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Diabetes MellitusPhase 2NCT03540758

Regulation of Endogenous Glucose Production by Central KATP Channels

A Phase 2 study testing Diazoxide and Nicotinic acid in people with Diabetes Mellitus and Glucose Metabolism Disorders, run by Albert Einstein College of Medicine at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

Type 2 diabetes (T2D) 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). Read more about this study

Who is it for?
Ages 21 to 70 yearsHealthy volunteers can take part
What is being tested?
Diazoxide and Nicotinic acid
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
100 participants
Where
1 siteUnited States
Study dates
1 Aug 2018to Apr 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

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

  • For healthy (non-diabetic) participants:
  • Age: 21-70 years old
  • Body Mass Index (BMI) under 40 kg/m^2
  • Negative drug screen (see below)
  • Normal Hemoglobin A1c (HbA1c) and fasting glucose
  • In general good health (see below for exclusions)
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  • Not participating in any other research study besides those done by the study team
  • For T2D participants:
  • Age: 21-70 years old
  • BMI under 40 kg/m^2
  • Stable and moderate-to-poor glycemic control (HbA1c: 8.0-12.0%)
  • Negative drug screen (see below)
  • Not suffering from a previously diagnosed proliferative retinopathy, significant diabetic renal disease (urinary microalbumin <100 μg/dl) or severe peripheral neuropathy (including cardiovascular and gastrointestinal autonomic neuropathy) per medical history
  • Diabetic subjects will be otherwise in good health (see below for exclusions), taking no medications that might affect study eligibility based on review by study doctor, and not participating in any other research study besides those done by the study team

Who cannot join

  • Age: Under 21 or over 70 years old
  • BMI: >40 kg/m^2 for Type 2 Diabetes (T2D) and Non-Diabetic (ND) subjects
  • Blood pressure >150/90 or <90/60 on more than one occasion
  • Severe polydipsia and polyuria (in subjects with T2D). Since polydipsia and polyuria are common symptoms of T2D, the distinction "severe" denotes that the subject indicates a worsening in the symptoms and/or an experience of discomfort related to the symptoms at the time of screening and/or at the time of withdrawal from the medications
  • Urine microalbumin: >300 mg/g of creatinine (in subjects with T2D)
  • Uncontrolled hyperlipidemia defined as Triglycerides (TG) > 400 mg/dL and/or Total Cholesterol >300 mg/dL
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  • Clinically significant liver dysfunction including thrombocytopenia (platelets <100,000/uL), anemia (as below), hypoalbuminemia (<3.5 g/dL), coagulopathy (INR > 1.5), and/or liver enzymes more than 3 times the upper limit of normal
  • Clinically significant kidney dysfunction, Glomerular Filtration Rate (GFR): <60 mg/dL
  • Clinically significant anemia. Prospective subjects with hemoglobin below the lower limit of 12 g/dl for for men and 11 g/dL for women will be assessed with history and physical exam to rule out clinically significant anemia, defined as an individual with symptoms (e.g., fatigue, weakness, shortness of breath, palpitations), signs (pallor, brittle nails etc.), or currently under treatment for anemia. In the absence of a documented hemoglobin decrease or iron deficiency, subjects will not be excluded
  • Clinically significant leukocytosis or leukopenia
  • Clinically significant thrombocytopenia or thrombocytosis
  • Coagulopathy
  • Urine drug screen positive for any of the following: amphetamines, barbiturates, benzodiazepines, cocaine, methadone, opiates, oxycodone, phencyclidine (PCP). Amphetamines, oxycodone, opiates, methadone, and benzodiazepines have been shown to affect glucose metabolism (increased glycemia, increased fasting insulin levels, delayed insulin response to food ingestion, insulin deficiency). As the drug test available in the Clinical Research Center (CRC) is a 7-drug panel, the investigator team cannot specifically choose which drugs are screened for. Additionally, in the interest of selecting patients on the basis of their reliability and dependability, the investigator team would like to exclude participants using illicit drugs. Occasional use of cannabis (once or twice per week) is not an exclusion factor. If the test is read as "indeterminate" it will be repeated at the bedside and an additional sample will be sent to the lab. Decision to enroll subject that day prior to results from lab being available will be decided on a case-by-case basis, i.e., when all previous drug testing had been negative and clinical suspicion is very low
  • Urinalysis: Clinically significant abnormalities
  • Clinically significant electrolyte abnormalities
  • Smoking >10 cigarettes/day
  • Alcohol: Men >14 drinks/week or >4 drinks/day, Women >7 drinks/week 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 (if euthyroid on thyroid hormone replacement - if such history free thyroxine (fT4) and Thyroid Stimulating Hormone (TSH) will be checked)
  • 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 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

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Meredith Hawkins, M.D., M.S. contact

718-430-2903

meredith.hawkins@einsteinmed.edu

United States1 site, 1 recruiting

  • Albert Einstein College of Medicine

    The Bronx, New York, 10461

    Meredith Hawkins, M.D., M.S.

    Recruiting

Other trials in United States

About this study

Type 2 diabetes (T2D) 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.

