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Completed

NCT Number: NCT00701376

Hepatic Effects of Gastric Bypass Surgery

Liver disease in the morbidly obese is thought to occur due to the long-term presence of fat deposits in the liver, resulting in inflammation and scarring of the liver over time, which reduces liver function. However, many of these patients are unaware that their liver is damaged. There is currently no consensus regarding what the long-term effects of gastric bypass surgery are on pre-existing liver disease in morbidly obese patients. This study will determine the long-term effects on the liver after this type of surgical procedure.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Cleveland Clinic

Cleveland, Ohio, 44159, United States

About this study

Before or on the day of surgery liver function will be determined using the DDG-2001 Analyzer. This monitor is able to detect the concentration of a dye called indocyanine green dye (ICG) when present in the blood stream. A dose of 0.5 mg/kg of ICG will be injected into an IV in the arm. Over approximately fifteen minutes the DDG-2001 Analyzer will determine how quickly the liver removes the dye ICG from the blood stream. This value represents how well the liver is functioning. Blood samples are drawn before injection of ICG to measure liver function using standard liver function tests.

This same routine for injecting ICG and obtaining blood for routine liver function tests will happen one more time, after surgery, once the subject has lost a significant amount of the original weight (60% of excess weight). This amount of weight loss typically occurs between 12 to 18 months after gastric bypass surgery. This second ICG measurement will occur during an outpatient follow-up visit to CCF.

A biopsy will be taken from the liver during surgery. A second biopsy taken after the 60% weight loss will be compared to determine the effect of this surgery on the liver.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • BMI > 40.
  • Documented failed non-surgical treatment for morbid obesity.
  • Ability to undergo long-term follow-up after LGBS.

Exclusion criteria

  • BMI < 40.
  • Subject age < 18 years.
  • Inability to undergo long-term follow-up after LGBS (living distance > 300 miles).
  • Patients with known ESLD.
  • Patients found to have evidence of ESLD during preoperative evaluation for LGBS including portal hypertension, ascites, and coagulopathy.
  • Patients with known iodine sensitivity or allergy.

Treatment and study plan

liver biopsy

Other

Subjects undergoing laparoscopic gastric surgery will be evaluated for liver function by comparing liver tissue biopsied during surgery with tissue biopsied after 60% weight loss

Other names: liver, needle, biopsy

Primary outcomes

  1. Aspartate Transaminase (AST) Change

    Time frame: from before surgery to the time when they lost 60% of their preoperative excess weight or weight loss had plateaued after this procedure

    To assess the liver function change from before surgery to the time when they lost 60% of their preoperative excess weight or weight loss had plateaued after this procedure (after the procedure minus versus before the procedure)

  2. Alanine Transaminase (ALT) Change

    Time frame: from before surgery to the time when they lost 60% of their preoperative excess weight or weight loss had plateaued after this procedure

    To assess the liver function change from before surgery to the time when they lost 60% of their preoperative excess weight or weight loss had plateaued after this procedure (after the procedure minus versus before the procedure)

  3. Alkaline Phosphate (ALK)

    Time frame: from before surgery to the time when they lost 60% of their preoperative excess weight or weight loss had plateaued after this procedure

    To assess the liver function change from before surgery to the time when they lost 60% of their preoperative excess weight or weight loss had plateaued after this procedure

  4. Total Bilirubin

    Time frame: from before surgery to the time when they lost 60% of their preoperative excess weight or weight loss had plateaued after this procedure

    To assess the liver function change from before surgery to the time when they lost 60% of their preoperative excess weight or weight loss had plateaued after this procedure (after the procedure minus versus before the procedure)

  5. Albumin

    Time frame: from before surgery to the time when they lost 60% of their preoperative excess weight or weight loss had plateaued after this procedure (after the procedure minus versus before the procedure)

    To assess the change in liver function from before surgery to the time when they lost 60% of their preoperative excess weight or weight loss had plateaued after this procedure (after the procedure versus before the procedure)

  6. Prothrombin Time (PT)

    Time frame: from before surgery to the time when they lost 60% of their preoperative excess weight or weight loss had plateaued after this procedure (after the procedure minus versus before the procedure)

    To assess the change in liver function from before surgery to the time when they lost 60% of their preoperative excess weight or weight loss had plateaued after this procedure (after the procedure minus versus before the procedure)

  7. Partial Thromboplastin Time (PTT)

    Time frame: from before surgery to the time when they lost 60% of their preoperative excess weight or weight loss had plateaued after this procedure (after the procedure minus versus before the procedure)

    To measure the change of PTT from before surgery to the time when they lost 60% of their preoperative excess weight or weight loss had plateaued after this procedure (after the procedure minus versus before the procedure)

  8. Indocyanine Green (ICG) K Value

    Time frame: from before surgery to the time when they lost 60% of their preoperative excess weight or weight loss had plateaued after this procedure (after the procedure minus versus before the procedure)

    To assess the liver function change from before surgery to the time when they lost 60% of their preoperative excess weight or weight loss had plateaued after this procedure (after the procedure minus versus before the procedure). ICG-k value is the slope of the decay curve of the serum ICG clearance graph, which is used to assess the liver function as it represents the rate of disappearance of ICG from blood as the liver exclusively distracts it. The lower k value means a lower rate of ICG clearance, indicating a worse liver function.

