Clinical trial NCT06042517: Mechanisms of Ultrasound Neuromodulation Effects in Diabetes
Official title: Mechanisms of Ultrasound Neuromodulation Effects in Diabetes
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Insulin Sensitivity
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2023-09-18
Enrollment: 77
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: OTHER

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).

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Insulin Sensitivity
timeFrame: Measured during HE clamp.
measure: Glucose disposal rate
timeFrame: Measured during HE clamp.
measure: Glucose metabolic clearance rate
timeFrame: Measured during HE clamp.
Secondary outcomes:
measure: Absolute glycogen level
timeFrame: during glucose tolerance testing (for 180 minutes).
measure: Glycogen synthesis rates
timeFrame: during glucose tolerance testing (for 180 minutes).
measure: Change from baseline in blood glucose (BG) time spent in defined glucose ranges
timeFrame: 1 week
measure: Average daily glucose
timeFrame: 1 week
measure: Low blood glucose index (LBGI)
timeFrame: 1 week
measure: High blood glucose index (HBGI)
timeFrame: 1 week
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale School of Medicine
state: Connecticut
Study officials:
affiliation: Yale University
name: Raimund Herzog, MD, MHS
role: PRINCIPAL_INVESTIGATOR
References: