Metabolic Flux Analysis in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
Metabolic Flux Analysis in MASLD
연구 개요
상태
상세 설명
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.
연구 유형
등록 (추정된)
단계
- 해당 없음
연락처 및 위치
연구 연락처
- 이름: Charles R Flynn, PhD
- 전화번호: 615-343-8329
- 이메일: MASLD.research@vumc.org
참여기준
자격 기준
공부할 수 있는 나이
- 성인
- 고령자
건강한 자원 봉사자를 받아들입니다
설명
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.
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 기초 과학
- 할당: 해당 없음
- 중재 모델: 단일 그룹 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
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실험적: 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.
다른 이름들:
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.
다른 이름들:
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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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Change in hepatic citric acid cycle flux after bariatric surgery
기간: 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
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Change in hepatic gluconeogenic flux
기간: 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
기간: 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
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Change in free fatty acid turnover
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: Baseline/day of surgery; possibly ~6 months if collected
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Bile acids measured by LC-IM-MS
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Baseline/day of surgery; possibly ~6 months if collected
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공동 작업자 및 조사자
수사관
- 수석 연구원: Charles R Flynn, PhD, Vanderbilt University Medical Center
연구 기록 날짜
연구 주요 날짜
연구 시작 (추정된)
기본 완료 (추정된)
연구 완료 (추정된)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
키워드
추가 관련 MeSH 약관
기타 연구 ID 번호
- 260832
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
IPD 계획 설명
IPD 공유 기간
IPD 공유 지원 정보 유형
- 연구_프로토콜
- 수액
- ICF
- CSR
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