  9. Number of Subjects of Nonalcoholic Steatohepatitis (NAS Steatosis)

    Time frame: when patients lost 60% of their preoperative excess weight or weight loss had plateaued.

    To compare the distribution of NAS steatosis stage from before surgery to when patients lost 60% of their preoperative excess weight or weight loss had plateaued. The NAFLD activity score (NAS) from the NASH clinical Clinic Research Network is the unweighted sum of scores for steatosis, lobular inflammation, and ballooning hepatocyte degeneration, and ranges from zero to eight points. The histological reporting for grading steatosis was based on a scale of 0 to 3, with 0 being no steatosis (<5%), 1 being mild steatosis (involving 5-33% of the biopsy specimen), 2 being moderate steatosis (involving 34-66% of the specimen), and 3 being severe (involving >66%).

  10. Number of Subjects of Nonalcoholic Steatohepatitis Lobular Inflammation

    Time frame: when patients lost 60% of their preoperative excess weight or weight loss had plateaued.

    Lobular inflammation was similarly scored by number of foci per 200× magnification field (0 no foci: 1 < 2 foci: 2, 2-4 foci; 3, >4 foci) on biopsy specimen under microscope. This outcome was compared on its distribution before the surgery and once patients lost 60% of their preoperative excess weight or weight loss had plateaued.

  11. Fibrosis

    Time frame: after surgery once they lost 60% of their preoperative excess weight or weight loss had plateaued

    Fibrosis was measured from before surgery to after surgery once they lost 60% of their preoperative excess weight or weight loss had plateaued through biopsies

  12. Nonalcoholic Steatohepatitis (NAS) Hepatocyte Balloon

    Time frame: once patients lost 60% of their preoperative excess weight or weight loss had plateaued after surgery

    Ballooning hepatocyte degeneration was scored as 0 (absent), 1 (few, difficult to identify), 2 (many, easily identified). This was to assess the change in the distribution of NAS hepatocyte ballon between before the surgery and once patients lost 60% of their preoperative excess weight or weight loss had plateaued

Secondary outcomes

  1. Diagnostic Accuracy-AST

    Time frame: before RYGB surgery

    AST was measured before RYGB surgery and was used to fit a univariate logistic model to predict clinically asymptomatic but significant fatty liver, including NASH and NASH plus fibrosis. The AUC (area under the curve) of the receiver operating characteristic curve (ROC) was calculated with a 99.4% confidence interval. The x-axis of ROC is the false positive rate (%) and the y-axis is the true positive rate (%). The AUC value of ROC represents the performance of diagnostic measures/models, the higher value means better performance in general. The range of AUC is from 0 to 1.0 (perfect performance).

  2. Diagnostic Accuracy-ALT

    Time frame: before RYGB surgery

    ALT was measured before RYGB surgery and was used to fit a univariate logistic model to predict clinically asymptomatic but significant fatty liver, including NASH and NASH plus fibrosis. The AUC (area under the curve) of the receiver operating characteristic curve (ROC) was calculated with a 99.4% confidence interval. The x-axis of ROC is the false positive rate and the y-axis is the true positive rate. The AUC of ROC represents the performance of diagnostic measures/models, the higher score means better performance in general. The range of AUC is from 0 to 1.0.

  3. Diagnostic Accuracy-ALK

    Time frame: before RYGB surgery

    ALK was measured before RYGB surgery and was used to fit a univariate logistic model to predict clinically asymptomatic but significant fatty liver, including NASH and NASH plus fibrosis. The AUC (area under the curve) of the receiver operating characteristic curve (ROC) was calculated with a 99.4% confidence interval. The AUC (area under the curve) of the receiver operating characteristic curve (ROC) was calculated with a 99.4% confidence interval. The x-axis of ROC is the false positive rate and the y-axis is the true positive rate. The AUC of ROC represents the performance of diagnostic measures/models, the higher score means better performance in general. The range of AUC is from 0 to 1.0.

