- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT07760909
Metabolic Flux Analysis in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
Metabolic Flux Analysis in MASLD
Descripción general del estudio
Estado
Condiciones
Descripción detallada
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 estudio
Inscripción (Estimado)
Fase
- No aplica
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Charles R Flynn, PhD
- Número de teléfono: 615-343-8329
- Correo electrónico: MASLD.research@vumc.org
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
Descripción
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.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Ciencia básica
- Asignación: N / A
- Modelo Intervencionista: Asignación de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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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.
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Clinically indicated bariatric surgery, such as Roux-en-Y gastric bypass or sleeve gastrectomy, performed as part of standard clinical care.
Otros nombres:
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.
Otros nombres:
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.
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Change in hepatic citric acid cycle flux after bariatric surgery
Periodo de tiempo: Baseline/day of surgery to approximately 6 months post-surgery
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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.
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Baseline/day of surgery to approximately 6 months post-surgery
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Change in hepatic gluconeogenic flux
Periodo de tiempo: Baseline/day of surgery to ~6 months
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Estimated from plasma glucose isotope enrichment and metabolic flux modeling
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Baseline/day of surgery to ~6 months
|
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Change in endogenous glucose production
Periodo de tiempo: Baseline/day of surgery to ~6 months
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Estimated using [6,6-²H₂]-D-glucose tracer dilution
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Baseline/day of surgery to ~6 months
|
|
Change in free fatty acid turnover
Periodo de tiempo: Baseline/day of surgery to ~6 months
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Estimated using [9,9-²H₂]palmitate tracer dilution
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Baseline/day of surgery to ~6 months
|
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Change in lactate turnover / lactate-related flux
Periodo de tiempo: Baseline/day of surgery to ~6 months
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Estimated using stable isotope enrichment patterns
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Baseline/day of surgery to ~6 months
|
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Liver fat by MRI-PDFF
Periodo de tiempo: Baseline to ~6 months
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Hepatic fat fraction quantified by MRI-PDFF
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Baseline to ~6 months
|
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Liver stiffness by MRE
Periodo de tiempo: Baseline to ~6 months
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Liver stiffness quantified by magnetic resonance elastography
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Baseline to ~6 months
|
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Histologic MASLD/MASH severity
Periodo de tiempo: Intraoperative baseline only
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Liver biopsy scored for steatosis, inflammation, ballooning, fibrosis, and MASLD activity score
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Intraoperative baseline only
|
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Extrahepatic metabolic fluxes
Periodo de tiempo: Intraoperative baseline only
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Metabolic fluxes in skeletal muscle, omentum, and subcutaneous adipose tissue estimated from intraoperative tissue specimens
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Intraoperative baseline only
|
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Serum inflammatory markers
Periodo de tiempo: Baseline/day of surgery; possibly ~6 months if collected
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Research measurement of inflammatory markers including CRP, cytokines, adhesion molecules, and related biomarkers
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Baseline/day of surgery; possibly ~6 months if collected
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Metabolic hormone profile
Periodo de tiempo: Baseline/day of surgery; possibly ~6 months if collected
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Insulin, leptin, C-peptide, GLP-1, GIP, PYY, ghrelin
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Baseline/day of surgery; possibly ~6 months if collected
|
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Bile acid profile
Periodo de tiempo: Baseline/day of surgery; possibly ~6 months if collected
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Bile acids measured by LC-IM-MS
|
Baseline/day of surgery; possibly ~6 months if collected
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Charles R Flynn, PhD, Vanderbilt University Medical Center
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Estimado)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Trastornos Nutricionales
- Sobrenutrición
- Peso corporal
- Enfermedades del Sistema Digestivo
- Enfermedades del HIGADO
- Exceso de peso
- Condiciones Patológicas, Signos y Síntomas
- Enfermedades Nutricionales y Metabólicas
- Signos y síntomas
- Obesidad
- Hígado graso
- Terapéutica
- Técnicas y procedimientos de diagnóstico
- Diagnóstico
- Procedimientos quirúrgicos, operativo
- Tomografía
- Imágenes de diagnóstico
- Ultrasonografía
- Bariatría
- Gestión de la obesidad
- Imágenes de resonancia magnética
- Cirugía bariátrica
- Técnicas de imagen de elasticidad
Otros números de identificación del estudio
- 260832
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Descripción del plan IPD
Marco de tiempo para compartir IPD
Tipo de información de apoyo para compartir IPD
- PROTOCOLO DE ESTUDIO
- SAVIA
- CIF
- RSC
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
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