Diabetes Mellitus, Type 2Phase 2NCT03566511
Use of Functional MRI to Assess Functional Hypothalamic Activation in Response to Diazoxide
A Phase 2 study testing Diazoxide in people with Diabetes Mellitus, Type 2 and Glucose, High Blood, run by Meredith Hawkins at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Diabetes Mellitus, Type 2, Glucose, High Blood, Glucose Metabolism Disorders (Including Diabetes Mellitus)
- What is being tested?
- Diazoxide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 37 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Jun 2018to 1 Aug 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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)
Show all 11Show fewer
- 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)
Who cannot join
- 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
Show all 26Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Albert Einstein College of Medicine
The Bronx, New York, 10461
About this study
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.
Read the 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.
- Conditions
- Diabetes Mellitus, Type 2, Glucose, High Blood, Glucose Metabolism Disorders (Including Diabetes Mellitus)
- Being tested
- Diazoxide, Placebo
- Keywords
- diabetes, type 2 diabetes, insulin resistance, diazoxide, MRI
- Medical subject headings
- Diabetes Mellitus, Type 2, Glucose Metabolism Disorders, Diabetes Mellitus, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DiazoxideDrug
Also called Proglycem
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.
PlaceboDrug
Healthy and T2D participants will receive placebo between baseline MRI scan and second MRI scan.
| Study group | Role | What they receive |
|---|---|---|
| Healthy (Diazoxide) | Experimental | Proglycem, oral suspension (4-7 mg/kg). Healthy participants will receive diazoxide between MRI scans. Receives: Drug: Diazoxide |
| Healthy (Placebo) | Placebo comparator | Taste-matched placebo. Healthy participants will receive placebo between MRI scans. Receives: Drug: Placebo |
| T2D (Diazoxide) | Experimental | Proglycem, oral suspension (4-7 mg/kg). Type 2 diabetic (T2D) participants will receive diazoxide between MRI scans. Receives: Drug: Diazoxide |
| T2D (Placebo) | Placebo comparator | Taste-matched placebo. T2D participants will receive placebo between MRI scans. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 2 hours and 5 hours post dosing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2018
- Study start12 Jun 2018
- Primary completion1 Aug 2020
- Study completion1 Aug 2020
Why it stopped: Grant funding ended. NIDDK grant renewed without an MR aim. No plans to do future studies.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- 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.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- Meredith Hawkins
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), American Diabetes Association
- Responsible party
- Sponsor-investigator, Meredith Hawkins, Albert Einstein College of Medicine
- Investigators
- Meredith Hawkins, M.D., M.S., Principal investigator, Albert Einstein College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03566511
- Sponsor's protocol ID
- 2018-9040
- Other IDs
- R01DK069861
- Status last verified
- May 2025
- First submitted
- 17 May 2018
- Last updated
- 31 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Use of Functional MRI to Assess Functional Hypothalamic Activation in Response to Diazoxide
- ClinicalTrials.gov ID
- NCT03566511
- Acronym / sponsor ID
- 2018-9040
- Conditions
- Diabetes Mellitus, Type 2, Glucose, High Blood, Glucose Metabolism Disorders (Including Diabetes Mellitus)
- Keywords
- diabetes, type 2 diabetes, insulin resistance, diazoxide, MRI
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Grant funding ended. NIDDK grant renewed without an MR aim. No plans to do future studies.
- Enrolment
- 37 participants (actual)
- Lead sponsor
- Meredith HawkinsUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), American Diabetes Association
- Study start
- 12 Jun 2018 (actual)
- Primary completion
- 1 Aug 2020 (actual)
- Study completion
- 1 Aug 2020 (actual)
- First posted
- 25 Jun 2018 (actual)
- Results
- Posted 31 May 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 4
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Healthy (Diazoxide) | Experimental | Drug: DiazoxideProglycem, oral suspension (4-7 mg/kg). Healthy participants will receive diazoxide between MRI scans. |
| Healthy (Placebo) | Placebo comparator | Drug: PlaceboTaste-matched placebo. Healthy participants will receive placebo between MRI scans. |
| T2D (Diazoxide) | Experimental | Drug: DiazoxideProglycem, oral suspension (4-7 mg/kg). Type 2 diabetic (T2D) participants will receive diazoxide between MRI scans. |
| T2D (Placebo) | Placebo comparator | Drug: PlaceboTaste-matched placebo. T2D participants will receive placebo between MRI scans. |
Who may qualify
- Ages
- 21 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Type 2 Diabetes (T2D)
- Healthy (ND)
Key exclusion criteria (26 listed)
- Age: Under 21 or over 70 y.o.
- BMI: >35 for T2D and >30 for ND
- Hypertension
- Severe polydipsia and polyuria
- Uncontrolled hyperlipidemia
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DiazoxideAlso: ProglycemHealthy 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. | Drug | Healthy (Diazoxide), T2D (Diazoxide) |
| PlaceboHealthy and T2D participants will receive placebo between baseline MRI scan and second MRI scan. | Drug | Healthy (Placebo), T2D (Placebo) |
Primary outcome
Change in Arterial Spin Labeling (ASL) Signal Measured Using 3T MRI From Baseline to 5 Hours Post Dosing
Time frame: 2 hours and 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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Meredith Hawkins, M.D., M.S. principal investigator
Albert Einstein College of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Diazoxide in people with Diabetes Mellitus, Type 2 and Glucose, High Blood, run by Meredith Hawkins at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 31 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 31 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Arterial Spin Labeling (ASL) Signal Measured Using 3T MRI From Baseline to 5 Hours Post Dosing (time frame: 2 hours and 5 hours post dosing). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 May 2025.