Recruiting

Ultrasound Neuromodulation

Sponsor:

Yale University

Code:

NCT06042517

Conditions

Insulin Sensitivity

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

Ultrasound

OGTT with unlabeled glucose and liver NMR

OGTT with carbon-13 labeled glucose and liver NMR

CGM glucose reading

HEC - Hyperinsulinemic-Euglycemic-Clamp

Study Details

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

Study ID

NCT06042517

Start date

Sep 30, 2023

Status verified date

Aug, 2026

Completion date

Sep 30, 2027

Anticipated

Primary completion date

Sep 30, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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:

1. 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.
2. Be willing to carry a continuous glucose monitor for at least 10 days.
3. Be willing to follow all required instructions by study personnel and appear for the required laboratory assessments, including euglycemic clamps and OGTT.

Exclusion Criteria:

  • 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.

Study Design

Enrollment

77 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Other

Interventions and Outcome Measures

Arms

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

Hepatic ultrasound during a hyperinsulinemic euglycemic clamp (HEC).

experimental: Cohort 2: Ultrasound then NMR with unlabeled glucose.

Hepatic ultrasound and subsequent NMR measurement of glycogen with unlabeled glucose.

experimental: Cohort 3: Ultrasound then NMR with carbon13 labeled glucose.

Hepatic ultrasound and subsequent NMR measurement of glycogen with carbon13 labeled glucose.

experimental: Cohort 4: Dual site ultrasound stimulation followed by CGM glucose recording alone.

Hepatoportal plexus + superior mesenteric plexus dual site ultrasound stimulation followed by CGM glucose recording alone.

Interventions

Ultrasound

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 NMR

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

OGTT with carbon-13 labeled glucose and liver NMR

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

CGM glucose reading

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

HEC - Hyperinsulinemic-Euglycemic-Clamp

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

Primary outcome measure

  • Insulin Sensitivity [ Time Frame: Measured during HE clamp. ]
  • Glucose disposal rate [ Time Frame: Measured during HE clamp. ]
  • Glucose metabolic clearance rate [ Time Frame: Measured during HE clamp. ]

Central Contacts and Locations

Central contacts

Raimund Herzog, MD MHS

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

Locations

Yale School of Medicine

Recruiting

New Haven, Connecticut, United States, 06520

More Information

Sponsor

Yale University

Last update posted

Aug 24, 2026

Last verified

Aug, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Yale University on 2026-08-24.