  4. Diagnostic Accuracy-total Bilirubin

    Time frame: before RYGB surgery

    The total bilirubin was measured before RYGB surgery and was used to fit a univariate logistic model to predict clinically asymptomatic but significant fatty liver, including NASH and NASH plus fibrosis. The AUC (area under the curve) of the receiver operating characteristic curve (ROC) was calculated with a 99.4% confidence interval. The AUC (area under the curve) of the receiver operating characteristic curve (ROC) was calculated with a 99.4% confidence interval. The x-axis of ROC is the false positive rate (%) and the y-axis is the true positive rate (%). The AUC of ROC represents the performance of diagnostic measures/models, the higher score means better performance in general. The range of AUC is from 0 to 1.0.

  5. Diagnostic Accuracy-PT

    Time frame: before RYGB surgery

    PT was measured before RYGB surgery and was used to fit a univariate logistic model to predict clinically asymptomatic but significant fatty liver, including NASH and NASH plus fibrosis. The AUC (area under the curve) of the receiver operating characteristic curve (ROC) was calculated with a 99.4% confidence interval. The AUC (area under the curve) of the receiver operating characteristic curve (ROC) was calculated with a 99.4% confidence interval. The x-axis of ROC is the false positive rate (%) and the y-axis is the true positive rate (%). The AUC value of ROC represents the performance of diagnostic measures/models, the higher value means better performance in general. The range of AUC is from 0 to 1.0 (perfect performance).

  6. Diagnostic Accuracy-PTT

    Time frame: before RYGB surgery

    PTT (Partial Thromboplastin Time) was measured before RYGB surgery and was used to fit a univariate logistic model to predict clinically asymptomatic but significant fatty liver, including NASH and NASH plus fibrosis. The AUC (area under the curve) of the receiver operating characteristic curve (ROC) was calculated with a 99.4% confidence interval. The AUC (area under the curve) of the receiver operating characteristic curve (ROC) was calculated with a 99.4% confidence interval. The x-axis of ROC is the false positive rate (%) and the y-axis is the true positive rate (%). The AUC value of ROC represents the performance of diagnostic measures/models, the higher value means better performance in general. The range of AUC is from 0 to 1.0 (perfect performance).

  7. Diagnostic Accuracy-ICG k Value

    Time frame: before RYGB surgery

    ICG k value was measured before RYGB surgery and was used to fit a univariate logistic model to predict clinically asymptomatic but significant fatty liver, including NASH and NASH plus fibrosis. The AUC (area under the curve) of the receiver operating characteristic curve (ROC) was calculated with a 99.4% confidence interval. The AUC (area under the curve) of the receiver operating characteristic curve (ROC) was calculated with a 99.4% confidence interval. The x-axis of ROC is the false positive rate (%) and the y-axis is the true positive rate (%). The AUC value of ROC represents the performance of diagnostic measures/models, the higher value means better performance in general. The range of AUC is from 0 to 1.0 (perfect performance).

  8. Diagnostic Accuracy-albumin

    Time frame: before RYGB surgery

    Albumin was measured before RYGB surgery and was used to fit a univariate logistic model to predict clinically asymptomatic but significant fatty liver, including NASH and NASH plus fibrosis. The AUC (area under the curve) of the receiver operating characteristic curve (ROC) was calculated with a 99.4% confidence interval. The AUC (area under the curve) of the receiver operating characteristic curve (ROC) was calculated with a 99.4% confidence interval. The x-axis of ROC is the false positive rate (%) and the y-axis is the true positive rate (%). The AUC value of ROC represents the performance of diagnostic measures/models, the higher value means better performance in general. The range of AUC is from 0 to 1.0 (perfect performance).

  9. Diagnostic Accuracy-multiple Factor

    Time frame: before RYGB surgery

    We also built a multivariable model using all preoperative liver function tests and ICG k clearance values to predict NASH (nonalcoholic steatohepatitis) from pre-RYGB values. AUC was used to assess the prediction performance of those multiple factors. The AUC (area under the curve) of the receiver operating characteristic curve (ROC) was calculated with a 95% confidence interval. The x-axis of ROC is the false positive rate (%) and the y-axis is the true positive rate (%). The AUC value of ROC represents the performance of diagnostic measures/models, the higher value means better performance in general. The range of AUC is from 0 to 1.0 (perfect performance).

Sponsors and collaborators

Lead sponsor

The Cleveland Clinic

Other

Registry information

Official study title

Long Term Hepatic Effects of Gastric Bypass Surgery

Important dates

Study start
2008
Primary completion
2014
Study completion
2014
First posted
Jun 19, 2008
Registry last updated
Jun 19, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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