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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, 2019
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

Tracking Information
First Submitted Date  ICMJE May 17, 2018
First Posted Date  ICMJE May 30, 2018
Last Update Posted Date September 17, 2019
Actual Study Start Date  ICMJE August 1, 2018
Estimated Primary Completion Date November 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 13, 2019)
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).
Original Primary Outcome Measures  ICMJE
 (submitted: May 17, 2018)
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
Change History Complete list of historical versions of study NCT03540758 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Regulation of Endogenous Glucose Production by Central KATP Channels
Official Title  ICMJE Regulation of Endogenous Glucose Production by Central KATP Channels
Brief Summary

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.

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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE 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
Condition  ICMJE
  • Type 2 Diabetes Mellitus
  • Glucose Metabolism Disorders
  • Glucose, High Blood
Intervention  ICMJE
  • 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
  • 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.

Study Arms  ICMJE
  • Experimental: Non-diabetic (Diazoxide)
    Pancreatic clamp study will be done after giving Diazoxide (Proglycem) oral suspension to non-diabetic participants.
    Intervention: Drug: Diazoxide
  • Placebo Comparator: Non-diabetic (Placebo)
    Pancreatic clamp study will be done after giving a taste-matched placebo for Diazoxide (Proglycem) to non-diabetic participants.
    Intervention: Drug: Placebo
  • Experimental: T2D (Diazoxide)
    Pancreatic clamp study will be done after giving Diazoxide (Proglycem) oral suspension to type 2 diabetic participants.
    Intervention: Drug: Diazoxide
  • Placebo Comparator: T2D (Placebo)
    Pancreatic clamp study will be done after giving a taste-matched placebo for Diazoxide (Proglycem) to type 2 diabetic participants.
    Intervention: Drug: Placebo
  • 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.
    Interventions:
    • Drug: Diazoxide
    • Drug: Nicotinic acid
  • 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.
    Intervention: Drug: Nicotinic acid
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 17, 2018)
45
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 2021
Estimated Primary Completion Date November 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Joy Moy 718-430-2903 joy.moy@einstein.yu.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03540758
Other Study ID Numbers  ICMJE 2018-9039
R01DK069861 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Meredith Hawkins, Albert Einstein College of Medicine
Study Sponsor  ICMJE Albert Einstein College of Medicine
Collaborators  ICMJE
  • National Institutes of Health (NIH)
  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators  ICMJE
Principal Investigator: Meredith Hawkins, M.D., M.S. Albert Einstein College of Medicine
PRS Account Albert Einstein College of Medicine
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP