Type 2 DiabetesNCT04502212
Pilot Study to Assess the Effects of Hepatic Ultrasound Insonification on Subjects With T2DM
A study testing Hepatic Ultrasound Insonification in people with Type 2 Diabetes, run by General Electric Research at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 21 to 75 years
- Conditions the study is for
- Type 2 Diabetes
- What is being tested?
- Hepatic Ultrasound Insonification
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Jul 2020to 24 May 2021
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
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- 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.
Who cannot join
- 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.
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- 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.
- Personal or family history of hypercoagulability or thromboembolic disease, including deep vein thrombosis and/or pulmonary embolism (PE)
- 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.
- History of any major surgery within 3 months prior to screening.
- 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.
- Diagnosis of sleep apnea.
- 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.
- 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.
- Thyroid hormone use is not allowed unless medication is given on a stable dose for at least 3 months prior to screening.
- Chronic use of acetaminophen, and inability to wash-out and abstain from use during the study, as it would interfere with the CGMS assessment.
- Subject is unable to tolerate adhesive tape or has any unresolved adverse skin reaction in the area of the sensor placement.
- Implanted pacemaker or cardioverter/defibrillator (AICD).
- 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.
- Any use of marijuana within 4 weeks prior to screening and positive test at screening.
- History of any active infection, except mild viral disease, such as common cold, within 30 days prior to screening.
- History of any recent traumatic injury, including intracerebral hemorrhage and visceral injury.
- 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.
- 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)
- Donation or loss of > 500 mL of blood or blood product within 56 days prior to screening
- Mental incapacity, unwillingness or language barriers precluding adequate understanding and to follow verbal commands during the ultrasound session or cooperation.
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open-Label, Pilot Study to Assess the Effects of Hepatic Ultrasound Insonification on Glucometabolic Parameters in Subjects With T2DM
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
Read more
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).
Read the detailed description
This was an open label, exploratory pilot study to assess the effects of hepatic ultrasound insonification on glucometabolic parameters in subjects with T2DM through selective hepatic ultrasound of the porta hepatis region of the liver utilizing pulsed ultrasound. The study was to consist of 1 cohort comprising up to 15 subjects. Dropouts and withdrawals could have been replaced until the anticipated number of subjects completed the study. Finally, the study consisted of one cohort with 36 subjects enrolled, including 20 screen failures, 15 subjects that completed the study (1 completer had an incorrect infusion parameter and was removed from clamp analysis), and 1 subject that was discontinued at the discretion of the Investigator. As this was an exploratory, open-label study, no randomization or blinding was performed and no-unblinding codes were required.
The study included a Screening Period, Observational Period 1, 3 consecutive days of hepatic ultrasound insonification, and Observational Period 2. Each Observational Period was divided into an In-house Period and an Outpatient Visit (OPV). The Screening Period was performed up to 28 days prior to the first In-house Period. For eligible subjects with a body mass index (BMI) > 35.0 and ≤ 40.0 kg/m2 and/or a waist circumference > 40 and ≤ 45 inches, an ultrasound examination was added to confirm eligibility, and the Screening Period was extended to at least 30 days. The first Observational Period lasted approximately 2-weeks (Days -1 to 14). On the morning of Day -1, subjects checked into the clinic for a 3-day In-house Period; subjects may have been released from the clinic on Day 2. Subjects were contacted via telephone every other day until the next In-house Period. On Day 8, subjects checked into the clinic for an OPV. On Day 15, subjects checked into the clinic in fasting conditions for a 4-day In-house Period. Insonifications were performed on three consecutive days (Days 15, 16 and 17). Subjects may have been released from the clinic on Day 18. The second Observational Period lasted 11 days (Days 18 to 28). Subjects were contacted via telephone every other day until the Follow-up Visit. On Day 22, subjects checked into the clinic for the OPV. The Follow-up Visit was performed on Day 28.
