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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

Tracking Information
First Submitted Date  ICMJE May 17, 2018
First Posted Date  ICMJE June 25, 2018
Last Update Posted Date November 18, 2019
Actual Study Start Date  ICMJE June 12, 2018
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 13, 2019)
  • 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.
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: June 12, 2018)
  • Change in Blood Oxygenation Level Dependent (BOLD EPI) signal measured using 3 Tesla MRI from Baseline to 2 hours post dosing [ Time Frame: Baseline, 2 hours post dosing ]
    BOLD EPI is a measure of brain blood flow, and an increase in BOLD EPI is interpreted as increases in brain activity. The overall study consists of a total of two visits to the clinic. 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 Blood Oxygenation Level Dependent (BOLD EPI) signal measured using 3 Tesla MRI from 2 hours post dosing to 4 hours post dosing [ Time Frame: 2 hours post dosing, 4 hours post dosing ]
    BOLD EPI is a measure of brain blood flow, and an increase in BOLD EPI is interpreted as increases in brain activity. The overall study consists of a total of two visits to the clinic. 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 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.
  • 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.
Change History Complete list of historical versions of study NCT03566511 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Use of Functional MRI to Assess Functional Hypothalamic Activation in Response to Diazoxide
Official Title  ICMJE Use of Functional MRI to Assess Functional Hypothalamic Activation in Response to Diazoxide
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, 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE 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
Condition  ICMJE
  • Diabetes Mellitus, Type 2
  • Glucose, High Blood
  • Glucose Metabolism Disorders (Including Diabetes Mellitus)
Intervention  ICMJE
  • 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
  • Drug: Placebo
    Healthy and T2D participants will receive placebo between baseline MRI scan and second MRI scan.
Study Arms  ICMJE
  • Experimental: Healthy (Diazoxide)
    Proglycem, oral suspension (4-7 mg/kg). Healthy participants will receive diazoxide between MRI scans.
    Intervention: Drug: Diazoxide
  • Placebo Comparator: Healthy (Placebo)
    Taste-matched placebo. Healthy participants will receive placebo between MRI scans.
    Intervention: Drug: Placebo
  • Experimental: T2D (Diazoxide)
    Proglycem, oral suspension (4-7 mg/kg). Type 2 diabetic (T2D) participants will receive diazoxide between MRI scans.
    Intervention: Drug: Diazoxide
  • Placebo Comparator: T2D (Placebo)
    Taste-matched placebo. T2D participants will receive placebo between MRI scans.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 12, 2018)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2021
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Matthew Zhao, B.S. 718-430-2903 matthew.zhao@einstein.yu.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03566511
Other Study ID Numbers  ICMJE 2018-9040
R01DK069861 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Meredith Hawkins, Albert Einstein College of Medicine
Study Sponsor  ICMJE Albert Einstein College of Medicine
Collaborators  ICMJE
  • National Institutes of Health (NIH)
  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators  ICMJE
Principal Investigator: Meredith Hawkins, M.D., M.S. Albert Einstein College of Medicine
PRS Account Albert Einstein College of Medicine
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP