Mechanisms of Ultrasound Neuromodulation Effects in Diabetes

NCT06042517 | Recruiting DMC FDA Device

• 2 other identifiers: 20000349541R01DK131127-01A1
• Study Type: interventional
• Target: 77
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Insulin Sensitivity

Outcome Measures

Primary Outcomes (3)

• 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 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 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 during HE clamp.

Secondary Outcomes (6)

• Absolute glycogen level

  during glucose tolerance testing (for 180 minutes).

• Glycogen synthesis rates

  during glucose tolerance testing (for 180 minutes).

• Change from baseline in blood glucose (BG) time spent in defined glucose ranges

  1 week

• Average daily glucose

  1 week

• Low blood glucose index (LBGI)

  1 week

Study Arms (4)

Cohort 1: Ultrasound during a hyperinsulinemic euglycemic clamp (HEC).

EXPERIMENTAL

Hepatic ultrasound during a hyperinsulinemic euglycemic clamp (HEC).

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.

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.

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.

Device: Ultrasound; Diagnostic Test: CGM glucose reading

Interventions

Ultrasound DEVICE

The General Electric LOGIQ E10 ultrasound pulsed doppler imaging system and C1-6-D XDclear abdominal curvilinear probe will be used to administer ultrasound.

Cohort 1: Ultrasound during a hyperinsulinemic euglycemic clamp (HEC).; Cohort 2: Ultrasound then NMR with unlabeled glucose.; Cohort 3: Ultrasound then NMR with carbon13 labeled glucose.; Cohort 4: Dual site ultrasound stimulation followed by CGM glucose recording alone.

OGTT with unlabeled glucose and liver NMR DIAGNOSTIC_TEST

Subjects will undergo an OGTT with unlabeled glucose to measure liver glycogen concentration by NMR spectroscopy.

Cohort 2: Ultrasound then NMR with unlabeled glucose.

OGTT with carbon-13 labeled glucose and liver NMR DIAGNOSTIC_TEST

Subjects will undergo an OGTT with carbon-13 labeled glucose to measure liver glycogen synthesis rate by NMR spectroscopy.

Cohort 3: Ultrasound then NMR with carbon13 labeled glucose.

CGM glucose reading DIAGNOSTIC_TEST

A continuous glucose monitor (CGM) will be collecting glucose level changes over a 10-14day time period after the ultrasound.

Cohort 1: Ultrasound during a hyperinsulinemic euglycemic clamp (HEC).; Cohort 2: Ultrasound then NMR with unlabeled glucose.; Cohort 3: Ultrasound then NMR with carbon13 labeled glucose.; Cohort 4: Dual site ultrasound stimulation followed by CGM glucose recording alone.

HEC - Hyperinsulinemic-Euglycemic-Clamp DIAGNOSTIC_TEST

A constant i.v. insulin and variable glucose infusion will be used to determine insulin sensitivity of study participants.

Cohort 1: Ultrasound during a hyperinsulinemic euglycemic clamp (HEC).

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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,
• 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.

Sponsors & Collaborators

• Yale University: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Yale School of Medicine

New Haven, Connecticut, 06520, United States

RECRUITING

MeSH Terms

Conditions

Insulin Resistance

Interventions

Ultrasonography; Glucose Tolerance Test

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Blood Chemical Analysis; Clinical Chemistry Tests; Clinical Laboratory Techniques; Diagnostic Techniques, Endocrine; Investigative Techniques

Study Officials

• Raimund Herzog, MD, MHS

  Yale University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Raimund Herzog, MD MHS

CONTACT

+1 (203) 737-4773; raimund.herzog@yale.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: August 22, 2023
• First Posted: September 18, 2023
• Study Start: September 30, 2023
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): September 30, 2027
• Last Updated: May 8, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)