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| ID | Type | Description | Link |
|---|---|---|---|
| U01DK061737 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | NIH |
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We hypothesize that exenatide (Byetta), a GLP-1 agonist administered subcutaneously for 24-28 weeks improves liver histology in diabetic patients with biopsy-proven NASH.
Eight adult patients with known type 2 DM(Diabetic) and biopsy-proven NAFLD were treated with 5-10 mcg subcutaneous exenatide for 28 weeks. Liver histology was assessed using the NAFLD Activity Score (NAS) prior to therapy and after 28 weeks of therapy. We used the following criteria to define our primary outcome: (i) no worsening of fibrosis score, (ii) improved score by at least one point in hepatocyte ballooning, (iii) either (a) improvement in NAS by 2 or more points spread across at least two of the three NAS components, or (b) post-treatment NAS equal or greater than 3.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| A pre treatment NAS score | Experimental | liver biopsy score pre treatment with exenatide 5 micrograms SQ (sub-cutaneous) twice a day titrated to 10 mcg SQ twice a day as tolerated |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Exenatide | Drug | 5 mcg twice a day titrated to 10 mcg twice a day |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients With Improvement in Liver Histology After Treatment With Exenatide | Number of patients with liver histology improved with exenatide. The improvement of liver histology was defined as (1) no worsening of the fibrosis score, (11) improved score by at least one point in hepatocyte ballooning, and (111) either (a) improvement in NAS (NAFLD Activity Score) by two points spread across as least two of the three NAS components, or by (B)post-treatment NAS<3. | between baseline and 24-28 weeks after initiating treatment |
| Change in NAS | The NAFLD Activity Score (NAS) is an underweight sum of steatosis (score 0-3), inflammation (score 0-3), ballooning scores (0-2). The NAS can range from 0-8 with the higher score indicating more aggressive disease. | Between baseline and 28 weeks of treatment with exenatide, sub q, 5-10 mcq. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Naga Chalasani, MD | Indiana University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Indiana University | Indianapolis | Indiana | 46202 | United States | ||
| Kansas City VA Medical Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 16012941 | Background | Adams LA, Lymp JF, St Sauver J, Sanderson SO, Lindor KD, Feldstein A, Angulo P. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology. 2005 Jul;129(1):113-21. doi: 10.1053/j.gastro.2005.04.014. | |
| 15017611 | Background | Younossi ZM, Gramlich T, Matteoni CA, Boparai N, McCullough AJ. Nonalcoholic fatty liver disease in patients with type 2 diabetes. Clin Gastroenterol Hepatol. 2004 Mar;2(3):262-5. doi: 10.1016/s1542-3565(04)00014-x. |
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This was a single arm, open label study. Only study group received exenatide treatment. Eight adult patients with known type 2 DM and biopsy-proven NAFLD were treated with 5-10mcg subcutaneous exenatide for 28 week.All eight patients were started on exenatide 5 mcg injections twice a day and the dose was increased to 10 mcg injections twice a day
2 recruitment sites: Department of Gastroenterology, San Antonio Uniformed Services Health Consortium, San Antonio, Texas, USA. Indiana University School of Medicine, Indianapolis, IN, USA
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| ID | Title | Description |
|---|---|---|
| FG000 | Exenatide Group | Exenatide 5 micrograms SQ twice a day titrated to 10 mcg SQ twice a day as tolerated Exenatide : 5 mcg twice a day titrated to 10 mcg twice a day |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
eight adult patients with known type 2 DM and biopsy -proven NAFLD were treated with 5-10 subcutaneous exenatide for 28 weeks
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| ID | Title | Description |
|---|---|---|
| BG000 | Open-labeled Prospective Case Series | Exenatide 5 micrograms SQ twice a day titrated to 10 mcg SQ twice a day as tolerated Exenatide: 5 mcg twice a day titrated to 10 mcg twice a day |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of 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 | Number of Patients With Improvement in Liver Histology After Treatment With Exenatide | Number of patients with liver histology improved with exenatide. The improvement of liver histology was defined as (1) no worsening of the fibrosis score, (11) improved score by at least one point in hepatocyte ballooning, and (111) either (a) improvement in NAS (NAFLD Activity Score) by two points spread across as least two of the three NAS components, or by (B)post-treatment NAS<3. | Posted | Number | participants | between baseline and 24-28 weeks after initiating treatment |
|
|
28 weeks
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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 | Exenatide Group | Exenatide 5 micrograms SQ twice a day titrated to 10 mcg SQ twice a day as tolerated Exenatide : 5 mcg twice a day titrated to 10 mcg twice a day |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| abdominal pain along with nausea | Gastrointestinal disorders | CTCAE | Systematic Assessment |
As a case series our findings are limited by a control group and a small number of subjects enrolled. These limitations are tempered by the single expert hepatologist and the stringent definitions for histological improvement, ((primary end point)..
