Pilot Study to Assess the Effects of Hepatic Ultrasound Insonification on Subjects With T2DM

Exclusion Criteria

• •1. History or current diagnosis with T1DM or T2DM subjects on insulin or other injectable therapies not allowed for this study (as listed in table of Prohibited Medication below).
• •2. A subject who is already indicated for medication escalation of their current diabetic therapy, or, who based upon study entry criteria, would be indicated for medication escalation during the course of the study (as assessed by the qualified Principal Investigator).
• •3. A subject who has diabetic complications, i.e., acute proliferative retinopathy or maculopathy, severe gastroparesis, and/or severe neuropathy, in particular autonomic neuropathy, as judged by the Principal Investigator.
• •4. Recurrent severe hypoglycemia (more than 1 event ≤ 6 month) or hypoglycemic unawareness or recent severe ketoacidosis (hospitalization ≤ 6 month), as judged by the Principal Investigator.
• •5. Persistent systolic blood pressure \> 150 mm Hg and/or diastolic blood pressure \> 95 mm Hg at screening. (Subjects may be re-checked once on the same day).
• •6. Treatment with antihypertensive medication is not allowed, unless antihypertensive medication is given on a stable dose for at least 2 months prior to screening.
• •7. Subjects with a clinically significant history or active disease of any of the following body systems: pulmonary, neurological (including dementia, neurodegenerative disease, movement disorder, spinal disorders), pancreatic (including pancreatitis), immunological or systemic inflammatory (including systemic lupus erythematosus \[SLE\], rheumatoid arthritis \[RA\]), dermatological, endocrine, genitourinary or hematological (including sickle cell anemia or other anemia syndromes, monocytosis, thrombocytopenia).
• •8. Subjects with a history or clinically active malignancy (history of basal cell carcinoma \[BCC\] is allowed).
• •9. History or current diagnosis of cardiac dysrhythmias or heart disease, defined as symptomatic heart failure (New York Heart Association class III or IV), myocardial infarction, unstable angina requiring medication.
• •10. Transient ischemic attack \[TIA\], cerebral infarct, or cerebral hemorrhage.
• •11. Invasive cardiovascular procedure, such as coronary artery bypass graft surgery (CABG), or angioplasty/percutaneous coronary intervention (PCI) within 6 months of screening.
• •12. PHistory of or presence of clinically significant ECG findings (e.g., QTcF \> 450 msec for males, QTcF \> 470 msec for females, LBBB) at Screening, or cardiac arrhythmia requiring medical or surgical treatment within 6 months prior to screening.
• •13. History of renal disease or abnormal kidney function tests at Screening (glomerular filtration rate \[GFR\] \< 60 mL/min/1.73m2 as estimated using the MDRD equation).
• •14. History or clinically significant active hepatic disease or clinically significant abnormal hepatic function tests at Screening suggestive of hepatic impairment (e.g., ALT and/or AST \>2 x ULN), total bilirubin \> 1 x ULN).
• •15. Subjects with a history or presence of any psychiatric disorder that, in the opinion of the Principal Investigator, might confound the results of the trial or pose additional risk in administering the investigational product to the subject.
• •16. Personal or family history of hypercoagulability or thromboembolic disease, including deep vein thrombosis and/or pulmonary embolism (PE)
• •17. History of surgical treatment for obesity (bariatric surgery, gastric banding, etc.) or any other gastrointestinal surgery (including appendectomy, cholecystectomy), any malabsorption disorder, severe gastroparesis, any GI procedure for weight loss (including LAP-BAND®), as well as clinically significant gastrointestinal disorders (e.g. peptic ulcers, severe GERD) at Screening.
• •18. History of any major surgery within 3 months prior to screening.
• •19. Any nerve stimulation study or implanted stimulator, including previously or currently implanted vagus nerve stimulator, previously or currently implanted spinal cord stimulator, other implanted electronic medical device, such as implanted pacemaker or cardioverter/defibrillator (AICD) or history of seizures.
• •20. Diagnosis of sleep apnea.
• •21. Participation in an investigational study within 30 days of screening or 5 half-lives within the last dose of any investigational product given during the investigational study, whichever is longer.
• •22. Current use of any drugs (other than current treatment for diabetes mellitus) that are known to interfere with glucose or insulin metabolism as stated below in table prohibited medication.
• •23. Thyroid hormone use is not allowed unless medication is given on a stable dose for at least 3 months prior to screening.
• •24. Chronic use of acetaminophen, and inability to wash-out and abstain from use during the study, as it would interfere with the CGMS assessment.
• •25. Subject is unable to tolerate adhesive tape or has any unresolved adverse skin reaction in the area of the sensor placement.
• •26. Implanted pacemaker or cardioverter/defibrillator (AICD).
• •27. Daily use of more than 5 cigarettes/day or equivalent use of any tobacco- or nicotine-containing product (such as, but not limited to vaping, transdermal nicotine patch, nicotine gum use, etc.) within 4 weeks prior to screening. Subjects must be able to abstain from any tobacco or nicotine containing products during confinement period.
• •28. Any use of marijuana within 4 weeks prior to screening and positive test at screening.
• •29. History of any active infection, except mild viral disease, such as common cold, within 30 days prior to screening.
• •30. History of any recent traumatic injury, including intracerebral hemorrhage and visceral injury.
• •31. History of alcohol or illicit drug abuse as judged by the Principal Investigator within past 12 months or positive test at screening. Any use of alcohol within 4 days prior to baseline assessment. Subjects must be able to abstain from any alcohol during confinement period.
• •32. Known history or positive test for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV Ab), human immunodeficiency virus type 1 (HIV-1) or type 2 (HIV-2)
• •33. Donation or loss of \> 500 mL of blood or blood product within 56 days prior to screening
• •34. Mental incapacity, unwillingness or language barriers precluding adequate understanding and to follow verbal commands during the ultrasound session or cooperation.
• •35. An abdominal ultrasound scan or exam within 1 month prior to screening and/or any pre-planned ultrasound examinations during the study, or the need to participate in any unplanned outside ultrasound procedures during study.