Mechanisms of Ultrasound Neuromodulation Effects in Diabetes

Обзор

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).

Подробное описание

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.

Вмешательства

• Устройство 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.
• Диагностический тест OGTT with unlabeled glucose and liver NMR
  Subjects will undergo an OGTT with unlabeled glucose to measure liver glycogen concentration by NMR spectroscopy.
• Диагностический тест 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.
• Диагностический тест CGM glucose reading
  A continuous glucose monitor (CGM) will be collecting glucose level changes over a 10-14day time period after the ultrasound.
• Диагностический тест HEC - Hyperinsulinemic-Euglycemic-Clamp
  A constant i.v. insulin and variable glucose infusion will be used to determine insulin sensitivity of study participants.

Первичные конечные точки

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

Вторичные конечные точки (6)

• Absolute glycogen level [Срок оценки: during glucose tolerance testing (for 180 minutes).]
• Glycogen synthesis rates [Срок оценки: during glucose tolerance testing (for 180 minutes).]
• Change from baseline in blood glucose (BG) time spent in defined glucose ranges [Срок оценки: 1 week]
• Average daily glucose [Срок оценки: 1 week]
• Low blood glucose index (LBGI) [Срок оценки: 1 week]
• High blood glucose index (HBGI) [Срок оценки: 1 week]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Другое

Центры проведения

США · 1 центр

• Yale School of Medicine — New Haven

Идентификаторы

NCT: NCT06042517 · 2000034954 · 1R01DK131127-01A1

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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