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

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ClinicalTrials.gov Identifier: NCT03566511
Recruitment Status : Recruiting
First Posted : June 25, 2018
Last Update Posted : November 18, 2019
Sponsor:
Collaborators:
National Institutes of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Meredith Hawkins, Albert Einstein College of Medicine

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.

Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 2 Glucose, High Blood Glucose Metabolism Disorders (Including Diabetes Mellitus) Drug: Diazoxide Drug: Placebo Phase 2

Detailed Description:

In this study, the investigators will use functional magnetic resonance imaging (fMRI), a method of imaging the blood flow to parts of the brain, to observe the activity of metabolically-relevant areas of the brain by activating Katp channels in healthy participants and in participants with type 2 diabetes (T2D).

All participants will be screened prior to study enrollment. Eligible participants will have 2 day-long study visits (one day in which the brain will be imaged before and after receiving diazoxide (Katp channel activator) 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.

fMRI is a technique for measuring and mapping brain activity that is noninvasive and safe. This technique relies on the fact that cerebral blood flow and neuronal activity are coupled. To assess the effect of diazoxide on activation of hypothalamus and other brain areas in healthy control and T2D subjects, fMRI will be performed at baseline and at 2-hour intervals following administration of diazoxide or placebo.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single (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.
Primary Purpose: Basic Science
Official Title: Use of Functional MRI to Assess Functional Hypothalamic Activation in Response to Diazoxide
Actual Study Start Date : June 12, 2018
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Diazoxide

Arm Intervention/treatment
Experimental: Healthy (Diazoxide)
Proglycem, oral suspension (4-7 mg/kg). Healthy participants will receive diazoxide between MRI scans.
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.
Other Name: Proglycem

Placebo Comparator: Healthy (Placebo)
Taste-matched placebo. Healthy participants will receive placebo between MRI scans.
Drug: Placebo
Healthy and T2D participants will receive placebo between baseline MRI scan and second MRI scan.

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

Placebo Comparator: T2D (Placebo)
Taste-matched placebo. T2D participants will receive placebo between MRI scans.
Drug: Placebo
Healthy and T2D participants will receive placebo between baseline MRI scan and second MRI scan.




Primary Outcome Measures :
  1. Change in Arterial Spin Labeling (ASL) signal measured using 3T MRI from Baseline to 2 hours post dosing [ Time Frame: Baseline, 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.

  2. Change in Arterial Spin Labeling (ASL) signal measured using 3T MRI from 2 hours post dosing to 4 hours post dosing [ Time Frame: 2 hours post dosing, 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.



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Ages Eligible for Study:   21 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03566511


Contacts
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Contact: Matthew Zhao, B.S. 718-430-2903 matthew.zhao@einstein.yu.edu

Locations
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United States, New York
Albert Einstein College of Medicine Recruiting
Bronx, New York, United States, 10461
Contact: Tulsi Patel    718-430-2903    tulsi.patel@einstein.yu.edu   
Principal Investigator: Meredith Hawkins, M.D., M.S.         
Sponsors and Collaborators
Albert Einstein College of Medicine
National Institutes of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
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Principal Investigator: Meredith Hawkins, M.D., M.S. Albert Einstein College of Medicine

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Responsible Party: Meredith Hawkins, Principal Investigator, Albert Einstein College of Medicine
ClinicalTrials.gov Identifier: NCT03566511     History of Changes
Other Study ID Numbers: 2018-9040
R01DK069861 ( U.S. NIH Grant/Contract )
First Posted: June 25, 2018    Key Record Dates
Last Update Posted: November 18, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Meredith Hawkins, Albert Einstein College of Medicine:
diabetes
type 2 diabetes
insulin resistance
diazoxide
MRI
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Metabolic Diseases
Glucose Metabolism Disorders
Hyperglycemia
Endocrine System Diseases
Diazoxide
Antihypertensive Agents
Vasodilator Agents