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The purpose of this study is to evaluate imaging and other biomarkers of non-alcoholic fatty liver disease before and after bariatric surgery.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| NASH group | Experimental | These are individuals that have been identified as having NASH by MRE. Confirmation with liver biopsy required for continuation in the longitudinal study. |
|
| Non-NASH (NAFLD or normal) group | Active Comparator | These are individuals that do not have NASH. They either have normal liver physiology or only have evidence of hepatic steatosis. This group will be studied up until the day of their bariatric surgery and will serve as a comparator population with respect to baseline measurements. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Bariatric surgery | Procedure | Subjects enrolling in the study who are undergoing bariatric surgery as part of their medical care will be studied |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percent Change in Liver Fat Between Baseline and 12 Weeks Post-surgery | Assessed by magnetic resonance imaging proton density fat fraction (MRI PDFF) | 12 weeks |
| Percent Change in Liver Stiffness Between Baseline and12 Weeks Post-surgery | We will evaluate change in liver stiffness, a surrogate for fibrosis, as assessed by magnetic resonance elastography (MRE) | 12 weeks |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Steven Smith, MD | Study Principal Investigator | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Translational Research Institute for Metabolism and Diabetes | Orlando | Florida | 32804 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20299294 | Background | Ahmed MH, Abu EO, Byrne CD. Non-Alcoholic Fatty Liver Disease (NAFLD): new challenge for general practitioners and important burden for health authorities? Prim Care Diabetes. 2010 Oct;4(3):129-37. doi: 10.1016/j.pcd.2010.02.004. Epub 2010 Mar 17. | |
| 24042449 | Background | Loomba R, Sanyal AJ. The global NAFLD epidemic. Nat Rev Gastroenterol Hepatol. 2013 Nov;10(11):686-90. doi: 10.1038/nrgastro.2013.171. Epub 2013 Sep 17. |
| Label | URL |
|---|---|
| Translational Research Institute for Metabolism and Diabetes | View source |
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Recruitment began 7/18/2018 and concluded 12/3/2019. Participants were recruited from a local bariatric surgery medical practice.
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| ID | Title | Description |
|---|---|---|
| FG000 | NASH Group | These are individuals that have been identified as having NASH by MRE. Confirmation with liver biopsy required for continuation in the longitudinal study. Bariatric surgery: Subjects enrolling in the study who are undergoing bariatric surgery as part of their medical care will be studied HepQuant SHUNT Dual Cholate Liver Diagnostic Kit: For the experimental group, the device will be used to monitor the effect of bariatric surgery on liver function. For the active comparator group, the device will be used for the assessment of baseline liver function. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Oct 24, 2019 |
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| HepQuant SHUNT Dual Cholate Liver Diagnostic Kit | Device | For the experimental group, the device will be used to monitor the effect of bariatric surgery on liver function. For the active comparator group, the device will be used for the assessment of baseline liver function. |
|
| 21623852 | Background | Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther. 2011 Aug;34(3):274-85. doi: 10.1111/j.1365-2036.2011.04724.x. Epub 2011 May 30. |
| 25557690 | Background | Sanyal AJ, Friedman SL, McCullough AJ, Dimick-Santos L; American Association for the Study of Liver Diseases; United States Food and Drug Administration. Challenges and opportunities in drug and biomarker development for nonalcoholic steatohepatitis: findings and recommendations from an American Association for the Study of Liver Diseases-U.S. Food and Drug Administration Joint Workshop. Hepatology. 2015 Apr;61(4):1392-405. doi: 10.1002/hep.27678. Epub 2015 Mar 19. |
| 21700865 | Background | Cohen JC, Horton JD, Hobbs HH. Human fatty liver disease: old questions and new insights. Science. 2011 Jun 24;332(6037):1519-23. doi: 10.1126/science.1204265. |
