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- Ensaio Clínico NCT07760909
Metabolic Flux Analysis in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
Metabolic Flux Analysis in MASLD
Visão geral do estudo
Status
Condições
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
Inscrição (Estimado)
Estágio
- Não aplicável
Contactos e Locais
Contato de estudo
- Nome: Charles R Flynn, PhD
- Número de telefone: 615-343-8329
- E-mail: MASLD.research@vumc.org
Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
- Adulto
- Adulto mais velho
Aceita Voluntários Saudáveis
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
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:
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:
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
|
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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
Patrocinador
Investigadores
- Investigador principal: Charles R Flynn, PhD, Vanderbilt University Medical Center
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Estimado)
Conclusão Primária (Estimado)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
- Distúrbios Nutricionais
- Supernutrição
- Peso corporal
- Doenças do aparelho digestivo
- Doenças do Fígado
- Excesso de peso
- Condições Patológicas, Sinais e Sintomas
- Doenças Nutricionais e Metabólicas
- Sinais e sintomas
- Obesidade
- Fígado gordo
- Terapêutica
- Técnicas e procedimentos de diagnóstico
- Diagnóstico
- Procedimentos cirúrgicos, operatórios
- Tomografia
- Diagnóstico imagens
- Ultrassonografia
- Bariatria
- Gerenciamento de obesidade
- Ressonância magnética
- Cirurgia bariátrica
- Técnicas de imagem de elasticidade
Outros números de identificação do estudo
- 260832
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
Descrição do plano IPD
Prazo de Compartilhamento de IPD
Tipo de informação de suporte de compartilhamento de IPD
- PROTOCOLO DE ESTUDO
- SEIVA
- CIF
- CSR
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