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Metabolic Flux Analysis in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

7. august 2026 opdateret af: Charles R. Flynn, Vanderbilt University Medical Center

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.

Studieoversigt

Status

Ikke rekrutterer endnu

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

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.

Undersøgelsestype

Interventionel

Tilmelding (Anslået)

20

Fase

  • Ikke anvendelig

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiekontakt

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

  • Voksen
  • Ældre voksen

Tager imod sunde frivillige

Ingen

Beskrivelse

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  • 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.

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Grundvidenskab
  • Tildeling: N/A
  • Interventionel model: Enkelt gruppeopgave
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: Bariatric Surgery Participants Undergoing Metabolic Flux Assessment
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.
Procedure: Bariatric surgery
Clinically indicated bariatric surgery, such as Roux-en-Y gastric bypass or sleeve gastrectomy, performed as part of standard clinical care.
Andre navne:
  • Roux-en-Y-gastric byass
  • sleeve gastrectomey
Andet: Stable isotope tracer infusion
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.
Diagnostisk test: MRI/MRE
Abdominal MRI proton density fat fraction and magnetic resonance elastography to assess hepatic fat and stiffness before surgery and approximately 6 months after surgery.
Andre navne:
  • MR scanning
  • magnetic resonance elastography
Procedure: Research tissue collection during planned bariatric 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.

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Change in hepatic citric acid cycle flux after bariatric surgery
Tidsramme: Baseline/day of surgery to approximately 6 months post-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.
Baseline/day of surgery to approximately 6 months post-surgery

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Change in hepatic gluconeogenic flux
Tidsramme: Baseline/day of surgery to ~6 months
Estimated from plasma glucose isotope enrichment and metabolic flux modeling
Baseline/day of surgery to ~6 months
Change in endogenous glucose production
Tidsramme: Baseline/day of surgery to ~6 months
Estimated using [6,6-²H₂]-D-glucose tracer dilution
Baseline/day of surgery to ~6 months
Change in free fatty acid turnover
Tidsramme: Baseline/day of surgery to ~6 months
Estimated using [9,9-²H₂]palmitate tracer dilution
Baseline/day of surgery to ~6 months
Change in lactate turnover / lactate-related flux
Tidsramme: Baseline/day of surgery to ~6 months
Estimated using stable isotope enrichment patterns
Baseline/day of surgery to ~6 months
Liver fat by MRI-PDFF
Tidsramme: Baseline to ~6 months
Hepatic fat fraction quantified by MRI-PDFF
Baseline to ~6 months
Liver stiffness by MRE
Tidsramme: Baseline to ~6 months
Liver stiffness quantified by magnetic resonance elastography
Baseline to ~6 months
Histologic MASLD/MASH severity
Tidsramme: Intraoperative baseline only
Liver biopsy scored for steatosis, inflammation, ballooning, fibrosis, and MASLD activity score
Intraoperative baseline only
Extrahepatic metabolic fluxes
Tidsramme: Intraoperative baseline only
Metabolic fluxes in skeletal muscle, omentum, and subcutaneous adipose tissue estimated from intraoperative tissue specimens
Intraoperative baseline only
Serum inflammatory markers
Tidsramme: Baseline/day of surgery; possibly ~6 months if collected
Research measurement of inflammatory markers including CRP, cytokines, adhesion molecules, and related biomarkers
Baseline/day of surgery; possibly ~6 months if collected
Metabolic hormone profile
Tidsramme: Baseline/day of surgery; possibly ~6 months if collected
Insulin, leptin, C-peptide, GLP-1, GIP, PYY, ghrelin
Baseline/day of surgery; possibly ~6 months if collected
Bile acid profile
Tidsramme: Baseline/day of surgery; possibly ~6 months if collected
Bile acids measured by LC-IM-MS
Baseline/day of surgery; possibly ~6 months if collected

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Vanderbilt University Medical Center

Efterforskere

  • Ledende efterforsker: Charles R Flynn, PhD, Vanderbilt University Medical Center

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Anslået)

1. oktober 2026

Primær færdiggørelse (Anslået)

30. september 2029

Studieafslutning (Anslået)

1. januar 2060

Datoer for studieregistrering

Først indsendt

7. august 2026

Først indsendt, der opfyldte QC-kriterier

7. august 2026

Først opslået (Faktiske)

12. august 2026

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

12. august 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

7. august 2026

Sidst verificeret

1. august 2026

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • 260832

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

JA

IPD-planbeskrivelse

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.

IPD-delingstidsramme

Data will be available within one year after study end.

IPD-deling Understøttende informationstype

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • CSR

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