- Conditions
- Type 2 Diabetes
- Being tested
- Hepatic Ultrasound Insonification
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hepatic Ultrasound InsonificationDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| Insonification | Experimental | All subjects enrolled will receive a 3-day, 15 minute per day ultrasound insonification targeting the portis hepatis (liver). Receives: Device: Hepatic Ultrasound Insonification |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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.
Measured: 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
Measured: 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
To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM. Incidence of adverse device effects included observations of Incidence and severity of clinically significant laboratory abnormalities, Change from baseline in vital signs (blood pressure, temperature, respiratory rate, and heart rate), Incidence and severity of clinical findings on physical examination, Change from baseline in 12-lead electrocardiogram (ECG) parameters; the primary ECG endpoint was QTcF.
To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM: [Severity Score: 1=Mild; 2=Moderate; 3=Severe; 4=Life-Threatening; 5=Death]
Measured: Screening to Day 28
Incidence of Clinically Significant Laboratory Abnormalities
To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM
Measured: Screening to Day 28
Incidence of Significant Clinical Findings on Physical Examination
To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM
Measured: Screening to Day 28
Change From Baseline in Vital Signs: Blood Pressure
To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM
Measured: 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
To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM
Measured: 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: Respiratory Rate
To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM
Measured: 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: Temperature
To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM
Measured: Baseline to Day 28 - Baseline was defined as the last non-missing value collected prior to the first on study hepatic ultrasound insonification
Incidence of Clinically Significant Changes in Vital Sign Values
To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM
Measured: Screening to Day 28
Change From Baseline in 12-lead Electrocardiogram (ECG) Parameters
To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM
Measured: Baseline to Day 28 - Baseline was defined as the last non-missing value collected prior to the first on study hepatic ultrasound insonification
Incidence of Clinically Significant Changes in ECG Measurements
To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM
Measured: Screening to Day 28
Change From Baseline in Insulin Sensitivity Index (SI)
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.
The Insulin Sensitivity Index was to be calculated from the H-E clamp data using the formula included in the SAP, with Step 1 indicating the first phase of the clamp, or the period of administration of the first (lower) insulin infusion rate and Step 2 indicating the second phase of the clamp or the period of administration of the second (higher) insulin infusion rate. Mean GIRs and mean plasma insulin concentrations were to be calculated during steady state for the applicable step(s).
Change from baseline of SI was then to be computed for each subject as:
Change from baseline (SI) = SI2 - SI1, where Clamp 2 was the second clamp and Clamp 1 was the first clamp (completed on Day 2, prior to first insonification).
Measured: Day 2 (Baseline) to Day 17
Change From Baseline in Glucose Disposal Rate During Steady State (M)
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
Measured: Day 2 (Baseline) to Day 17
Change From Baseline in Glucose Metabolic Clearance Rate During Steady State (MCR)
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
Measured: Day 2 (Baseline) to Day 17
Change From Baseline in Homeostasis Model Assessment of Insulin Resistance (HOMA2-IR)
To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, assessed by a Homeostasis Model. A higher value denotes an increased level of insulin resistance, and a lower value denotes an decreased level of insulin resistance. The value is computed based on fasting insulin and glucose values.
The HOMA2 results were produced by the HOMA2 calculator with FPG and insulin concentration obtained from safety laboratory assessments as the inputs to the calculator at https://www.dtu.ox.ac.uk/homacalculator/. Please see citation (see references module): "Levy 1998 Levy JC, Matthews DR, \& Hermans MP. (1998). Correct homeostasis model assessment (HOMA) evaluation uses the computer program. Diabetes Care. 21:2191-2192."
Measured: Day 15 (Baseline) to Day 18
Change From Baseline in Homeostasis Model Assessment of Insulin Secretion (HOMA2-B)
To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, assessed by a Homeostasis Model. The HOMA2 results were to be produced by the HOMA2 calculator with FPG and insulin concentration obtained from safety laboratory assessments as the inputs to the calculator at https://www.dtu.ox.ac.uk/homacalculator/. HOMA2-B values estimate steady state pancreatic beta cell function, as a percent of a normal reference population. See citation: "Levy JC, Matthews DR, \& Hermans MP. (1998). Correct homeostasis model assessment (HOMA) evaluation uses the computer program. Diabetes Care. 21:2191-2192."
