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Regulation of Endogenous Glucose Production by Central KATP Channels

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ClinicalTrials.gov Identifier: NCT03540758
Recruitment Status : Recruiting
First Posted : May 30, 2018
Last Update Posted : September 17, 2018
Sponsor:
Collaborators:
National Institutes of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Meredith Hawkins, Albert Einstein College of Medicine

Brief Summary:
The goal of this study is to understand how activating control centers of the brain with diazoxide can affect how much glucose (sugar) is produced by the liver. This is particularly important for people with diabetes who have very high production of glucose, since this could be at least in part due to impaired regulation of the liver by the brain.

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

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, in which hormones such as insulin and glucose are infused through an IV to carefully control blood sugar levels.

All participants will be screened prior to study enrollment. Eligible participants will have 2 study visits (one study with diazoxide +/- nicotinic acid and one study with placebo) that will include overnight admissions for participants with Type 2 diabetes. Healthy participants will not have to stay for an overnight admission.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
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 : November 2020
Estimated Study Completion Date : November 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Healthy (Diazoxide)

Diazoxide (Proglycem), oral suspension (4-6 mg/kg)

Healthy participants in this arm will receive diazoxide.

Drug: Diazoxide

Healthy participants will not require an overnight admission. They will receive diazoxide at a dose of 4-6 mg/kg (based upon weight) 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 diazoxide at a dose of 4-6mg/kg (based upon weight) the next morning and undergo the pancreatic clamp study.

Other Name: Proglycem

Placebo Comparator: Healthy (Placebo)

Taste-matched placebo.

Healthy participants in this arm will receive placebo.

Drug: Placebo

Healthy participants will not require an overnight admission. They 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)

Diazoxide (Proglycem), oral suspension (4-6 mg/kg)

Type 2 Diabetic (T2D) participants in this arm will receive diazoxide.

Drug: Diazoxide

Healthy participants will not require an overnight admission. They will receive diazoxide at a dose of 4-6 mg/kg (based upon weight) 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 diazoxide at a dose of 4-6mg/kg (based upon weight) the next morning and undergo the pancreatic clamp study.

Other Name: Proglycem

Placebo Comparator: T2D (Placebo)

Taste-matched placebo.

Type 2 Diabetic (T2D) participants in this arm will receive placebo.

Drug: Placebo

Healthy participants will not require an overnight admission. They 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)

Diazoxide (Proglycem), oral suspension (4-6 mg/kg) Nicotinic Acid (Niacin) , infusion

Type 2 Diabetic (T2D) participants in this arm will receive Diazoxide and Nicotinic Acid.

Drug: Diazoxide

Healthy participants will not require an overnight admission. They will receive diazoxide at a dose of 4-6 mg/kg (based upon weight) 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 diazoxide at a dose of 4-6mg/kg (based upon weight) the next morning and undergo the pancreatic clamp study.

Other Name: Proglycem

Drug: Nicotinic acid
T2D participants will be admitted the evening before the study day to normalize blood sugar levels to that of a healthy person. They will additionally receive nicotinic acid infusion to lower free fatty acid levels. They will then receive diazoxide at a dose of 4-6mg/kg (based upon weight) the next morning and undergo the pancreatic clamp study.
Other Name: Niacin

Experimental: T2D (Nicotinic Acid Only)

Nicotinic Acid (Niacin) , infusion

Type 2 Diabetic (T2D) participants in this arm will receive Nicotinic Acid.

Drug: Nicotinic acid
T2D participants will be admitted the evening before the study day to normalize blood sugar levels to that of a healthy person. They will additionally receive nicotinic acid infusion to lower free fatty acid levels. They will then receive diazoxide at a dose of 4-6mg/kg (based upon weight) the next morning and undergo the pancreatic clamp study.
Other Name: Niacin




Primary Outcome Measures :
  1. Endogenous glucose production (EGP) [ Time Frame: 7-7.5 hours ]
    Rates of EGP will be measured during pancreatic clamp studies, with suppression of pancreatic hormones by somatostatin infusion and basal hormone replacement



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Ages Eligible for Study:   21 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

For healthy participants:

  • Age: 21-65 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: 21-65 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 symptomatic neuropathy (including cardiovascular and gastrointestinal autonomic dysfunction).

Exclusion Criteria:

  • Age: Under 21 or over 65 y.o.
  • BMI: >35 for T2D and >30 for ND
  • Hypertension
  • 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
  • Anemia
  • Leukocytosis or leukopenia
  • Thrombocytopenia or thrombocytosis
  • Coagulopathy
  • Positive urine drug screen
  • Urinalysis: Clinically significant abnormalities
  • Clinically significant electrolyte abnormalities
  • Smoking >7 cig/day
  • Alcohol: Men >14 drinks/wk or > 4drinks/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
  • Any condition which in the opinion of the PI makes the subject ill suited for participation in the study

Information from the National Library of Medicine

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


Contacts
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Contact: Matthew Zhao, B.S. 718-430-2903 matthew.zhao@einstein.yu.edu

Locations
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United States, New York
Albert Einstein College of Medicine Recruiting
Bronx, New York, United States, 10461
Contact: Matthew Zhao, B.S.    718-430-2903    matthew.zhao@einstein.yu.edu   
Principal Investigator: Meredith Hawkins, M.D., M.S.         
Sponsors and Collaborators
Albert Einstein College of Medicine
National Institutes of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
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Principal Investigator: Meredith Hawkins, M.D., M.S. Albert Einstein College of Medicine

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Responsible Party: Meredith Hawkins, Principal Investigator, Albert Einstein College of Medicine
ClinicalTrials.gov Identifier: NCT03540758     History of Changes
Other Study ID Numbers: 2018-9039
R01DK069861 ( U.S. NIH Grant/Contract )
First Posted: May 30, 2018    Key Record Dates
Last Update Posted: September 17, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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

Keywords provided by Meredith Hawkins, Albert Einstein College of Medicine:
type 2 diabetes
diabetes
insulin resistance
diazoxide

Additional relevant MeSH terms:
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Metabolic Diseases
Glucose Metabolism Disorders
Endocrine System Diseases
Diabetes Mellitus
Diabetes Mellitus, Type 2
Hyperglycemia
Niacin
Diazoxide
Nicotinic Acids
Niacinamide
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