Metabolic Flux Analysis in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
Metabolic Flux Analysis in MASLD
調査の概要
状態
詳細な説明
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.
研究の種類
入学 (推定)
段階
- 適用できない
連絡先と場所
研究連絡先
- 名前：Charles R Flynn, PhD
- 電話番号：615-343-8329
- メール：MASLD.research@vumc.org
参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
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.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：基礎科学
- 割り当て：なし
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：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.
他の名前：
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.
他の名前：
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.
|
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Change in hepatic citric acid cycle flux after bariatric surgery
時間枠：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
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Change in hepatic gluconeogenic flux
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：Baseline to ~6 months
|
Hepatic fat fraction quantified by MRI-PDFF
|
Baseline to ~6 months
|
|
Liver stiffness by MRE
時間枠：Baseline to ~6 months
|
Liver stiffness quantified by magnetic resonance elastography
|
Baseline to ~6 months
|
|
Histologic MASLD/MASH severity
時間枠：Intraoperative baseline only
|
Liver biopsy scored for steatosis, inflammation, ballooning, fibrosis, and MASLD activity score
|
Intraoperative baseline only
|
|
Extrahepatic metabolic fluxes
時間枠：Intraoperative baseline only
|
Metabolic fluxes in skeletal muscle, omentum, and subcutaneous adipose tissue estimated from intraoperative tissue specimens
|
Intraoperative baseline only
|
|
Serum inflammatory markers
時間枠：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
時間枠：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
時間枠：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
|
協力者と研究者
捜査官
- 主任研究者：Charles R Flynn, PhD、Vanderbilt University Medical Center
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
キーワード
追加の関連 MeSH 用語
その他の研究ID番号
- 260832
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD プランの説明
IPD 共有時間枠
IPD 共有サポート情報タイプ
- STUDY_PROTOCOL
- SAP
- ICF
- CSR
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。