Measured: Day 15 (Baseline) to Day 18
Change From Baseline in Fasting Plasma Glucose (FPG)
To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, assessed by fasting plasma glucose blood test
Measured: 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 Oral Glucose Tolerance Test (OGTT) Area Under the Curve (AUC 0-180): Glucose
To evaluate the effect of hepatic ultrasound insonification on change from baseline in glucose tolerance and insulin secretion, assessed by an oral glucose tolerance test (OGTT). AUC in this outcome is calculated using the absolute value of glucose measures (compared to incremental AUC below which uses baseline (time 0 glucose) subtracted values).
Measured: Day 1 (Baseline) to Day 16
Change From Baseline in Oral Glucose Tolerance Test (OGTT) Area Under the Curve (AUC 0-180): Insulin
To evaluate the effect of hepatic ultrasound insonification on change from baseline in glucose tolerance and insulin secretion, assessed by an oral glucose tolerance test (OGTT). AUC in this outcome is calculated using the absolute value of insulin measures (compared to incremental AUC below which uses baseline (time 0 insulin) subtracted values).
Measured: Day 1 (Baseline) to Day 16
Change From Baseline in Continuous Glucose Monitoring System (CGMS): Time in Ranges
To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, assessed by a continuous glucose monitoring system (CGMS)
Measured: 14:00 on Day -1 to 22:00 on Day 1 (Baseline) to 14:00 on Day 15 to 22:00 on Day 16 - omitting data collected between a subject's OGTT glucose consumption start time + 180 minutes
Change From Baseline in Continuous Glucose Monitoring System (CGMS): Average Daily Glucose
To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, assessed by a continuous glucose monitoring system (CGMS)
Measured: 14:00 on Day -1 to 22:00 on Day 1 (Baseline) to 14:00 on Day 15 to 22:00 on Day 16 - omitting data collected between a subject's OGTT glucose consumption start time + 180 minutes
Change From Baseline in Continuous Glucose Monitoring System (CGMS): Blood Glucose Coefficient of Variation
To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, assessed by a continuous glucose monitoring system (CGMS)
Measured: 14:00 on Day -1 to 22:00 on Day 1 (Baseline) to 14:00 on Day 15 to 22:00 on Day 16 - omitting data collected between a subject's OGTT glucose consumption start time + 180 minutes
Change From Baseline in Continuous Glucose Monitoring System (CGMS): Low/High Blood Glucose Index
To evaluate the effect of hepatic ultrasound insonification on glucose metabolism parameters, assessed by a continuous glucose monitoring system (CGMS)
To calculate the LBGI and HBGI, the original BG data for each day/period was to be transformed such that it was centered by zero and bound between -sqrt(10) and sqrt(10).
f(BG,α,β) = [(ln(BG))1.084 - 5.381]*1.509
The transformed values were then to be input into the BG risk function:
r(BG) = 10 * f(BG,α,β)2
The risk of each observation was further to be transformed into two series, risk of low BG series, rl(BG), and risk of high BG series, rh(BG):
rl(BG) = r(BG) if f(BG) < 0 and 0 otherwise rh(BG) = r(BG) if f(BG) > 0 and 0 otherwise These series were then to be averaged to produce the LBGI and the HBGI as shown in the equations in the SAP.
