Regulation of Endogenous Glucose Production by Central KATP Channels
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ClinicalTrials.gov Identifier: NCT03540758 |
Recruitment Status :
Suspended
(Temporarily paused due to COVID-19 and expected to resume. This is not a suspension of IRB approval.)
First Posted : May 30, 2018
Last Update Posted : January 14, 2021
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Type 2 diabetes affects the ability of the body to process glucose (sugar). Under fasting conditions, the liver is able to make sugar to maintain glucose levels in an important process called endogenous glucose production (EGP). Previous studies suggest that the central nervous system (CNS), including the brain, helps to regulate levels of glucose in the body by communicating with the liver. This process can be impaired in people with type 2 diabetes, and can contribute to the high level of glucose seen in these individuals.
The purpose of this study is to understand how activating control centers of the brain with a medication called diazoxide can affect how much glucose (sugar) is made by the liver. This is particularly important for people with diabetes who have very high production of glucose, which in turn can lead to diabetes complications.
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Type 2 Diabetes Mellitus Glucose Metabolism Disorders Glucose, High Blood | Drug: Diazoxide Drug: Nicotinic acid Drug: Placebo | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 45 participants |
Allocation: | Randomized |
Intervention Model: | Crossover Assignment |
Intervention Model Description: | In Aim 1, non-diabetic participants will be studied after receiving diazoxide or placebo in a randomized, single-blinded fashion. In Aim 2, participants with type 2 diabetes will be studies after receiving diazoxide or placebo in a randomized, single-blinded fashion. In Aim 3, participants with type 2 diabetes will be studied after receiving diazoxide or placebo in a randomized, single-blinded fashion after lowering their free fatty acid levels. |
Masking: | Single (Participant) |
Masking Description: | The subject will be blinded as to which study drug he/she is receiving first (Drug or Placebo). |
Primary Purpose: | Basic Science |
Official Title: | Regulation of Endogenous Glucose Production by Central KATP Channels |
Actual Study Start Date : | August 1, 2018 |
Estimated Primary Completion Date : | April 2022 |
Estimated Study Completion Date : | April 2022 |

Arm | Intervention/treatment |
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Experimental: Non-diabetic (Diazoxide)
Pancreatic clamp study will be done after giving Diazoxide (Proglycem) oral suspension to non-diabetic participants.
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Drug: Diazoxide
Non-diabetic participants will receive diazoxide at a dose of 4-7 mg/kg (based upon weight) before undergoing the pancreatic clamp study. T2D participants will have their blood sugar levels normalized, and will then receive diazoxide at a dose of 4-7 mg/kg (based upon weight) before undergoing the pancreatic clamp study. Other Name: Proglycem |
Placebo Comparator: Non-diabetic (Placebo)
Pancreatic clamp study will be done after giving a taste-matched placebo for Diazoxide (Proglycem) to non-diabetic participants.
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Drug: Placebo
Non-diabetic participants will receive placebo and undergo the pancreatic clamp study. T2D participants will have their blood sugar levels normalized, and will then receive a taste-matched placebo for diazoxide before undergoing the pancreatic clamp study. |
Experimental: T2D (Diazoxide)
Pancreatic clamp study will be done after giving Diazoxide (Proglycem) oral suspension to type 2 diabetic participants.
|
Drug: Diazoxide
Non-diabetic participants will receive diazoxide at a dose of 4-7 mg/kg (based upon weight) before undergoing the pancreatic clamp study. T2D participants will have their blood sugar levels normalized, and will then receive diazoxide at a dose of 4-7 mg/kg (based upon weight) before undergoing the pancreatic clamp study. Other Name: Proglycem |
Placebo Comparator: T2D (Placebo)
Pancreatic clamp study will be done after giving a taste-matched placebo for Diazoxide (Proglycem) to type 2 diabetic participants.
|
Drug: Placebo
Non-diabetic participants will receive placebo and undergo the pancreatic clamp study. T2D participants will have their blood sugar levels normalized, and will then receive a taste-matched placebo for diazoxide before undergoing the pancreatic clamp study. |
Experimental: T2D (Diazoxide + Nicotinic Acid)
Pancreatic clamp study will be done after giving Diazoxide (Proglycem) oral suspension to type 2 diabetic participants after lowering free fatty acids with a nicotinic acid (Niacin) infusion.
|
Drug: Diazoxide
Non-diabetic participants will receive diazoxide at a dose of 4-7 mg/kg (based upon weight) before undergoing the pancreatic clamp study. T2D participants will have their blood sugar levels normalized, and will then receive diazoxide at a dose of 4-7 mg/kg (based upon weight) before undergoing the pancreatic clamp study. Other Name: Proglycem Drug: Nicotinic acid T2D participants will have their blood sugar levels normalized and will additionally receive nicotinic acid infusion based on weight (0.01 mg/kg/min) to lower free fatty acid levels before undergoing the pancreatic clamp study.
Other Name: Niacin |
Experimental: T2D (Nicotinic Acid + placebo for diazoxide)
Pancreatic clamp study will be done after lowering free fatty acids with a nicotinic acid (Niacin) infusion in type 2 diabetic participants, and after giving a taste-matched placebo for Diazoxide (Proglycem) to type 2 diabetic participants.
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Drug: Nicotinic acid
T2D participants will have their blood sugar levels normalized and will additionally receive nicotinic acid infusion based on weight (0.01 mg/kg/min) to lower free fatty acid levels before undergoing the pancreatic clamp study.
Other Name: Niacin Drug: Placebo Non-diabetic participants will receive placebo and undergo the pancreatic clamp study. T2D participants will have their blood sugar levels normalized, and will then receive a taste-matched placebo for diazoxide before undergoing the pancreatic clamp study. |
- Endogenous glucose production (EGP) [ Time Frame: 7-7.5 hours ]Rates of EGP (a measure of the body's production of sugar) will be measured using analysis of blood samples taken throughout the pancreatic clamp procedure under various treatment conditions (eg, placebo, diazoxide, nicotinic acid, nicotinic acid/diazoxide), by monitoring changes in the level of a non-radioactive, naturally occurring form of glucose (sugar).

