Growth Hormone Releasing Hormone Analog to Improve Nonalcoholic Fatty Liver Disease and Associated Cardiovascular Risk

Inclusion Criteria:

1. Men and women 18-70yo

2. Body mass index (BMI) ≥ 30kg/m2

3. Hepatic steatosis as demonstrated by either a) Grade 1+ steatosis on a liver biopsy
performed within 12 months of the baseline visit, without >10% reduction in body
weight or addition of medications to treat fatty liver, or b) liver fat fraction ≥5%
on hydrogen-magnetic resonance spectroscopy (1H-MRS)

4. Hepatitis C antibody and Hepatitis B surface antigen negative

5. For females ≥50yo, negative mammogram within 1 year of baseline

6. If use of vitamin E ≥400 international units daily, stable dose for ≥6 mos

Exclusion Criteria:

1. Heavy alcohol use defined as consumption of > 20 grams daily for women or > 30 grans
daily for men for at least 3 consecutive months over the past 5 years assessed using
the Lifetime Drinking History Questionnaire

2. Known diagnosis of diabetes, use of any anti-diabetic medications (including
thiazolidinediones or metformin), fasting glucose >126mg/dL, or hemoglobin A1c (HbA1c)
≥7%

3. Use of any specific pharmacological treatments for NAFLD/nonalcoholic steatohepatitis
except vitamin E

4. Known cirrhosis, Child-Pugh score ≥7, stage 4 fibrosis on biopsy, or clinical evidence
of cirrhosis or portal hypertension on imaging or exam. If a subject is not known to
be cirrhotic at screen but is found to be cirrhotic based on the results of liver
biopsy at baseline, this subject will be referred to a hepatologist for clinical care
and will be excluded from further participation in the study.

5. Chronic systemic corticosteroid use in the ≤6 months prior to the baseline visit

6. Chronic use of Actigall, methotrexate, amiodarone, or tamoxifen

7. Known diagnosis of alpha-1 antitrypsin deficiency, Wilson's disease, hemochromatosis,
or autoimmune hepatitis

8. Use of growth hormone or growth hormone releasing hormone within the past 1 year

9. Change in lipid lowering or anti-hypertensive regimen within 2 months of screening

10. Hemoglobin < 10.0 g/dL or Creatinine >1.5mg/dL

11. Active malignancy

12. For men, history of prostate cancer or evidence of prostate malignancy by prostate
specific antigen (PSA) > 5 ng/mL

13. Severe chronic illness judged by the investigator to present a contraindication to
participation

14. History of hypopituitarism, head irradiation or any other condition known to affect
the GH axis

15. Use of physiologic testosterone (men) or estrogen or progesterone (women) unless
stable use for a year or more prior to study entry

16. Routine magnetic resonance imaging (MRI) exclusion criteria such as the presence of a
pacemaker or cerebral aneurysm clip

17. Weight loss surgery within 2 years before baseline. Weight loss surgery more than 2
years prior to baseline visit is permissible as long as no active weight loss (<10%
decrease in weight over past 6 months)

18. For women, positive urine pregnancy test (hCG), trying to achieve pregnancy, or
breastfeeding

19. Known hypersensitivity to tesamorelin or mannitol

20. Contraindication to receiving beta-blocker or nitroglycerin (which are part of the
coronary angiography)

21. Significant radiation exposure, including any history of radiation therapy, or any of
the following in the 12 months prior to randomization: a) more than 2 percutaneous
coronary interventions; b) more than 2 myocardial perfusion studies; 3) more than 2
computed tomography angiograms

22. Active consideration for a procedure or treatment that involves significant radiation
exposure as defined above in the 12 months following randomization

23. Not willing or able to adhere to dose schedules and required procedures per protocol

24. Judged by the investigator to be inappropriate for the study for other reasons not
detailed above.