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| ID | Type | Description | Link |
|---|---|---|---|
| R01DK069861 | U.S. NIH Grant/Contract | View source |
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Grant funding ended. NIDDK grant renewed without an MR aim. No plans to do future studies.
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| Name | Class |
|---|---|
| National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | NIH |
| American Diabetes Association | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Healthy (Diazoxide) | Experimental | Proglycem, oral suspension (4-7 mg/kg). Healthy participants will receive diazoxide between MRI scans. |
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| Healthy (Placebo) | Placebo Comparator | Taste-matched placebo. Healthy participants will receive placebo between MRI scans. |
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| T2D (Diazoxide) | Experimental | Proglycem, oral suspension (4-7 mg/kg). Type 2 diabetic (T2D) participants will receive diazoxide between MRI scans. |
|
| T2D (Placebo) | Placebo Comparator | Taste-matched placebo. T2D participants will receive placebo between MRI scans. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Diazoxide | Drug | 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. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Arterial Spin Labeling (ASL) Signal Measured Using 3T MRI From Baseline to 5 Hours Post Dosing | 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. | 2 hours and 5 hours post dosing |
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Inclusion Criteria:
Type 2 Diabetes (T2D)
Healthy (ND)
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Meredith Hawkins, M.D., M.S. | Albert Einstein College of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Albert Einstein College of Medicine | The Bronx | New York | 10461 | United States |
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37 patients signed consent and were screened for eligibility. Following screening, 22 patients were deemed eligible. Of the 22, 11 did not enroll in the study after passing the screening for various reasons including being lost to follow-up or unable to commit. In summary, 11 patients were enrolled and randomized into the study; however, randomization order cannot be verified from documentation for 3 study patients. These 3 patients did not complete the overall study and were never unblinded.
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| ID | Title | Description |
|---|---|---|
| FG000 | Diazoxide First Then Matched Placebo | Proglycem, oral suspension (4-7 mg/kg). Healthy participants will receive Diazoxide between MRI scans. Diazoxide: Healthy participants will receive Diazoxide at a dose of 4-7 mg/kg (based upon body weight) between baseline MRI scan and second MRI scan. Matched placebo: Healthy participants will receive placebo between baseline MRI scan and second MRI scan. |
| FG001 | Matched Placebo First Then Diazoxide | Proglycem, oral suspension (4-7 mg/kg). T2D participants will receive Diazoxide between MRI scans. Diazoxide: T2D participants will receive Diazoxide at a dose of 4-7 mg/kg (based upon body weight) between baseline MRI scan and second MRI scan. Matched placebo: T2D participants will receive placebo between baseline MRI scan and second MRI scan. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1st Intervention (1 Day) |
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| Washout (~1 Month) |
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| 2nd Intervention (1 Day) |
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As described in the 'Participant Flow' module, 11 patients were enrolled and randomized into the study; however, randomization order could not be verified from documentation for 3 of the study patients. These 3 patients did not complete the overall study and were never unblinded.
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| ID | Title | Description |
|---|---|---|
| BG000 | All Study Participants | Proglycem, oral suspension (4-7 mg/kg). Healthy participants will receive Diazoxide between MRI scans. Diazoxide: Participants will receive Diazoxide at a dose of 4-7 mg/kg (based upon body weight) between baseline MRI scan and second MRI scan. Participants will receive placebo between baseline MRI scan and second MRI scan. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Arterial Spin Labeling (ASL) Signal Measured Using 3T MRI From Baseline to 5 Hours Post Dosing | 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. | 7 patients were able to complete both studies within the crossover design as described in the 'Participant Flow' module and have their data analyzed. An additional 4 patients (3 healthy, and 1 T2D) were not able to complete their measurements and, therefore, no data are available for these patients. Standard error (SE) data for the DZX studies were derived from visual estimates of the bar graphs. SE data for the Placebo studies were extrapolated from DZX studies. | Posted | Mean | Standard Error | mL/100g/min | 2 hours and 5 hours post dosing |
Two, 8-hour visits, up to one month apart
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Diazoxide | Proglycem, oral suspension (4-7 mg/kg). Healthy participants will receive Diazoxide between MRI scans. Diazoxide: Participants will receive Diazoxide at a dose of 4-7 mg/kg (based upon body weight) between baseline MRI scan and second MRI scan. Matched placebo: Participants will receive placebo between baseline MRI scan and second MRI scan. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Uncomfortable | General disorders | Non-systematic Assessment | Verbatim Term: Patient felt "hot and tired" inside the MRI machine. |
Instrumentation got remodeled and further studies were unable to be conducted and the trial was unable to be completed as proposed.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Meredith Hawkins | Albert Einstein College of Medicine | 718-839-7975 | meredith.hawkins@einsteinmed.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jun 2, 2021 | Oct 2, 2024 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Apr 22, 2020 | Oct 2, 2024 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| D044882 | Glucose Metabolism Disorders |
| D003920 | Diabetes Mellitus |
| D007333 | Insulin Resistance |
| ID | Term |
|---|---|
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
| D006946 | Hyperinsulinism |
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| ID | Term |
|---|---|
| D003981 | Diazoxide |
| ID | Term |
|---|---|
| D001581 | Benzothiadiazines |
| D013449 | Sulfonamides |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
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Study was initially intended to be a double blinded, randomized, crossover design; however, it was terminated early due to issues with magnetic resonance (MR) system.
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The subject will be blinded to which study drug is received first (Drug or Placebo).
|
| Placebo | Drug | Healthy and T2D participants will receive placebo between baseline MRI scan and second MRI scan. |
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| NOT COMPLETED |
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| NOT COMPLETED |
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| Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
|
| ID |
|---|
| Title |
|---|
| Description |
|---|
| OG000 | Diazoxide | Proglycem, oral suspension (4-7 mg/kg). Healthy participants will receive Diazoxide between MRI scans. Diazoxide: Participants will receive Diazoxide at a dose of 4-7 mg/kg (based upon body weight) between baseline MRI scan and second MRI scan. Matched placebo: Participants will receive placebo between baseline MRI scan and second MRI scan. |
| OG001 | Matched Placebo | Proglycem, oral suspension (4-7 mg/kg). T2D participants will receive Diazoxide between MRI scans. Diazoxide: Participants will receive Diazoxide at a dose of 4-7 mg/kg (based upon body weight) between baseline MRI scan and second MRI scan. Matched placebo: Participants will receive placebo between baseline MRI scan and second MRI scan. |
|
|
| 0 |
| 7 |
| 0 |
| 7 |
| 0 |
| 7 |
| EG001 | Matched Placebo | Proglycem, oral suspension (4-7 mg/kg). T2D participants will receive Diazoxide between MRI scans. Diazoxide: Participants will receive Diazoxide at a dose of 4-7 mg/kg (based upon body weight) between baseline MRI scan and second MRI scan. Matched placebo: Participants will receive placebo between baseline MRI scan and second MRI scan. | 0 | 7 | 0 | 7 | 1 | 7 |
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| D009930 |
| Organic Chemicals |
| D049971 | Thiazides |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |