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Central Mechanisms That Regulate Glucose Metabolism in Humans

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ClinicalTrials.gov Identifier: NCT01028846
Recruitment Status : Recruiting
First Posted : December 9, 2009
Last Update Posted : January 17, 2018
Sponsor:
Collaborators:
Information provided by (Responsible Party):

Study Description
Brief Summary:

Increased endogenous glucose production (EGP) is the major cause of postabsorptive hyperglycemia in type 2 diabetes mellitus (T2DM). While EGP is inhibited by both glucose and insulin in non-diabetic animals and humans, T2DM is associated with increased EGP despite elevated plasma glucose and insulin concentrations. In fact, we and others have reported direct inhibitory effects of hyperglycemia itself on EGP in nondiabetic subjects, independent of other hormonal or metabolic signals, which are markedly blunted in subjects with T2DM.

The medial hypothalamus mediates hormonal signals which affect glucose metabolism. ATP-sensitive potassium (KATP) channels are expressed in the hypothalamus and can be activated by insulin. Activation of these channels appears to be an important common mechanism whereby both systemic glucose and insulin suppress EGP, and may account for almost 50% of EGP suppression by both agents. Diazoxide has been shown to inhibit EGP in rodents via the activation of these KATP channels in the hypothalamus, while the KATP channel inhibitor glyburide blocks these effects. There is evidence to suggest that central activation of KATP channels is still able to suppress EGP in animal models that are otherwise resistant to the effects of systemic glucose and insulin.


Condition or disease Intervention/treatment Phase
Type 2 Diabetes Drug: Diazoxide Drug: Glyburide Device: Vagal Nerve Stimulator Phase 2

Detailed Description:
The current proposal will address the potential impact of diazoxide on inhibiting EGP, and ultimately to investigate its use as a potential treatment for diabetes mellitus. Additionally, to determine the importance of central signaling to the effects of hyperglycemia and hyperinsulinemia on EGP in humans, we will administer glyburide prior to raising glucose or insulin levels under controlled clamp conditions.

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: Central Mechanisms That Regulate Glucose Metabolism in Humans
Study Start Date : May 2011
Estimated Primary Completion Date : September 2022
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Glyburide
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Active Comparator: Diazoxide
administered orally
Drug: Diazoxide
4mg-6mg/kg orally once before study
Other Name: Proglycem
Active Comparator: Glyburide
administered orally
Drug: Glyburide
Administered orally at beginning of study
Active Comparator: Vagal Nerve Stimulator
VNS device
Device: Vagal Nerve Stimulator
Device approved for the purpose of decreasing seizure frequency in patients with poorly-controlled epilepsy


Outcome Measures

Primary Outcome Measures :
  1. Endogenous Glucose Production (EGP) [ Time Frame: 4 hours ]
    Rates of EGP will be measured during pancreatic clamp studies, with suppression of pancreatic hormones by somatostatin infusion and basal hormone replacement


Secondary Outcome Measures :
  1. Glucose Uptake [ Time Frame: 4 hours ]
    Glucose Uptake will be measured during pancreatic clamp studies, with suppression of pancreatic hormones by somatostatin infusion and basal hormone replacement


Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

HEALTHY

  • BP < 130/90 (+-2 meds)
  • BMI 23-27
  • No family history of diabetes
  • Noth other medical problems with exception: HTN (on < or = 2 meds), hypercholesterolemia, and stable retinopathy
  • Non-smoker

DIABETIC

  • BMI 27-32
  • A1C >8

Exclusion Criteria:

  • BP>130/90 (+- medications)
  • BMI > 27
  • Abnormal EKG
  • History of CAD or exertional chest pain
  • First degree relative with early CAD or MI
  • Medications for medical or psychiatric conditions including: dofetilide, fosphenytoin/phenytoin trichlormethiazide (any thiazide), chlorpromazine and warfarin
  • < 4 week history of participation in another drug trial
Contacts and Locations

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): NCT01028846


Contacts
Contact: Tiffany S Cheng, B.S. 718-430-2903 tiffany.cheng@einstein.yu.edu

Locations
United States, New York
Albert Einstein College of Medicine of Yeshiva University Recruiting
Bronx, New York, United States, 10461
Principal Investigator: Meredith Hawkins, MD         
Sponsors and Collaborators
Albert Einstein College of Medicine, Inc.
National Institutes of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
Principal Investigator: Meredith Hawkins, M.D., M.S. Albert Einstein College of Medicine, Inc.
More Information

Responsible Party: Meredith Hawkins, M.D., M.S., Professor, Albert Einstein College of Medicine, Inc.
ClinicalTrials.gov Identifier: NCT01028846     History of Changes
Other Study ID Numbers: 2006-414
R01DK069861 ( U.S. NIH Grant/Contract )
First Posted: December 9, 2009    Key Record Dates
Last Update Posted: January 17, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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, Inc.:
Type 2 Diabetes

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Glyburide
Diazoxide
Hypoglycemic Agents
Physiological Effects of Drugs
Antihypertensive Agents
Vasodilator Agents