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

Primary Purpose

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

Status

Suspended

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Diazoxide

Placebo

About this trial

This is an interventional basic science trial for Diabetes Mellitus, Type 2 focused on measuring diabetes, type 2 diabetes, insulin resistance, diazoxide, MRI

Eligibility Criteria

21 Years - 70 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Albert Einstein College of Medicine

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Arm Label

Healthy (Diazoxide)

Healthy (Placebo)

T2D (Diazoxide)

T2D (Placebo)

Arm Description

Proglycem, oral suspension (4-7 mg/kg). Healthy participants will receive diazoxide between MRI scans.

Taste-matched placebo. Healthy participants will receive placebo between MRI scans.

Proglycem, oral suspension (4-7 mg/kg). Type 2 diabetic (T2D) participants will receive diazoxide between MRI scans.

Taste-matched placebo. T2D participants will receive placebo between MRI scans.

Outcomes

Primary Outcome Measures

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.

Change in Arterial Spin Labeling (ASL) signal measured using 3T MRI from 2 hours post dosing to 4 hours post dosing

Secondary Outcome Measures

Full Information

NCT ID

NCT03566511

First Posted

May 17, 2018

Last Updated

June 2, 2023

Sponsor

Albert Einstein College of Medicine

Collaborators

National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

1. Study Identification

Unique Protocol Identification Number

NCT03566511

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2023

Overall Recruitment Status

Suspended

Why Stopped

Temporarily paused while the MR center develops newer study techniques. We might resume; this is not a suspension of IRB approval.

Study Start Date

June 12, 2018 (Actual)

Primary Completion Date

August 2024 (Anticipated)

Study Completion Date

August 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Albert Einstein College of Medicine

Collaborators

National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

Keywords

diabetes, type 2 diabetes, insulin resistance, diazoxide, MRI

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 2

Interventional Study Model

Crossover Assignment

Masking

Participant

Masking Description

The subject will be blinded to which study drug is received first (Drug or Placebo).This protocol follows a double blinded, randomized, crossover design.

Allocation

Randomized

Enrollment

24 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Healthy (Diazoxide)

Arm Type

Experimental

Arm Description

Proglycem, oral suspension (4-7 mg/kg). Healthy participants will receive diazoxide between MRI scans.

Arm Title

Healthy (Placebo)

Arm Type

Placebo Comparator

Arm Description

Taste-matched placebo. Healthy participants will receive placebo between MRI scans.

Arm Title

T2D (Diazoxide)

Arm Type

Experimental

Arm Description

Proglycem, oral suspension (4-7 mg/kg). Type 2 diabetic (T2D) participants will receive diazoxide between MRI scans.

Arm Title

T2D (Placebo)

Arm Type

Placebo Comparator

Arm Description

Taste-matched placebo. T2D participants will receive placebo between MRI scans.

Intervention Type

Drug

Intervention Name(s)

Diazoxide

Other Intervention Name(s)

Proglycem

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Healthy and T2D participants will receive placebo between baseline MRI scan and second MRI scan.

Primary Outcome Measure Information:

Title

Change in Arterial Spin Labeling (ASL) signal measured using 3T MRI from Baseline to 2 hours post dosing

Description

Time Frame

Baseline, 2 hours post dosing

Title

Change in Arterial Spin Labeling (ASL) signal measured using 3T MRI from 2 hours post dosing to 4 hours post dosing

Description

Time Frame

2 hours post dosing, 4 hours post dosing

10. Eligibility

Sex

All

Minimum Age & Unit of Time

21 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Meredith Hawkins, M.D., M.S.

Organizational Affiliation

Albert Einstein College of Medicine

Official's Role

Principal Investigator

Facility Information:

Facility Name

Albert Einstein College of Medicine

City

Bronx

State/Province

New York

ZIP/Postal Code

10461

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

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

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