Insulin SensitivityNCT06042517
Mechanisms of Ultrasound Neuromodulation Effects in Diabetes
A study testing Ultrasound, OGTT with unlabeled glucose and liver NMR and OGTT with carbon-13 labeled glucose and liver NMR in people with Insulin Sensitivity, run by Yale University at 1 site in United States.
Trial summary
This study aims to evaluate the effect of hepatic ultrasound treatment on changes from baseline in whole-body insulin sensitivity during a hyperinsulinemic, euglycemic clamp (HE Clamp). Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Insulin Sensitivity
- What is being tested?
- Ultrasound, OGTT with unlabeled glucose and liver NMR and OGTT with carbon-13 labeled glucose and liver NMR
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 77 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Sep 2023to 30 Sep 2027
- Phase
- Interventional
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 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Type 2 diabetic (T2D) subjects must be aged 18-80 and must be able to provide written informed consent
- All subjects must have had T2D for at least 3 months prior to study enrollment. All subjects must be either on diet and exercise or oral antidiabetic agents alone, not on insulin or any form of insulin or GLP-1 receptor agonists.
- Subjects must demonstrate:
- A past medical history of abnormal glucose control and carry a diagnosis of T2D according to current ADA criteria:
- A fasting plasma glucose (FPG) level of 126 mg/dL (7.0 mmol/L) or higher, or
- A 2-hour plasma glucose level of 200 mg/dL (11.1 mmol/L) or higher during a 75-g oral glucose tolerance test (OGTT), or
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- A random plasma glucose of 200 mg/dL (11.1 mmol/L) or higher in a patient with classic symptoms of hyperglycemia or hyperglycemic crisis or
- A hemoglobin A1c (HbA1c) level of 6.5% or higher.
- Be willing to carry a continuous glucose monitor for at least 10 days.
- Be willing to follow all required instructions by study personnel and appear for the required laboratory assessments, including euglycemic clamps and OGTT.
Who cannot join
- BMI >40kg/m2.
- Untreated proliferative retinopathy
- Creatinine clearance < 60 ml/min/1.73 m2.
- Serum creatinine ≥1.5 mg/dL
- Positive pregnancy test, or presently breast-feeding, or failure to follow effective contraceptive measures
- Active infection including hepatitis C, hepatitis B, HIV,
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- Any history of Active alcohol abuse
- History of non-adherence to prescribed regimens
- Baseline Hgb < 10.5 g/dL in females, or < 13 g/dL in males
- History of coagulopathy or medical condition requiring long-term anticoagulant therapy (low-dose aspirin treatment is allowed)
- Co-existing cardiac disease with active medication titration. Patients on stable meds without active cardiac complications permitted.
- Liver function tests outside of 3xUL of normal range
- GI disorders potentially interfering with the ability to absorb oral medications and h/o upper GI surgery that might have changed anatomy in the target areas.
- Any medical condition or medication that, in the opinion of the investigators, will interfere with the safe completion of the study or study outcomes.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Yale School of Medicine
New Haven, Connecticut, 06520
About this study
This study aims to evaluate the effect of hepatic ultrasound treatment on changes from baseline in whole-body insulin sensitivity during a hyperinsulinemic, euglycemic clamp (HE Clamp).
Read the detailed description
Drop-outs will be replaced; data will be used as much as can be. Subjects will undergo a Screening visit to assess eligibility and will then be scheduled to undergo 2 outpatient US treatment visits.
On day three subjects first undergo a third ultrasound session and then will either undergo Oral Glucose Tolerance Test (OGTT) with carbon13 (13C-glucose) tracer administration and subsequent NMR spectroscopy OR if enrolled into the HEC study arm will undergo euglycemic clamp testing. Following these procedures there will be an approximately two-week follow-up observational Period (with CGM). A two-week washout period will be followed by another cycle of the same procedures of either OGTT/NMR or HEC study, respectively.
- Conditions
- Insulin Sensitivity
- Being tested
- Ultrasound, OGTT with unlabeled glucose and liver NMR, OGTT with carbon-13 labeled glucose and liver NMR, CGM glucose reading, HEC - Hyperinsulinemic-Euglycemic-Clamp
- Medical subject headings
- Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
UltrasoundDevice
The General Electric LOGIQ E10 ultrasound pulsed doppler imaging system and C1-6-D XDclear abdominal curvilinear probe will be used to administer ultrasound.
OGTT with unlabeled glucose and liver NMRDiagnostic test
Subjects will undergo an OGTT with unlabeled glucose to measure liver glycogen concentration by NMR spectroscopy.
OGTT with carbon-13 labeled glucose and liver NMRDiagnostic test
Subjects will undergo an OGTT with carbon-13 labeled glucose to measure liver glycogen synthesis rate by NMR spectroscopy.
