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

7 de agosto de 2026 atualizado por: 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.

Visão geral do estudo

Descrição detalhada

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 de estudo

Intervencional

Inscrição (Estimado)

20

Estágio

  • Não aplicável

Contactos e Locais

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Contato de estudo

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

  • Adulto
  • Adulto mais velho

Aceita Voluntários Saudáveis

Não

Descrição

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.

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

  • Finalidade Principal: Ciência básica
  • Alocação: N / D
  • Modelo Intervencional: Atribuição de grupo único
  • Mascaramento: Nenhum (rótulo aberto)

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Experimental: 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.
Clinically indicated bariatric surgery, such as Roux-en-Y gastric bypass or sleeve gastrectomy, performed as part of standard clinical care.
Outros nomes:
  • Roux-en-Y-gastric byass
  • sleeve gastrectomey
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.
Abdominal MRI proton density fat fraction and magnetic resonance elastography to assess hepatic fat and stiffness before surgery and approximately 6 months after surgery.
Outros nomes:
  • imagem de ressonância magnética
  • magnetic resonance elastography
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.

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Change in hepatic citric acid cycle flux after bariatric surgery
Prazo: 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

Medidas de resultados secundários

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

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Investigadores

  • Investigador principal: Charles R Flynn, PhD, Vanderbilt University Medical Center

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo (Estimado)

1 de outubro de 2026

Conclusão Primária (Estimado)

30 de setembro de 2029

Conclusão do estudo (Estimado)

1 de janeiro de 2060

Datas de inscrição no estudo

Enviado pela primeira vez

7 de agosto de 2026

Enviado pela primeira vez que atendeu aos critérios de CQ

7 de agosto de 2026

Primeira postagem (Real)

12 de agosto de 2026

Atualizações de registro de estudo

Última Atualização Postada (Real)

12 de agosto de 2026

Última atualização enviada que atendeu aos critérios de controle de qualidade

7 de agosto de 2026

Última verificação

1 de agosto de 2026

Mais Informações

Termos relacionados a este estudo

Plano para dados de participantes individuais (IPD)

Planeja compartilhar dados de participantes individuais (IPD)?

SIM

Descrição do plano 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.

Prazo de Compartilhamento de IPD

Data will be available within one year after study end.

Tipo de informação de suporte de compartilhamento de IPD

  • PROTOCOLO DE ESTUDO
  • SEIVA
  • CIF
  • CSR

Informações sobre medicamentos e dispositivos, documentos de estudo

Estuda um medicamento regulamentado pela FDA dos EUA

Não

Estuda um produto de dispositivo regulamentado pela FDA dos EUA

Não

Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .

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