
Liver fat by MRI-PDFF
Hepatic fat fraction quantified by MRI-PDFF
Measured: Baseline to ~6 months
Liver stiffness by MRE
Liver stiffness quantified by magnetic resonance elastography
Measured: Baseline to ~6 months
Histologic MASLD/MASH severity
Liver biopsy scored for steatosis, inflammation, ballooning, fibrosis, and MASLD activity score
Measured: Intraoperative baseline only
Extrahepatic metabolic fluxes
Metabolic fluxes in skeletal muscle, omentum, and subcutaneous adipose tissue estimated from intraoperative tissue specimens
Measured: Intraoperative baseline only
Serum inflammatory markers
Research measurement of inflammatory markers including CRP, cytokines, adhesion molecules, and related biomarkers
Measured: Baseline/day of surgery; possibly ~6 months if collected
Metabolic hormone profile
Insulin, leptin, C-peptide, GLP-1, GIP, PYY, ghrelin
Measured: Baseline/day of surgery; possibly ~6 months if collected
Bile acid profile
Bile acids measured by LC-IM-MS
Measured: Baseline/day of surgery; possibly ~6 months if collected
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Aug 2026
- Study start1 Oct 2026 (estimated)
- Primary completion30 Sep 2029 (estimated)
- Study completion1 Jan 2060 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metabolic Dysfunction-Associated Steatotic Liver DiseaseStudies of the same condition, open and under way.
- More trials run by Vanderbilt University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Bariatric surgery
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Charles R. Flynn, Vanderbilt University Medical Center
- Investigators
- Charles R Flynn, PhD, Principal investigator, Vanderbilt University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07760909
- Sponsor's protocol ID
- 260832
- Acronym
- MASLD
- Status last verified
- Aug 2026
- First submitted
- 7 Aug 2026
- Last updated
- 12 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified or coded individual-level data and biospecimens may be shared for future research only as permitted by the informed consent document, IRB approval, institutional policy, data-use agreements, and applicable privacy protections. No direct identifiers will be included in publications, presentations, reports, or shared datasets.