CGM glucose readingDiagnostic test
A continuous glucose monitor (CGM) will be collecting glucose level changes over a 10-14day time period after the ultrasound.
HEC - Hyperinsulinemic-Euglycemic-ClampDiagnostic test
A constant i.v. insulin and variable glucose infusion will be used to determine insulin sensitivity of study participants.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: Ultrasound during a hyperinsulinemic euglycemic clamp (HEC). | Experimental | Hepatic ultrasound during a hyperinsulinemic euglycemic clamp (HEC). Receives: Device: Ultrasound; Diagnostic Test: CGM glucose reading; Diagnostic Test: HEC - Hyperinsulinemic-Euglycemic-Clamp |
| Cohort 2: Ultrasound then NMR with unlabeled glucose. | Experimental | Hepatic ultrasound and subsequent NMR measurement of glycogen with unlabeled glucose. Receives: Device: Ultrasound; Diagnostic Test: OGTT with unlabeled glucose and liver NMR; Diagnostic Test: CGM glucose reading |
| Cohort 3: Ultrasound then NMR with carbon13 labeled glucose. | Experimental | Hepatic ultrasound and subsequent NMR measurement of glycogen with carbon13 labeled glucose. Receives: Device: Ultrasound; Diagnostic Test: OGTT with carbon-13 labeled glucose and liver NMR; Diagnostic Test: CGM glucose reading |
| Cohort 4: Dual site ultrasound stimulation followed by CGM glucose recording alone. | Experimental | Hepatoportal plexus + superior mesenteric plexus dual site ultrasound stimulation followed by CGM glucose recording alone. Receives: Device: Ultrasound; Diagnostic Test: CGM glucose reading |
What is being measured
The primary outcome is the main question the study is designed to answer.
Insulin Sensitivity
Insulin Sensitivity calculated as Glucose disposal rate / insulin ratio during steady state (M/I) to evaluate the effect of hepatic ultrasound treatment on changes from baseline in whole-body insulin sensitivity during a hyperinsulinemic, euglycemic clamp (HE Clamp)
Measured: Measured during HE clamp.
Glucose disposal rate
Glucose disposal rate during steady state (M) to evaluate the effect of hepatic ultrasound treatment on changes from baseline in whole-body insulin sensitivity during a hyperinsulinemic, euglycemic clamp (HE Clamp)
Measured: Measured during HE clamp.
Glucose metabolic clearance rate
Glucose metabolic clearance rate during steady state (MCR) to evaluate the effect of hepatic ultrasound treatment on changes from baseline in whole-body insulin sensitivity during a hyperinsulinemic, euglycemic clamp (HE Clamp)
Measured: Measured during HE clamp.
Secondary outcomes (6)
Absolute glycogen level
The effect of hepatic plexus-directed pFUS on absolute glycogen level by observing the metabolic fate of unlabeled glucose ingested during oral glucose tolerance testing measured by 13C liver NMR-spectroscopy.
Measured: during glucose tolerance testing (for 180 minutes).
Glycogen synthesis rates
Glycogen synthesis rates are derived from plasma 13C -glucose levels achieved during the OGTT and subsequent appearance of 13C -tracer in liver glycogen
Measured: during glucose tolerance testing (for 180 minutes).
Change from baseline in blood glucose (BG) time spent in defined glucose ranges
Change from baseline in blood glucose (BG) time spent in defined glucose ranges assessed using a continuous glucose monitoring system (CGMS)
Measured: 1 week
Average daily glucose
Average daily glucose assessed using a continuous glucose monitoring system (CGMS)
Measured: 1 week
Low blood glucose index (LBGI)
Frequency of low glucose events detected during continuous glucose measurement.
Measured: 1 week
High blood glucose index (HBGI)
Frequency of high glucose events detected during continuous glucose measurement.
Measured: 1 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Sep 2023
- Study start30 Sep 2023
- Primary completion30 Sep 2027 (estimated)
- Study completion30 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Insulin SensitivityStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- 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
- Randomised
- Intervention model
- Parallel groups
- Model description
- For Cohort 4: T2DM subjects, age-, BMI- and HbA1c-matched to cohorts 1 and 2 will be recruited from the same pool of volunteers and selected according to the same inclusion and exclusion criteria outlined in the human subject protection plan. 5 additional subjects will be recruited to participate in cohort 3.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 77 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Raimund Herzog, MD, MHS, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06042517
- Sponsor's protocol ID
- 2000034954
- Other IDs
- 1R01DK131127-01A1
- Status last verified
- Aug 2026
- First submitted
- 22 Aug 2023
- Last updated
- 24 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No