Measured: 14:00 on Day -1 to 22:00 on Day 1 (Baseline) to 14:00 on Day 15 to 22:00 on Day 16 - omitting data collected between a subject's OGTT glucose consumption start time + 180 minutes
Incidence of Adverse Device Effects (ADEs) With a Severity Score of 2: Treatment Emergent Adverse Events (TEAEs) by System Organ Class and Preferred Term
To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM. Incidence of adverse device effects included observations of Incidence and severity of clinically significant laboratory abnormalities, Change from baseline in vital signs (blood pressure, temperature, respiratory rate, and heart rate), Incidence and severity of clinical findings on physical examination, Change from baseline in 12-lead electrocardiogram (ECG) parameters; the primary ECG endpoint was QTcF.
To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM: [Severity Score: 1=Mild; 2=Moderate; 3=Severe; 4=Life-Threatening; 5=Death]
Measured: Screening to Day 28
Incidence of Adverse Device Effects (ADEs) With a Severity Score of 3: Treatment Emergent Adverse Events (TEAEs) by System Organ Class and Preferred Term
To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM. Incidence of adverse device effects included observations of Incidence and severity of clinically significant laboratory abnormalities, Change from baseline in vital signs (blood pressure, temperature, respiratory rate, and heart rate), Incidence and severity of clinical findings on physical examination, Change from baseline in 12-lead electrocardiogram (ECG) parameters; the primary ECG endpoint was QTcF.
To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM: [Severity Score: 1=Mild; 2=Moderate; 3=Severe; 4=Life-Threatening; 5=Death]
Measured: Screening to Day 28
Incidence of Adverse Device Effects (ADEs) With a Severity Score of 4: Treatment Emergent Adverse Events (TEAEs) by System Organ Class and Preferred Term
To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM. Incidence of adverse device effects included observations of Incidence and severity of clinically significant laboratory abnormalities, Change from baseline in vital signs (blood pressure, temperature, respiratory rate, and heart rate), Incidence and severity of clinical findings on physical examination, Change from baseline in 12-lead electrocardiogram (ECG) parameters; the primary ECG endpoint was QTcF.
To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM: [Severity Score: 1=Mild; 2=Moderate; 3=Severe; 4=Life-Threatening; 5=Death]
Measured: Screening to Day 28
Incidence of Adverse Device Effects (ADEs) With a Severity Score of 5: Treatment Emergent Adverse Events (TEAEs) by System Organ Class and Preferred Term
To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM. Incidence of adverse device effects included observations of Incidence and severity of clinically significant laboratory abnormalities, Change from baseline in vital signs (blood pressure, temperature, respiratory rate, and heart rate), Incidence and severity of clinical findings on physical examination, Change from baseline in 12-lead electrocardiogram (ECG) parameters; the primary ECG endpoint was QTcF.
To evaluate safety and tolerability of hepatic ultrasound insonification in subjects with T2DM: [Severity Score: 1=Mild; 2=Moderate; 3=Severe; 4=Life-Threatening; 5=Death]
Measured: Screening to Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Aug 2020
- Study start30 Jul 2020
- Primary completion24 May 2021
- Study completion24 May 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Type 2 DiabetesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- General Electric Research
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- ProSciento, Inc.
- Responsible party
- Sponsor
- Investigators
- Bridgette Boggess Franey, MD, Principal investigator, ProSciento, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04502212
- Sponsor's protocol ID
- GE Research HUI-01
- Status last verified
- Mar 2022
- First submitted
- 29 Jul 2020
- Last updated
- 2 Jun 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 9839117
Study at a glance
From the registry record, last updated by the sponsor on 2 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Pilot Study to Assess the Effects of Hepatic Ultrasound Insonification on Glucometabolic Parameters in Subjects With T2DM
- ClinicalTrials.gov ID
- NCT04502212
- Acronym / sponsor ID
- GE Research HUI-01
- Conditions
- Type 2 Diabetes
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- General Electric ResearchIndustry (pharma, biotech, devices)
- Collaborators
- ProSciento, Inc.
