Use of Functional MRI to Assess Functional Hypothalamic Activation in Response to Diazoxide

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

Use of Functional MRI to Assess Functional Hypothalamic Activation in Response to Diazoxide

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT03566511
• Other study ID #: 2018-9040
• Secondary ID: R01DK069861
• Status: Suspended
• Phase: Phase 2
• Start date: June 12, 2018
• Est. completion date: August 2024

Study information

• Verified date: June 2023
• Source: Albert Einstein College of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this study is to determine whether metabolic control centers in the brain can be activated in patients with type 2 diabetes as compared to non-diabetic individuals. This is important since people with diabetes have inappropriately high production of glucose, which could be at least in part due to impaired activation of important brain centers.

Description:

In this study investigators will use functional magnetic resonance imaging (fMRI), a safe, noninvasive method of measuring brain activity by imaging the blood flow to different parts of the brain, to assess the impact of the medication diazoxide on both diabetic and non-diabetic patients. fMRI is a technique for measuring and mapping brain activity. This technique relies on the fact that cerebral blood flow and neuronal activity are coupled. Previous rodent and human studies have demonstrated that diazoxide activates potassium (KATP) channels that are sensitive to ATP in the hypothalamus, inhibiting hepatic glucose production. However, these inhibitory effects of diazoxide on hepatic glucose production are curiously absent in diabetic patients, which suggests that they may have impaired activation of KATP channels and thus lowered brain activity in this area of the brain. After screening and meeting eligibility criteria, participants will have 2 day-long study visits (one day in which the brain will be imaged before and after receiving diazoxide, and one day in which the brain will be imaged before and after placebo. Each study day will include up to 3 MRI scans per study visit and hourly blood draws.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 24
• Est. completion date: August 2024
• Est. primary completion date: August 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years to 70 Years

Eligibility

Inclusion Criteria:

• Type 2 Diabetes (T2D)
• Age: Between 21 and 70 y.o.
• BMI: <35
• A1c 8.0-12.0%
• Negative drug screen
• Not suffering from proliferative retinopathy, significant diabetic renal disease or severe neuropathy (including cardiovascular and gastrointestinal autonomic dysfunction)
• Healthy (ND)
• Age: Between 21 and 70 y.o.
• BMI: <30
• Negative drug screen
• No family history of diabetes among first-degree relatives (mother, father)

Exclusion Criteria:

• Age: Under 21 or over 70 y.o.
• BMI: >35 for T2D and >30 for ND
• Hypertension
• Severe polydipsia and polyuria
• Uncontrolled hyperlipidemia
• Clinically significant liver dysfunction
• Clinically significant kidney dysfunction
• Anemia
• Clinically significant leukocytosis or leukopenia
• Clinically significant thrombocytopenia or thrombocytosis
• Coagulopathy
• Positive urine drug screen
• Urinalysis: Clinically significant abnormalities
• Clinically significant electrolyte abnormalities
• Smoking >10 cig/day
• Alcohol: Men >14 drinks/wk or > 4 drinks/day, Women >7 drinks/wk or >3 drinks/day
• History of chronic liver disease, active hepatitis infection, HIV/AIDS, chronic kidney disease (stage 3 or greater), active cancer, cardiovascular disease or other heart disease, systemic rheumatologic conditions, seizures, bleeding disorders, muscle disease
• Surgeries that involve removal of endocrine glands except for thyroidectomy
• Pregnant women
• Subject enrolled in another study less than one month prior to the anticipated start date of the proposed study
• Family history: family history of premature cardiac death
• Allergies to medication administered during study
• Uncontrolled psychiatric disorders
• Perimenopausal women who are experiencing/have experienced hot flashes
• Any contraindications for MRI: presence of any non-MRI compatible implants including pacemaker, aneurysm clip, cochlear implant, neurostimulator; history of eye injury with metal; history of ever being a metal worker; history of gunshot wounds or any other imbedded metal objects; history of claustrophobia or prior episodes of significant anxiety or discomfort while obtaining an MRI.
• Any condition which in the opinion of the PI makes the subject ill-suited for participation in the study

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Glucose Metabolism Disorders
• Glucose Metabolism Disorders (Including Diabetes Mellitus)
• Glucose, High Blood
• Metabolic Diseases

Intervention

Drug:
• Diazoxide
Healthy and T2D participants will receive diazoxide at a dose of 4-7 mg/kg (based upon weight) between baseline MRI scan and second MRI scan.
• Placebo
Healthy and T2D participants will receive placebo between baseline MRI scan and second MRI scan.

Locations

Country	Name	City	State
United States	Albert Einstein College of Medicine	Bronx	New York

Sponsors (3)

Lead Sponsor	Collaborator
Albert Einstein College of Medicine	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Arterial Spin Labeling (ASL) signal measured using 3T MRI from Baseline to 2 hours post dosing	ASL is a measure of brain blood flow, and an increase in ASL is interpreted as an increase in brain activity. Data is collected at three time points during each of the two visits (pre dosing, 2 hours post dosing, 4 hours post dosing). Data is compared between Non-Diabetic and Type 2 Diabetic Subjects.	Baseline, 2 hours post dosing
Primary	Change in Arterial Spin Labeling (ASL) signal measured using 3T MRI from 2 hours post dosing to 4 hours post dosing	ASL is a measure of brain blood flow, and an increase in ASL is interpreted as an increase in brain activity. Data is collected at three time points during each of the two visits (pre dosing, 2 hours post dosing, 4 hours post dosing). Data is compared between Non-Diabetic and Type 2 Diabetic Subjects.	2 hours post dosing, 4 hours post dosing