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Patrick R Kenney, DO | Department of Gastroenterology, San Antonio Uniformed Services Health Consortium | pat.kenney@us.army.mil |
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| 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 |
|---|---|
| D000077270 | Exenatide |
| ID | Term |
|---|---|
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D014688 | Venoms |
| D045424 | Complex Mixtures |
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| Kansas City |
| Missouri |
| United States |
| Fort Sam Houston | San Antonio | Texas | United States |
| 12843147 | Background | Kolterman OG, Buse JB, Fineman MS, Gaines E, Heintz S, Bicsak TA, Taylor K, Kim D, Aisporna M, Wang Y, Baron AD. Synthetic exendin-4 (exenatide) significantly reduces postprandial and fasting plasma glucose in subjects with type 2 diabetes. J Clin Endocrinol Metab. 2003 Jul;88(7):3082-9. doi: 10.1210/jc.2002-021545. |
| 14752837 | Background | Promrat K, Lutchman G, Uwaifo GI, Freedman RJ, Soza A, Heller T, Doo E, Ghany M, Premkumar A, Park Y, Liang TJ, Yanovski JA, Kleiner DE, Hoofnagle JH. A pilot study of pioglitazone treatment for nonalcoholic steatohepatitis. Hepatology. 2004 Jan;39(1):188-96. doi: 10.1002/hep.20012. |
| 15017657 | Background | Shadid S, Jensen MD. Effect of pioglitazone on biochemical indices of non-alcoholic fatty liver disease in upper body obesity. Clin Gastroenterol Hepatol. 2003 Sep;1(5):384-7. doi: 10.1053/s1542-3565(03)00198-8. |
| 14512888 | Background | Neuschwander-Tetri BA, Brunt EM, Wehmeier KR, Oliver D, Bacon BR. Improved nonalcoholic steatohepatitis after 48 weeks of treatment with the PPAR-gamma ligand rosiglitazone. Hepatology. 2003 Oct;38(4):1008-17. doi: 10.1053/jhep.2003.50420. |
| 1700785 | Background | Eng J, Andrews PC, Kleinman WA, Singh L, Raufman JP. Purification and structure of exendin-3, a new pancreatic secretagogue isolated from Heloderma horridum venom. J Biol Chem. 1990 Nov 25;265(33):20259-62. |
| 1313797 | Background | Eng J, Kleinman WA, Singh L, Singh G, Raufman JP. Isolation and characterization of exendin-4, an exendin-3 analogue, from Heloderma suspectum venom. Further evidence for an exendin receptor on dispersed acini from guinea pig pancreas. J Biol Chem. 1992 Apr 15;267(11):7402-5. |
| 9020121 | Background | Chen YE, Drucker DJ. Tissue-specific expression of unique mRNAs that encode proglucagon-derived peptides or exendin 4 in the lizard. J Biol Chem. 1997 Feb 14;272(7):4108-15. doi: 10.1074/jbc.272.7.4108. |
| 10027577 | Background | Greig NH, Holloway HW, De Ore KA, Jani D, Wang Y, Zhou J, Garant MJ, Egan JM. Once daily injection of exendin-4 to diabetic mice achieves long-term beneficial effects on blood glucose concentrations. Diabetologia. 1999 Jan;42(1):45-50. doi: 10.1007/s001250051111. |
| 21131943 | Result | Kenny PR, Brady DE, Torres DM, Ragozzino L, Chalasani N, Harrison SA. Exenatide in the treatment of diabetic patients with non-alcoholic steatohepatitis: a case series. Am J Gastroenterol. 2010 Dec;105(12):2707-9. doi: 10.1038/ajg.2010.363. No abstract available. |
| Participants |
|
| Age, Continuous | Mean | Inter-Quartile Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Number of participants who had NAFLD Activity Score (NAS) pre/post 24-28 wks. after treatment | The NAFLD Activity Score (NAS) is an underweight sum of steatosis (score 0-3), inflammation (score 0-3), ballooning scores (0-2). The NAS can range from 0-8 with the higher score indicating more aggressive disease. | Number | participants |
|
| NAS score | steatosis, inflammation, ballooning. Each catagory has a 1 to 3 value given and the total of all 3 catagories equals the NAS overall score. 1] The NAFLD Activity Score (NAS) is an underweight sum of steatosis (score 0-3), inflammation (score 0-3), ballooning scores (0-2). The NAS can range from 0-8 with the higher score indicating more aggressive disease | Median | Full Range | units on a scale |
|
| Counts |
|---|
| Participants |
|
|
| Primary | Change in NAS | The NAFLD Activity Score (NAS) is an underweight sum of steatosis (score 0-3), inflammation (score 0-3), ballooning scores (0-2). The NAS can range from 0-8 with the higher score indicating more aggressive disease. | Posted | Mean | Standard Deviation | units on a scale | Between baseline and 28 weeks of treatment with exenatide, sub q, 5-10 mcq. |
|
|
|
| 0 |
| 8 |
| 2 |
| 8 |
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| D014118 |
| Toxins, Biological |
| D001685 | Biological Factors |