Mechanisms of Ultrasound Neuromodulation Effects in Diabetes

Insulin Sensitivity Clinical Trial

Official title:

Mechanisms of Ultrasound Neuromodulation Effects in Diabetes

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06042517
• Other study ID #: 2000034954
• Secondary ID: 1R01DK131127-01A
• Status: Recruiting
• Phase: N/A
• Start date: September 30, 2023
• Est. completion date: September 30, 2027

Study information

• Verified date: January 2024
• Source: Yale University
• Contact: Raimund Herzog, MD MHS
• Phone: +1 (203) 737-4773
• Email: raimund.herzog[@]yale.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 77
• Est. completion date: September 30, 2027
• Est. primary completion date: September 30, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Insulin Resistance
• Insulin Sensitivity

Intervention

Device:
• 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.

Diagnostic Test:
• 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.

Locations

Country	Name	City	State
United States	Yale School of Medicine	New Haven	Connecticut

Sponsors (2)

Lead Sponsor	Collaborator
Yale University	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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.
Primary	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	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.	during glucose tolerance testing (for 180 minutes).
Secondary	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	during glucose tolerance testing (for 180 minutes).
Secondary	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)	1 week
Secondary	Average daily glucose	Average daily glucose assessed using a continuous glucose monitoring system (CGMS)	1 week
Secondary	Low blood glucose index (LBGI)	Frequency of low glucose events detected during continuous glucose measurement.	1 week
Secondary	High blood glucose index (HBGI)	Frequency of high glucose events detected during continuous glucose measurement.	1 week