Nonalcoholic Fatty Liver Disease
Conditions
Keywords
Non-alcoholic steatohepatitis, NASH
Brief summary
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.
Detailed description
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.
Interventions
DRUGExenatide
5 mcg twice a day titrated to 10 mcg twice a day
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Indiana University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Well documented NASH based on clinical and histological criteria. Liver biopsy must have been obtained within 12-months prior to initiation of the study. * Subjects must have known diabetes (either diet controlled or only on Metformin or sulfonylureas such as glyburide or glipizide). * Subjects must be 18 year or older.
Exclusion criteria
* Co-existing etiologies for chronic liver disease (hepatitis B or C, autoimmune or hemochromatosis, etc.). * Clinical or histological evidence of cirrhosis. * Alanine aminotransferase or aspartate aminotransferase \> 300 IU/L. * Uncontrolled diabetes (hemoglobin A1C greater than or equal to 9%). * Insulin or TZD dependant DM. * Known human immunodeficiency virus infection. * Current or history of significant alcohol consumption within past 5 years. Significant alcohol consumption is defined as \>20 grm/day in females and \>30 grms/day in males or if alcohol consumption cannot satisfactorily be quantified. * Serum creatinine of greater than or equal to 2 mg/dl. * Active, serious medical disease (cardiac, renal, pulmonary, dermatologic, psychiatric illness) with likely life expectancy less 5 years. * Current or previous malignancy with expected life expectancy less than 5-years (other than basal cell cancer of the skin). * Use of drugs historically associated with NASH. * Histological evidence of malignancy, 4+ iron deposition, or any other type of liver disease. * Active substance abuse, such as alcohol,inhaled or injection drugs with the previous one year. * Known intolerance or allergy to exenatide (Byetta). * History of neuroglycopenia. * Women of childbearing potential must have had a negative pregnancy test prior to starting the study and should be willing to avoid pregnancy during the study period. * Women must not be nursing.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Improvement in Liver Histology After Treatment With Exenatide | between baseline and 24-28 weeks after initiating treatment | 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. |
| Change in NAS | Between baseline and 28 weeks of treatment with exenatide, sub q, 5-10 mcq. | 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. |
Countries
United States
Participant flow
Recruitment details
2 recruitment sites: Department of Gastroenterology, San Antonio Uniformed Services Health Consortium, San Antonio, Texas, USA. Indiana University School of Medicine, Indianapolis, IN, USA
Pre-assignment details
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
Participants by arm
| Arm | Count |
|---|---|
| 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 | 8 |
| Total | 8 |
Baseline characteristics
| Characteristic | Open-labeled Prospective Case Series |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants |
| Age, Continuous | 54 years |
| NAS score | 4 units on a scale |
| Number of participants who had NAFLD Activity Score (NAS) pre/post 24-28 wks. after treatment | 8 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 2 / 8 |
| serious Total, serious adverse events | 0 / 8 |
Outcome results
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.
Time frame: Between baseline and 28 weeks of treatment with exenatide, sub q, 5-10 mcq.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment With Exenatide | Change in NAS | -1.5 units on a scale | Standard Deviation 1.66 |
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.
Time frame: between baseline and 24-28 weeks after initiating treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment With Exenatide | Number of Patients With Improvement in Liver Histology After Treatment With Exenatide | 8 participants |