| 15940625 | Background | Ratziu V, Charlotte F, Heurtier A, Gombert S, Giral P, Bruckert E, Grimaldi A, Capron F, Poynard T; LIDO Study Group. Sampling variability of liver biopsy in nonalcoholic fatty liver disease. Gastroenterology. 2005 Jun;128(7):1898-906. doi: 10.1053/j.gastro.2005.03.084. |
| 24683373 | Background | Alkhouri N, McCullough AJ. Noninvasive Diagnosis of NASH and Liver Fibrosis Within the Spectrum of NAFLD. Gastroenterol Hepatol (N Y). 2012 Oct;8(10):661-8. |
| 25866601 | Background | Papagianni M, Sofogianni A, Tziomalos K. Non-invasive methods for the diagnosis of nonalcoholic fatty liver disease. World J Hepatol. 2015 Apr 8;7(4):638-48. doi: 10.4254/wjh.v7.i4.638. |
| 27312947 | Background | Dulai PS, Sirlin CB, Loomba R. MRI and MRE for non-invasive quantitative assessment of hepatic steatosis and fibrosis in NAFLD and NASH: Clinical trials to clinical practice. J Hepatol. 2016 Nov;65(5):1006-1016. doi: 10.1016/j.jhep.2016.06.005. Epub 2016 Jun 14. |
| 27999641 | Background | Hashemi SA, Alavian SM, Gholami-Fesharaki M. Assessment of transient elastography (FibroScan) for diagnosis of fibrosis in non-alcoholic fatty liver disease: A systematic review and meta-analysis. Caspian J Intern Med. 2016 Fall;7(4):242-252. |
| 16454845 | Background | Barker KB, Palekar NA, Bowers SP, Goldberg JE, Pulcini JP, Harrison SA. Non-alcoholic steatohepatitis: effect of Roux-en-Y gastric bypass surgery. Am J Gastroenterol. 2006 Feb;101(2):368-73. doi: 10.1111/j.1572-0241.2006.00419.x. |
| 22418890 | Background | Rabl C, Campos GM. The impact of bariatric surgery on nonalcoholic steatohepatitis. Semin Liver Dis. 2012 Feb;32(1):80-91. doi: 10.1055/s-0032-1306428. Epub 2012 Mar 13. |
| 23431426 | Background | Hafeez S, Ahmed MH. Bariatric surgery as potential treatment for nonalcoholic fatty liver disease: a future treatment by choice or by chance? J Obes. 2013;2013:839275. doi: 10.1155/2013/839275. Epub 2013 Jan 29. |
| 27594839 | Background | Schneck AS, Anty R, Patouraux S, Bonnafous S, Rousseau D, Lebeaupin C, Bailly-Maitre B, Sans A, Tran A, Gugenheim J, Iannelli A, Gual P. Roux-En Y Gastric Bypass Results in Long-Term Remission of Hepatocyte Apoptosis and Hepatic Histological Features of Non-alcoholic Steatohepatitis. Front Physiol. 2016 Aug 19;7:344. doi: 10.3389/fphys.2016.00344. eCollection 2016. |
| 25869925 | Background | Alizai PH, Wendl J, Roeth AA, Klink CD, Luedde T, Steinhoff I, Neumann UP, Schmeding M, Ulmer F. Functional Liver Recovery After Bariatric Surgery--a Prospective Cohort Study with the LiMAx Test. Obes Surg. 2015 Nov;25(11):2047-53. doi: 10.1007/s11695-015-1664-0. |
| 22364559 | Background | Barr J, Caballeria J, Martinez-Arranz I, Dominguez-Diez A, Alonso C, Muntane J, Perez-Cormenzana M, Garcia-Monzon C, Mayo R, Martin-Duce A, Romero-Gomez M, Lo Iacono O, Tordjman J, Andrade RJ, Perez-Carreras M, Le Marchand-Brustel Y, Tran A, Fernandez-Escalante C, Arevalo E, Garcia-Unzueta M, Clement K, Crespo J, Gual P, Gomez-Fleitas M, Martinez-Chantar ML, Castro A, Lu SC, Vazquez-Chantada M, Mato JM. Obesity-dependent metabolic signatures associated with nonalcoholic fatty liver disease progression. J Proteome Res. 2012 Apr 6;11(4):2521-32. doi: 10.1021/pr201223p. Epub 2012 Mar 15. |
| 23634241 | Background | Nielsen MJ, Nedergaard AF, Sun S, Veidal SS, Larsen L, Zheng Q, Suetta C, Henriksen K, Christiansen C, Karsdal MA, Leeming DJ. The neo-epitope specific PRO-C3 ELISA measures true formation of type III collagen associated with liver and muscle parameters. Am J Transl Res. 2013 Apr 19;5(3):303-15. Print 2013. |
| 25308921 | Background | Nielsen MJ, Veidal SS, Karsdal MA, Orsnes-Leeming DJ, Vainer B, Gardner SD, Hamatake R, Goodman ZD, Schuppan D, Patel K. Plasma Pro-C3 (N-terminal type III collagen propeptide) predicts fibrosis progression in patients with chronic hepatitis C. Liver Int. 2015 Feb;35(2):429-37. doi: 10.1111/liv.12700. Epub 2014 Oct 29. |
| 25714706 | Background | Helmke S, Colmenero J, Everson GT. Noninvasive assessment of liver function. Curr Opin Gastroenterol. 2015 May;31(3):199-208. doi: 10.1097/MOG.0000000000000167. |
| 24440671 | Background | Schnabl B, Brenner DA. Interactions between the intestinal microbiome and liver diseases. Gastroenterology. 2014 May;146(6):1513-24. doi: 10.1053/j.gastro.2014.01.020. Epub 2014 Jan 15. |
| 24452634 | Background | Bonder A, Afdhal N. Utilization of FibroScan in clinical practice. Curr Gastroenterol Rep. 2014 Feb;16(2):372. doi: 10.1007/s11894-014-0372-6. |
