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 (T2D) 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.
Brief Title
Use of Functional MRI to Assess Functional Hypothalamic Activation in Response to Diazoxide
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 (CBF) 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.
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.
Completion Date
Completion Date Type
Actual
Conditions
Diabetes Mellitus, Type 2
Glucose, High Blood
Glucose Metabolism Disorders (Including Diabetes Mellitus)
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
* 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
Inclusion 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)
* 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)
Gender
All
Gender Based
false
Keywords
diabetes
type 2 diabetes
insulin resistance
diazoxide
MRI
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
70 Years
Minimum Age
21 Years
NCT Id
NCT03566511
Org Class
Other
Org Full Name
Albert Einstein College of Medicine
Org Study Id
2018-9040
Overall Status
Terminated
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
Use of Functional MRI to Assess Functional Hypothalamic Activation in Response to Diazoxide
Primary Outcomes
Outcome Description
Arterial Spin Labeling data was acquired and converted by the Gruss Magnetic Resonance Research Center (MRRC) and reported as Hypothalamic Cerebral Blood Flow (CBF) which is a more meaningful clinical endpoint measurement. Data was collected at three time points during each of the two study visits (pre dosing, 2 hours post dosing, and 5 hours post dosing). CBF values at the respective timepoints are summarized in mL/100g/min units and reported by study arm. An increase in CBF is correlated with an increase in brain activity.
Outcome Measure
Change in Arterial Spin Labeling (ASL) Signal Measured Using 3T MRI From Baseline to 5 Hours Post Dosing
Outcome Time Frame
2 hours and 5 hours post dosing
Secondary Ids
Secondary Id
R01DK069861
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
70
Minimum Age Number (converted to Years and rounded down)
21
Investigators
Investigator Type
Principal Investigator
Investigator Name
Meredith Hawkins
Investigator Email
meredith.hawkins@einsteinmed.org
Investigator Phone
718-430-3186