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

7 agosto 2026 aggiornato da: 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.

Panoramica dello studio

Stato

Non ancora reclutamento

Condizioni

Intervento / Trattamento

Descrizione dettagliata

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.

Tipo di studio

Interventistico

Iscrizione (Stimato)

20

Fase

  • Non applicabile

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Contatto studio

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

  • Adulto
  • Adulto più anziano

Accetta volontari sani

No

Descrizione

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.

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Scienza basilare
  • Assegnazione: N / A
  • Modello interventistico: Assegnazione di gruppo singolo
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: 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.
Procedura: Bariatric surgery
Clinically indicated bariatric surgery, such as Roux-en-Y gastric bypass or sleeve gastrectomy, performed as part of standard clinical care.
Altri nomi:
  • Roux-en-Y-gastric byass
  • sleeve gastrectomey
Altro: 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.
Test diagnostico: 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.
Altri nomi:
  • risonanza magnetica
  • magnetic resonance elastography
Procedura: 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.

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Change in hepatic citric acid cycle flux after bariatric surgery
Lasso di tempo: 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

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Change in hepatic gluconeogenic flux
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: Baseline to ~6 months
Hepatic fat fraction quantified by MRI-PDFF
Baseline to ~6 months
Liver stiffness by MRE
Lasso di tempo: Baseline to ~6 months
Liver stiffness quantified by magnetic resonance elastography
Baseline to ~6 months
Histologic MASLD/MASH severity
Lasso di tempo: Intraoperative baseline only
Liver biopsy scored for steatosis, inflammation, ballooning, fibrosis, and MASLD activity score
Intraoperative baseline only
Extrahepatic metabolic fluxes
Lasso di tempo: Intraoperative baseline only
Metabolic fluxes in skeletal muscle, omentum, and subcutaneous adipose tissue estimated from intraoperative tissue specimens
Intraoperative baseline only
Serum inflammatory markers
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Vanderbilt University Medical Center

Investigatori

  • Investigatore principale: Charles R Flynn, PhD, Vanderbilt University Medical Center

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Stimato)

1 ottobre 2026

Completamento primario (Stimato)

30 settembre 2029

Completamento dello studio (Stimato)

1 gennaio 2060

Date di iscrizione allo studio

Primo inviato

7 agosto 2026

Primo inviato che soddisfa i criteri di controllo qualità

7 agosto 2026

Primo Inserito (Effettivo)

12 agosto 2026

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

12 agosto 2026

Ultimo aggiornamento inviato che soddisfa i criteri QC

7 agosto 2026

Ultimo verificato

1 agosto 2026

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • 260832

Piano per i dati dei singoli partecipanti (IPD)

Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?

SÌ

Descrizione del piano IPD

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.

Periodo di condivisione IPD

Data will be available within one year after study end.

Tipo di informazioni di supporto alla condivisione IPD

  • STUDIO_PROTOCOLLO
  • LINFA
  • ICF
  • RSI

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

No

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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