- Study start
- 30 Jul 2020 (actual)
- Primary completion
- 24 May 2021 (actual)
- Study completion
- 24 May 2021 (actual)
- First posted
- 6 Aug 2020 (actual)
- Results
- Posted 2 Jun 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
This was an open label, exploratory pilot study to assess the effects of hepatic ultrasound insonification on glucometabolic parameters in subjects with T2DM through selective hepatic ultrasound of the porta hepatis region of the liver utilizing pulsed ultrasound. The study was to consist of 1 cohort comprising up to 15 subjects. Dropouts and withdrawals could have been replaced until the anticipated number of subjects completed the study. Finally, the study consisted of one cohort with 36 subjects enrolled, including 20 screen failures, 15 subjects that completed the study (1 completer had an incorrect infusion parameter and was removed from clamp analysis), and 1 subject that was discontinued at the discretion of the Investigator. As this was an exploratory, open-label study, no randomization or blinding was performed and no-unblinding codes were required.
The study included a Screening Period, Observational Period 1, 3 consecutive days of hepatic ultrasound insonification, and Observational Period 2. Each Observational Period was divided into an In-house Period and an Outpatient Visit (OPV). The Screening Period was performed up to 28 days prior to the first In-house Period. For eligible subjects with a body mass index (BMI) > 35.0 and ≤ 40.0 kg/m2 and/or a waist circumference > 40 and ≤ 45 inches, an ultrasound examination was added to confirm eligibility, and the Screening Period was extended to at least 30 days. The first Observational Period lasted approximately 2-weeks (Days -1 to 14). On the morning of Day -1, subjects checked into the clinic for a 3-day In-house Period; subjects may have been released from the clinic on Day 2. Subjects were contacted via telephone every other day until the next In-house Period. On Day 8, subjects checked into the clinic for an OPV. On Day 15, subjects checked into the clinic in fasting conditions for a 4-day In-house Period. Insonifications were performed on three consecutive days (Days 15, 16 and 17). Subjects may have been released from the clinic on Day 18. The second Observational Period lasted 11 days (Days 18 to 28). Subjects were contacted via telephone every other day until the Follow-up Visit. On Day 22, subjects checked into the clinic for the OPV. The Follow-up Visit was performed on Day 28.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Insonification | Experimental | Device: Hepatic Ultrasound InsonificationAll subjects enrolled will receive a 3-day, 15 minute per day ultrasound insonification targeting the portis hepatis (liver). |
Who may qualify
- Ages
- 21 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (35 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hepatic Ultrasound InsonificationHepatic 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. | Device | Insonification |
Primary outcome
Change From Baseline in Glucose Disposal Rate: Insulin Ratio During Steady State (M/I)
Time frame: Day 2 (Baseline) to Day 17
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
Change From Baseline in Endogenous Glucose Production (EGP)
Time frame: Day 2 (Baseline) to Day 17
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
Change From Baseline in Insulin-Mediated EGP Suppression During the Clamp Timepoint With Low Rate Insulin Infusion (Step 1)
Time frame: Day 2 (Baseline) to Day 17
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.
