Purpose

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.

Conditions

Eligibility

Eligible Ages
Between 21 Years and 70 Years
Eligible Genders
All
Accepts Healthy Volunteers
Yes

Inclusion Criteria

For healthy participants:

- Age: 21-70 y.o.

- BMI under 30

- 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 for T2D and >30 for non-diabetic (ND)
  • 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

Study Design

Phase
Phase 2
Study Type
Interventional
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.
Primary Purpose
Basic Science
Masking
Single (Participant)
Masking Description
The subject will be blinded as to which study drug he/she is receiving first (Drug or Placebo).

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Non-diabetic (Diazoxide)
Pancreatic clamp study will be done after giving Diazoxide (Proglycem) oral suspension to non-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 names:
    • 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.
  • Drug: Placebo
    Non-diabetic participants will receive placebo and undergo the pancreatic clamp study. T2D participants will be admitted the evening before the study day to normalize blood sugar levels to that of a healthy person. They will then receive placebo the next morning and undergo 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 names:
    • 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 be admitted the evening before the study day to normalize blood sugar levels to that of a healthy person. They will then receive placebo the next morning and undergo 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 names:
    • 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 names:
    • Niacin
Experimental
T2D (Nicotinic Acid Only)
Pancreatic clamp study will be done after lowering free fatty acids with a nicotinic acid (Niacin) infusion in type 2 diabetic participants.
  • 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 names:
    • Niacin

Recruiting Locations

Albert Einstein College of Medicine
Bronx, New York 10461

More Details

NCT ID
NCT03540758
Status
Recruiting
Sponsor
Albert Einstein College of Medicine

Study Contact

Tusli Patel
718-430-2903
tulsi.patel@einsteinmed.org

Detailed Description

In this study, the investigators will study healthy participants and participants with type 2 diabetes 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 the body's ability to regulate glucose levels.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.