| 21460032 | Background | Chen J, Talwalkar JA, Yin M, Glaser KJ, Sanderson SO, Ehman RL. Early detection of nonalcoholic steatohepatitis in patients with nonalcoholic fatty liver disease by using MR elastography. Radiology. 2011 Jun;259(3):749-56. doi: 10.1148/radiol.11101942. Epub 2011 Apr 1. |
| 24871333 | Background | Thomas MS, Newman D, Leinhard OD, Kasmai B, Greenwood R, Malcolm PN, Karlsson A, Rosander J, Borga M, Toms AP. Test-retest reliability of automated whole body and compartmental muscle volume measurements on a wide bore 3T MR system. Eur Radiol. 2014 Sep;24(9):2279-91. doi: 10.1007/s00330-014-3226-6. Epub 2014 May 29. |
| 25111561 | Background | Karlsson A, Rosander J, Romu T, Tallberg J, Gronqvist A, Borga M, Dahlqvist Leinhard O. Automatic and quantitative assessment of regional muscle volume by multi-atlas segmentation using whole-body water-fat MRI. J Magn Reson Imaging. 2015 Jun;41(6):1558-69. doi: 10.1002/jmri.24726. Epub 2014 Aug 11. |
| 27662190 | Background | West J, Dahlqvist Leinhard O, Romu T, Collins R, Garratt S, Bell JD, Borga M, Thomas L. Feasibility of MR-Based Body Composition Analysis in Large Scale Population Studies. PLoS One. 2016 Sep 23;11(9):e0163332. doi: 10.1371/journal.pone.0163332. eCollection 2016. |
| 24036007 | Background | Banerjee R, Pavlides M, Tunnicliffe EM, Piechnik SK, Sarania N, Philips R, Collier JD, Booth JC, Schneider JE, Wang LM, Delaney DW, Fleming KA, Robson MD, Barnes E, Neubauer S. Multiparametric magnetic resonance for the non-invasive diagnosis of liver disease. J Hepatol. 2014 Jan;60(1):69-77. doi: 10.1016/j.jhep.2013.09.002. Epub 2013 Sep 12. |
| 26471505 | Background | Pavlides M, Banerjee R, Sellwood J, Kelly CJ, Robson MD, Booth JC, Collier J, Neubauer S, Barnes E. Multiparametric magnetic resonance imaging predicts clinical outcomes in patients with chronic liver disease. J Hepatol. 2016 Feb;64(2):308-315. doi: 10.1016/j.jhep.2015.10.009. Epub 2015 Nov 10. |
| FG001 | Non-NASH (NAFLD or Normal) Group | These are individuals that do not have NASH. They either have normal liver physiology or only have evidence of hepatic steatosis. This group will be studied up until the day of their bariatric surgery and will serve as a comparator population with respect to baseline measurements. Bariatric surgery: Subjects enrolling in the study who are undergoing bariatric surgery as part of their medical care will be studied HepQuant SHUNT Dual Cholate Liver Diagnostic Kit: For the experimental group, the device will be used to monitor the effect of bariatric surgery on liver function. For the active comparator group, the device will be used for the assessment of baseline liver function. |
| COMPLETED |
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| NOT COMPLETED |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | NASH Group | These are individuals that have been identified as having NASH by MRE. Confirmation with liver biopsy required for continuation in the longitudinal study. Bariatric surgery: Subjects enrolling in the study who are undergoing bariatric surgery as part of their medical care will be studied HepQuant SHUNT Dual Cholate Liver Diagnostic Kit: For the experimental group, the device will be used to monitor the effect of bariatric surgery on liver function. For the active comparator group, the device will be used for the assessment of baseline liver function. |
| BG001 | Non-NASH (NAFLD or Normal) Group | These are individuals that do not have NASH. They either have normal liver physiology or only have evidence of hepatic steatosis. This group will be studied up until the day of their bariatric surgery and will serve as a comparator population with respect to baseline measurements. Bariatric surgery: Subjects enrolling in the study who are undergoing bariatric surgery as part of their medical care will be studied HepQuant SHUNT Dual Cholate Liver Diagnostic Kit: For the experimental group, the device will be used to monitor the effect of bariatric surgery on liver function. For the active comparator group, the device will be used for the assessment of baseline liver function. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percent Change in Liver Fat Between Baseline and 12 Weeks Post-surgery | Assessed by magnetic resonance imaging proton density fat fraction (MRI PDFF) | Only the NASH group had longitudinal evaluation | Posted | Mean | Standard Deviation | percent change | 12 weeks |