Change From Baseline in Rate of Glucose Disappearance (Rd)
Time frame: Day 2 (Baseline) to Day 17
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
26 secondary outcomes
Incidence of Adverse Device Effects (ADEs) With a Severity Score of 1: Treatment Emergent Adverse Events (TEAEs) by System Organ Class and Preferred Term
Time frame: Screening to Day 28
Incidence of Clinically Significant Laboratory Abnormalities
Time frame: Screening to Day 28
Incidence of Significant Clinical Findings on Physical Examination
Time frame: Screening to Day 28
Change From Baseline in Vital Signs: Blood Pressure
Time frame: 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
Time frame: 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: Respiratory Rate
Time frame: 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: Temperature
Time frame: Baseline to Day 28 - Baseline was defined as the last non-missing value collected prior to the first on study hepatic ultrasound insonification
Incidence of Clinically Significant Changes in Vital Sign Values
Time frame: Screening to Day 28
Change From Baseline in 12-lead Electrocardiogram (ECG) Parameters
Time frame: Baseline to Day 28 - Baseline was defined as the last non-missing value collected prior to the first on study hepatic ultrasound insonification
Incidence of Clinically Significant Changes in ECG Measurements
Time frame: Screening to Day 28
Change From Baseline in Insulin Sensitivity Index (SI)
Time frame: Day 2 (Baseline) to Day 17
Change From Baseline in Glucose Disposal Rate During Steady State (M)
Time frame: Day 2 (Baseline) to Day 17
Change From Baseline in Glucose Metabolic Clearance Rate During Steady State (MCR)
Time frame: Day 2 (Baseline) to Day 17
Change From Baseline in Homeostasis Model Assessment of Insulin Resistance (HOMA2-IR)
Time frame: Day 15 (Baseline) to Day 18
Change From Baseline in Homeostasis Model Assessment of Insulin Secretion (HOMA2-B)
Time frame: Day 15 (Baseline) to Day 18
Change From Baseline in Fasting Plasma Glucose (FPG)
Time frame: 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 Oral Glucose Tolerance Test (OGTT) Area Under the Curve (AUC 0-180): Glucose
Time frame: Day 1 (Baseline) to Day 16
Change From Baseline in Oral Glucose Tolerance Test (OGTT) Area Under the Curve (AUC 0-180): Insulin
Time frame: Day 1 (Baseline) to Day 16
Change From Baseline in Continuous Glucose Monitoring System (CGMS): Time in Ranges
Time frame: 14:00 on Day -1 to 22:00 on Day 1 (Baseline) to 14:00 on Day 15 to 22:00 on Day 16 - omitting data collected between a subject's OGTT glucose consumption start time + 180 minutes
Change From Baseline in Continuous Glucose Monitoring System (CGMS): Average Daily Glucose
Time frame: 14:00 on Day -1 to 22:00 on Day 1 (Baseline) to 14:00 on Day 15 to 22:00 on Day 16 - omitting data collected between a subject's OGTT glucose consumption start time + 180 minutes
Change From Baseline in Continuous Glucose Monitoring System (CGMS): Blood Glucose Coefficient of Variation
Time frame: 14:00 on Day -1 to 22:00 on Day 1 (Baseline) to 14:00 on Day 15 to 22:00 on Day 16 - omitting data collected between a subject's OGTT glucose consumption start time + 180 minutes
Change From Baseline in Continuous Glucose Monitoring System (CGMS): Low/High Blood Glucose Index
Time frame: 14:00 on Day -1 to 22:00 on Day 1 (Baseline) to 14:00 on Day 15 to 22:00 on Day 16 - omitting data collected between a subject's OGTT glucose consumption start time + 180 minutes
Incidence of Adverse Device Effects (ADEs) With a Severity Score of 2: Treatment Emergent Adverse Events (TEAEs) by System Organ Class and Preferred Term
Time frame: Screening to Day 28
Incidence of Adverse Device Effects (ADEs) With a Severity Score of 3: Treatment Emergent Adverse Events (TEAEs) by System Organ Class and Preferred Term
Time frame: Screening to Day 28
Incidence of Adverse Device Effects (ADEs) With a Severity Score of 4: Treatment Emergent Adverse Events (TEAEs) by System Organ Class and Preferred Term
Time frame: Screening to Day 28
Incidence of Adverse Device Effects (ADEs) With a Severity Score of 5: Treatment Emergent Adverse Events (TEAEs) by System Organ Class and Preferred Term
Time frame: Screening to Day 28
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jun 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 9839117Levy 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.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bridgette Boggess Franey, MD principal investigator
ProSciento, Inc.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Hepatic Ultrasound Insonification in people with Type 2 Diabetes, run by General Electric Research at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 35 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Jun 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Glucose Disposal Rate: Insulin Ratio During Steady State (M/I) (time frame: Day 2 (Baseline) to Day 17). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04502212, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jun 2022; AzTrials last refreshed its copy on 7 Nov 2026.