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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 |
Inclusion Criteria:
For healthy participants:
- Age: 21-70 y.o.
- BMI under 35
- Negative drug screen
- Normal A1C and fasting glucose
- No family history of diabetes among first degree relatives (eg. mother, father)
For T2D participants:
- Age: 21-70 y.o.
- BMI under 35
- A1c 8.0-12.0%
- Negative drug screen
- Not suffering from a previously diagnosed proliferative retinopathy, significant diabetic renal disease or severe neuropathy (including cardiovascular and gastrointestinal autonomic dysfunction).
Exclusion Criteria:
- Age: Under 21 or over 70 y.o.
- BMI: >35
- Blood pressure >150/90 or <90/60 on more than one occasion
- Severe polydipsia and polyuria
- Urine microalbumin: >300 mg/g of creatinine (in subjects with T2D)
- Uncontrolled hyperlipidemia
- Clinically significant liver dysfunction
- Clinically significant kidney dysfunction
- Clinically significant 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, besides those done by our group
- Family history: family history of premature cardiac death
- Allergies to medication administered during study
- Uncontrolled psychiatric disorders
- Any condition which in the opinion of the PI makes the subject ill suited for participation in the study

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): NCT03540758
United States, New York | |
Albert Einstein College of Medicine | |
Bronx, New York, United States, 10461 |
Principal Investigator: | Meredith Hawkins, M.D., M.S. | Albert Einstein College of Medicine |
Responsible Party: | Meredith Hawkins, Principal Investigator, Albert Einstein College of Medicine |
ClinicalTrials.gov Identifier: | NCT03540758 |
Other Study ID Numbers: |
2018-9039 R01DK069861 ( U.S. NIH Grant/Contract ) |
First Posted: | May 30, 2018 Key Record Dates |
Last Update Posted: | January 14, 2021 |
Last Verified: | January 2021 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
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.: | No |
type 2 diabetes diabetes insulin resistance diazoxide |
Diabetes Mellitus, Type 2 Metabolic Diseases Glucose Metabolism Disorders Hyperglycemia Diabetes Mellitus Endocrine System Diseases Niacin Nicotinic Acids Niacinamide Diazoxide Hypolipidemic Agents |
Antimetabolites Molecular Mechanisms of Pharmacological Action Lipid Regulating Agents Vasodilator Agents Vitamin B Complex Vitamins Micronutrients Nutrients Growth Substances Physiological Effects of Drugs Antihypertensive Agents |