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

NCT04502212 | Completed Results FDA Device

• 1 other identifier: GE Research HUI-01
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This research study is being done to evaluate the effect of hepatic ultrasound insonification on whole-body insulin sensitivity and evaluate the safety and tolerability of hepatic ultrasound insonification in subjects with Type 2 Diabetes Mellitus (T2DM). "Insonify/insonification" is defined as applying to an area or an object carefully-controlled sound waves, typically as in ultrasound imaging. GE Research is sponsoring this research study. The purpose of this research study is to:

• Evaluate the effect of liver ultrasound waves on changes from baseline in whole-body insulin sensitivity
• Test the safety and tolerability of liver ultrasound waves in subjects with Type 2 Diabetes Mellitus
• Evaluate the effect of liver ultrasound waves on change from baseline in glucose tolerance and insulin secretion
• Evaluate the effect of liver ultrasound waves on glucose metabolism Insulin sensitivity refers to how sensitive the body's cells are in response to insulin. Glucose tolerance refers to the body's ability to handle (tolerate) glucose. Insulin secretion is a process in which the body releases insulin in response to glucose levels in the blood becoming elevated. The study device used in this study is cleared for use by the United States Food and Drug Administration (FDA) for ultrasound diagnostic exams, however it has not been tested or approved specifically for modulation of metabolism in people with diabetes. The use of the study device in this study is investigational and is considered a Non-Significant Risk (NSR).

Conditions

Type 2 Diabetes

Outcome Measures

Primary Outcomes (4)

• Change From Baseline in Glucose Disposal Rate: Insulin Ratio During Steady State (M/I)

  To evaluate the effect of hepatic ultrasound insonification on changes from baseline in whole-body insulin sensitivity during a two-step hyperinsulinemic, euglycemic clamp with stable isotope labeled glucose tracer

  Day 2 (Baseline) to Day 17

• Change From Baseline in Endogenous Glucose Production (EGP)

  To evaluate the effect of hepatic ultrasound insonification on changes from baseline in whole-body insulin sensitivity during a two-step hyperinsulinemic, euglycemic clamp with stable isotope labeled glucose tracer

  Day 2 (Baseline) to Day 17

• Change From Baseline in Insulin-Mediated EGP Suppression During the Clamp Timepoint With Low Rate Insulin Infusion (Step 1)

  To evaluate the effect of hepatic ultrasound insonification on changes from baseline in whole-body insulin sensitivity during a two-step hyperinsulinemic, euglycemic clamp with stable isotope labeled glucose tracer For each clamp, the degree of EGP suppression from the fasting EGP value was to be determined during the last 30 minutes point during each step of the two-step H-E clamp using the following equation: % EGP suppression = 1 - (EGP clamp/EGP fasting) Partial suppression of EGP during Step 1 was to be assessed to determine hepatic insulin sensitivity and EGP suppression during Step 2 was to be measured to confirm that EGP was (near) fully suppressed to allow the determination of extrahepatic insulin sensitivity.

  Day 2 (Baseline) to Day 17

• Change From Baseline in Rate of Glucose Disappearance (Rd)

  To evaluate the effect of hepatic ultrasound insonification on changes from baseline in whole-body insulin sensitivity during a two-step hyperinsulinemic, euglycemic clamp with stable isotope labeled glucose tracer

  Day 2 (Baseline) to Day 17

Secondary Outcomes (26)

• Incidence of Adverse Device Effects (ADEs) With a Severity Score of 1: Treatment Emergent Adverse Events (TEAEs) by System Organ Class and Preferred Term

  Screening to Day 28

• Incidence of Clinically Significant Laboratory Abnormalities

  Screening to Day 28

• Incidence of Significant Clinical Findings on Physical Examination

  Screening to Day 28

• Change From Baseline in Vital Signs: Blood Pressure

  Baseline to Day 28 - Baseline was defined as the last non-missing value collected prior to the first on study hepatic ultrasound insonification

• Change From Baseline in Vital Signs: Pulse Rate

  Baseline to Day 28 - Baseline was defined as the last non-missing value collected prior to the first on study hepatic ultrasound insonification