Read the detailed description

In this study, the investigators will study healthy participants through a procedure called a "pancreatic clamp" study. During the clamp procedure, glucose (a sugar) and insulin (a hormone produced in the pancreas that regulates the amount of glucose in the blood) are infused with an intravenous catheter, and blood samples are collected periodically throughout the procedure to measure blood sugar levels and the levels of several hormones that are found in the body and are related to glucose metabolism. Endogenous glucose production (a measure of the body's production of sugar) will be measured in patients given diazoxide (a medication that activates potassium channels in the brain that may affect glucose production in the liver through brain-liver signaling), compared with when a placebo is given. This study will also investigate whether lowering free fatty acid levels which may help improve the body's ability to regulate glucose levels.

Aim 1: non-diabetic participants will be studied after receiving diazoxide or placebo in a randomized, single-blinded fashion to determine whether extra-pancreatic KATP channels regulate hepatic glucose fluxes in non-diabetic humans.

For Aim 1, 15 healthy, non-diabetic individuals will be studied under the following experimental conditions, in random order and in double blinded fashion:

  1. normoglycemic 'pancreatic clamp' studies with administration of placebo
  2. normoglycemic 'pancreatic clamp' studies with administration of diazoxide

Aim 2: these non-diabetic participants will also be studied after receiving diazoxide or placebo in a randomized, single-blinded fashion after lowering their free fatty acid (FFA) levels to determine whether central regulation of glucose fluxes can be restored upon lowering FFA levels.

  1. normoglycemic (90 mg/dl) pancreatic clamp studies will be performed following nicotinic acid administration, and placebo
  2. normoglycemic (90 mg/dl) pancreatic clamp studies will be performed following nicotinic acid administration, and diazoxide
Being tested
Diazoxide, Nicotinic acid, Placebo
Keywords
Central KATP Channels, diabetes, diazoxide, endogenous glucose production
Medical subject headings
Diabetes Mellitus, Glucose Metabolism Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DiazoxideDrug

    Also called Proglycem

    Non-diabetic participants will receive diazoxide at a dose of 4-7 mg/kg (based upon weight) during the pancreatic clamp study.

  • Nicotinic acidDrug

    Also called Niacin

    Non-diabetic participants will receive nicotinic acid infusion based on weight (0.01 mg/kg/min) during the pancreatic clamp study.

  • PlaceboDrug

    Also called Control

    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.

Study groups in NCT03540758
Study groupRoleWhat they receive
Non-diabetic (Diazoxide)ExperimentalPancreatic clamp study will be done after giving Diazoxide (Proglycem) oral suspension to non-diabetic participants.
Receives: Drug: Diazoxide
Non-diabetic (Placebo)Placebo comparatorPancreatic clamp study will be done after giving a taste-matched placebo for Diazoxide (Proglycem) to non-diabetic participants.
Receives: Drug: Placebo
Non-diabetic (Diazoxide + Nicotinic Acid)ExperimentalPancreatic clamp study will be done after giving Diazoxide (Proglycem) oral suspension to non-diabetic participants after lowering free fatty acids with a nicotinic acid (Niacin) infusion
Receives: Drug: Diazoxide; Drug: Nicotinic acid
Non-diabetic (Nicotinic Acid + placebo for diazoxide)ExperimentalPancreatic clamp study will be done after lowering free fatty acids with a nicotinic acid (Niacin) infusion in non-diabetic participants, and after giving a taste-matched placebo for Diazoxide (Proglycem) toon-diabetic participants.
Receives: Drug: Nicotinic acid; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in Endogenous glucose production (EGP) rate

    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 (e.g., placebo, diazoxide, nicotinic acid, nicotinic acid/diazoxide), by monitoring changes in the level of a non-radioactive, naturally occurring form of glucose (sugar). Measurement of blood glucose concentrations will either be performed with a Precision Xceed Pro glucometer or an Analox glucose analyzer in the study room. Increased EGP is the major cause of fasting hyperglycemia. EGP will be determined by subtracting the rates of glucose infusion from the tracer-derived Rates of glucose appearance (Ra). Rates of change in EGP will be reported in concentration/time and summarized by study arm using basic descriptive statistics.

    Measured: 7 hour infusions, 4 days in total, separated at least 1 month apart, up to 1 year duration

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 May 2018
  2. Study start1 Aug 2018
  3. Primary completionApr 2027 (estimated)
  4. Study completionApr 2027 (estimated)

Resources

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
Masking
Single blind
Who is masked
Participant
Enrolment
100 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03540758
Sponsor's protocol ID
2018-9039
Other IDs
R01DK069861
Status last verified
Apr 2026
First submitted
17 May 2018
Last updated
28 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Data intended for broader use will be free of identifiers that would permit linkages to individual research participants. Data and associated documentation will be made available to users only if: 1. a commitment to using the data only for research purposes and not to identify any individual participant is provided; 2. a commitment to securing the data using appropriate computer technology; and 3. a commitment to destroying or returning the data after analyses are completed.

Publications

  • DeFronzo RA. Lilly lecture 1987. The triumvirate: beta-cell, muscle, liver. A collusion responsible for NIDDM. Diabetes. 1988 Jun;37(6):667-87. doi: 10.2337/diab.37.6.667. No abstract available.