|
|
| ||||||||||||||||||||||||||||
| Primary | Percent Change in Liver Stiffness Between Baseline and12 Weeks Post-surgery | We will evaluate change in liver stiffness, a surrogate for fibrosis, as assessed by magnetic resonance elastography (MRE) | Only NASH group had longitudinal evaluation | Posted | Mean | Standard Deviation | percent change | 12 weeks |
|
2.22 years
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | NASH Group | These are individuals that have been identified as having NASH by MRE. Confirmation with liver biopsy required for continuation in the longitudinal study. Bariatric surgery: Subjects enrolling in the study who are undergoing bariatric surgery as part of their medical care will be studied HepQuant SHUNT Dual Cholate Liver Diagnostic Kit: For the experimental group, the device will be used to monitor the effect of bariatric surgery on liver function. For the active comparator group, the device will be used for the assessment of baseline liver function. | 0 | 4 | 0 | 4 | 2 | 4 |
| EG001 | Non-NASH (NAFLD or Normal) Group | These are individuals that do not have NASH. They either have normal liver physiology or only have evidence of hepatic steatosis. This group will be studied up until the day of their bariatric surgery and will serve as a comparator population with respect to baseline measurements. Bariatric surgery: Subjects enrolling in the study who are undergoing bariatric surgery as part of their medical care will be studied HepQuant SHUNT Dual Cholate Liver Diagnostic Kit: For the experimental group, the device will be used to monitor the effect of bariatric surgery on liver function. For the active comparator group, the device will be used for the assessment of baseline liver function. | 0 | 10 | 0 | 10 | 9 | 10 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Bruising, tenderness | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Cyst in pituitaty | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
| ||
| Ear Infection | Ear and labyrinth disorders | Systematic Assessment |
| ||
| Gas Pain | Gastrointestinal disorders | Systematic Assessment |
| ||
| H. Pylori Infection | Gastrointestinal disorders | Systematic Assessment |
| ||
| Headache | General disorders | Systematic Assessment |
| ||
| Inactive mild gastritis | Gastrointestinal disorders | Systematic Assessment |
| ||
| Lower Leg Pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Migraine | General disorders | Systematic Assessment |
| ||
| Pleural Effusion | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Right Arm Tenderness | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Shingles | Infections and infestations | Systematic Assessment |
| ||
| Sinus Infection | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Syncope | Nervous system disorders | Systematic Assessment |
| ||
| Tachycardia | Cardiac disorders | Systematic Assessment |
| ||
| Urinary Tract Infections | Infections and infestations | Systematic Assessment |
| ||
| Vitamin D Defficiency | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Worsening Hypertension | Cardiac disorders | Systematic Assessment |
| ||
| Abdominal Pain | Gastrointestinal disorders | Systematic Assessment |
|
This trial was limited by the need to close the trial prior to enrolling all participants due to extreme difficulties with recruitment. Based on our power estimates, we needed 25 people in the NASH group, and we were only able to enroll 4. Therefore, our analyses will be limited the basic plans proposed in the protocol and will likely be exploratory and hypothesis generating in nature.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Karen Corbin | AdventHealth Translational Research Institute | (407) 303-7100 | Karen.Corbin@AdventHealth.com |
| May 11, 2021 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D065626 | Non-alcoholic Fatty Liver Disease |
| ID | Term |
|---|---|
| D005234 | Fatty Liver |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| D050110 | Bariatric Surgery |
| ID | Term |
|---|---|
| D049088 | Bariatrics |
| D000073319 | Obesity Management |
| D013812 | Therapeutics |
| D013514 | Surgical Procedures, Operative |
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| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
|
|