Other Outcomes (8)

• Change From Baseline in Exploratory Biomarkers

  Baseline to Day 18 - Baseline was defined as the last non-missing value collected prior to the first on study hepatic ultrasound insonification

• Change From Baseline in Long-term Glucose Parameters: Fructosamine

  Baseline to Day 18 - Baseline was defined as the last non-missing value collected prior to the first on study hepatic ultrasound insonification

• Change From Baseline in Long-term Glucose Parameters: Hemoglobin A1C

  Baseline to Day 18 - Baseline was defined as the last non-missing value collected prior to the first on study hepatic ultrasound insonification

Study Arms (1)

Insonification

EXPERIMENTAL

All subjects enrolled will receive a 3-day, 15 minute per day ultrasound insonification targeting the portis hepatis (liver).

Device: Hepatic Ultrasound Insonification

Interventions

Hepatic Ultrasound Insonification DEVICE

Hepatic ultrasound insonification will be performed after an overnight fast (no food or drinks except for water for at least 10 hours) at approximately the same time on each day for three days.

Insonification

Eligibility Criteria

• Age: 21 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects with type 2 diabetes ≥ 12 months.
• Age ≥ 21 and ≤ 75 years.
• Stable treatment with diet and exercise or stable treatment with metformin monotherapy. Stable treatment is defined as no change in treatment during the last 3 months.
• HbA1c \> 6.5% and\< 10% by local laboratory analysis (one retest is permitted with the result of the last test being conclusive).
• Body Mass Index (BMI) ≥ 18 to ≤ 35.0 kg/m2.
• Waist circumference ≤ 40 inches (≤ 102 cm).
• Considered generally healthy upon completion of medical history, physical examination and biochemical investigations as judged by the Principal Investigator.
• Female subjects must be non-pregnant and non-lactating and have a negative serum pregnancy test at Screening. Females may be surgically sterile, postmenopausal or of child-bearing potential. Females of childbearing potential must be using an acceptable method of birth control.
• Ability to provide written informed consent.

You may not qualify if:

• 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).
• 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).
• 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.
• 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.
• 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).
• Treatment with antihypertensive medication is not allowed, unless antihypertensive medication is given on a stable dose for at least 2 months prior to screening.
• 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).
• Subjects with a history or clinically active malignancy (history of basal cell carcinoma \[BCC\] is allowed).
• 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.
• Transient ischemic attack \[TIA\], cerebral infarct, or cerebral hemorrhage.
• Invasive cardiovascular procedure, such as coronary artery bypass graft surgery (CABG), or angioplasty/percutaneous coronary intervention (PCI) within 6 months of screening.
• 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.
• 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).
• 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).
• 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.

Sponsors & Collaborators

• General Electric Research: lead
• ProSciento, Inc.: collaborator

Study Sites (1)

ProSciento

Chula Vista, California, 91911, United States

Location

Related Publications (1)

• Levy JC, Matthews DR, Hermans MP. Correct homeostasis model assessment (HOMA) evaluation uses the computer program. Diabetes Care. 1998 Dec;21(12):2191-2. doi: 10.2337/diacare.21.12.2191. No abstract available.

  PMID: 9839117 BACKGROUND

Related Links

• Related Info

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Limitations and Caveats

The Safety Population consisted of subjects who received hepatic ultrasound insonification and included 16 subjects. The Ultrasound Insonification Effect Population consisted of subjects who received hepatic ultrasound insonification and included 15 subjects. Subject 101-029 had unevaluable data and was excluded from Ultrasound Insonification Effect Population. Subject 101-012 had clamp protocol deviation, and Ultrasound Insonification Effect Population was also analyzed excluding subject.

Results Point of Contact

• Title: Diane Minas
• Organization: GE Research

minas@ge.com

(518)698-3959

Study Officials

• Bridgette Boggess Franey, MD

  ProSciento, Inc.

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 29, 2020
• First Posted: August 6, 2020
• Study Start: July 30, 2020
• Primary Completion: May 24, 2021
• Study Completion: May 24, 2021
• Last Updated: June 2, 2022
• Results First Posted: June 2, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)