    PubMed 3289989

  • Bogardus C, Lillioja S, Howard BV, Reaven G, Mott D. Relationships between insulin secretion, insulin action, and fasting plasma glucose concentration in nondiabetic and noninsulin-dependent diabetic subjects. J Clin Invest. 1984 Oct;74(4):1238-46. doi: 10.1172/JCI111533.

    PubMed 6384267

  • Campbell PJ, Mandarino LJ, Gerich JE. Quantification of the relative impairment in actions of insulin on hepatic glucose production and peripheral glucose uptake in non-insulin-dependent diabetes mellitus. Metabolism. 1988 Jan;37(1):15-21. doi: 10.1016/0026-0495(88)90023-6.

    PubMed 3275857

  • Reaven GM, Hollenbeck C, Jeng CY, Wu MS, Chen YD. Measurement of plasma glucose, free fatty acid, lactate, and insulin for 24 h in patients with NIDDM. Diabetes. 1988 Aug;37(8):1020-4. doi: 10.2337/diab.37.8.1020.

    PubMed 3292322

  • Lewis GF, Carpentier A, Adeli K, Giacca A. Disordered fat storage and mobilization in the pathogenesis of insulin resistance and type 2 diabetes. Endocr Rev. 2002 Apr;23(2):201-29. doi: 10.1210/edrv.23.2.0461.

    PubMed 11943743

  • Coppack SW, Jensen MD, Miles JM. In vivo regulation of lipolysis in humans. J Lipid Res. 1994 Feb;35(2):177-93.

    PubMed 8169522

  • Williamson JR, Kreisberg RA, Felts PW. Mechanism for the stimulation of gluconeogenesis by fatty acids in perfused rat liver. Proc Natl Acad Sci U S A. 1966 Jul;56(1):247-54. doi: 10.1073/pnas.56.1.247. No abstract available.

    PubMed 4381783

  • Massillon D, Barzilai N, Hawkins M, Prus-Wertheimer D, Rossetti L. Induction of hepatic glucose-6-phosphatase gene expression by lipid infusion. Diabetes. 1997 Jan;46(1):153-7. doi: 10.2337/diab.46.1.153.

    PubMed 8971097

  • van de Werve G, Lange A, Newgard C, Mechin MC, Li Y, Berteloot A. New lessons in the regulation of glucose metabolism taught by the glucose 6-phosphatase system. Eur J Biochem. 2000 Mar;267(6):1533-49. doi: 10.1046/j.1432-1327.2000.01160.x.

    PubMed 10712583

  • Jump DB, Clarke SD, Thelen A, Liimatta M. Coordinate regulation of glycolytic and lipogenic gene expression by polyunsaturated fatty acids. J Lipid Res. 1994 Jun;35(6):1076-84.

    PubMed 8077846

  • Lam TK, van de Werve G, Giacca A. Free fatty acids increase basal hepatic glucose production and induce hepatic insulin resistance at different sites. Am J Physiol Endocrinol Metab. 2003 Feb;284(2):E281-90. doi: 10.1152/ajpendo.00332.2002.

    PubMed 12531742

  • Oakes ND, Cooney GJ, Camilleri S, Chisholm DJ, Kraegen EW. Mechanisms of liver and muscle insulin resistance induced by chronic high-fat feeding. Diabetes. 1997 Nov;46(11):1768-74. doi: 10.2337/diab.46.11.1768.

    PubMed 9356024

  • Gustafson LA, Neeft M, Reijngoud DJ, Kuipers F, Sauerwein HP, Romijn JA, Herling AW, Burger HJ, Meijer AJ. Fatty acid and amino acid modulation of glucose cycling in isolated rat hepatocytes. Biochem J. 2001 Sep 15;358(Pt 3):665-71. doi: 10.1042/0264-6021:3580665.

    PubMed 11535127

  • Hawkins M, Gabriely I, Wozniak R, Reddy K, Rossetti L, Shamoon H. Glycemic control determines hepatic and peripheral glucose effectiveness in type 2 diabetic subjects. Diabetes. 2002 Jul;51(7):2179-89. doi: 10.2337/diabetes.51.7.2179.

    PubMed 12086948

  • Hawkins M, Tonelli J, Kishore P, Stein D, Ragucci E, Gitig A, Reddy K. Contribution of elevated free fatty acid levels to the lack of glucose effectiveness in type 2 diabetes. Diabetes. 2003 Nov;52(11):2748-58. doi: 10.2337/diabetes.52.11.2748.

    PubMed 14578293

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Diazoxide and Nicotinic acid in people with Diabetes Mellitus and Glucose Metabolism Disorders, run by Albert Einstein College of Medicine 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 14 inclusion and 25 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: looking for participants now, as of the sponsor's last update on 28 Apr 2026. 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?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Meredith Hawkins, M.D., M.S. (718-430-2903, meredith.hawkins@einsteinmed.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Endogenous glucose production (EGP) rate (time frame: 7 hour infusions, 4 days in total, separated at least 1 month apart, up to 1 year duration). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03540758, which also lists 42 linked publications.

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 28 Apr 2026.

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