Back to results

Autonomic Blockade and Endogenous Glucose Production

Primary Purpose

Insulin Resistance

Status

Withdrawn

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Trimethaphan

Saline

About this trial

This is an interventional basic science trial for Insulin Resistance

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Males and females of all races between 18 and 60 years of age
Hypertension defined by two or more properly measured seated blood pressure readings >130/85 mmHg or currently on antihypertensive medication. This will allow us to include subjects with "pre-hypertension."
Obesity will be defined as having a body mass index (BMI) ≥ 30 kg/m2.
Insulin resistance will be defined as a HOMA2 IR index ≥1.6
Able and willing to provide informed consent

Exclusion Criteria:

Pregnancy or breast feeding
Current smokers or history of heavy smoking (>2 packs/day)
History of alcohol or drug abuse
Previous allergic reaction to study medications
Evidence of type I or type II diabetes (i.e. fasting glucose >126 mg/dl, use of anti-diabetic medications)
Cardiovascular disease other than hypertension such as myocardial infarction within 6 months prior to enrollment, presence of angina pectoris, significant arrhythmia, congestive heart failure (LV hypertrophy acceptable), deep vein thrombosis, pulmonary embolism, second or third degree heart block, mitral valve stenosis, aortic stenosis, or hypertrophic cardiomyopathy
History of serious cerebrovascular disease such as cerebral hemorrhage, stroke, or transient ischemic attack
History or presence of immunological or hematological disorders
Impaired renal function
Anemia
Treatment with phosphodiesterase 5 inhibitors
Treatment with anticoagulants
Treatment with chronic systemic glucocorticoid therapy (more than 7 consecutive days in 1 month)
Treatment with any investigational drug in the 1 month preceding the study
Inability to give, or withdraw, informed consent
Other factors which in the investigator's opinion would prevent the subject from completing the protocol (i.e., clinically significant abnormalities on clinical, mental examination or laboratory testing or inability to comply with protocol, inability to find IV access)

Sites / Locations

Vanderbilt University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Intact Day

Blocked Day

Arm Description

The rates of endogenous glucose appearance (Ra) and peripheral glucose uptake (Rd) will be measured during a regular insulin clamp with concomitant infusion of saline at 48 ml/hr IV

The rates of endogenous glucose appearance (Ra) and peripheral glucose uptake (Rd) will be measured during a regular insulin clamp with concomitant infusion of trimethaphan (4mg/min) IV.

Outcomes

Primary Outcome Measures

Endogenous Glucose Production

Amount of label glucose appearance

Secondary Outcome Measures

Full Information

NCT ID

NCT03028571

First Posted

January 18, 2017

Last Updated

June 3, 2021

Sponsor

Vanderbilt University Medical Center

1. Study Identification

Unique Protocol Identification Number

NCT03028571

Brief Title

Autonomic Blockade and Endogenous Glucose Production

Official Title

Acute Sympathetic Blockade and Endogenous Glucose Production

Study Type

Interventional

2. Study Status

Record Verification Date

June 2021

Overall Recruitment Status

Withdrawn

Why Stopped

The investigators decided not to perform the study. No participants have been enrolled.

Study Start Date

April 17, 2017 (Actual)

Primary Completion Date

December 31, 2022 (Anticipated)

Study Completion Date

December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Vanderbilt University Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

The investigators will test the null hypothesis that there will be no changes in the insulin-mediated suppression of endogenous glucose production (EGP) in response to autonomic blockade. To test this hypothesis, the investigators propose to determine the role of the autonomic nervous system in hepatic insulin resistance.

Detailed Description

In this study, the investigators will test the null hypothesis that there will be no changes in the insulin-mediated suppression of endogenous glucose production (EGP) in response to autonomic blockade. The investigators will measure EGP at baseline (EGPBsl) and during the last 30 minutes of a hyperinsulinemic euglycemic clamp (EGPClamp) on two different occasions (intact and Blocked study days). A double blinded randomize cross-over design will be used. Subjects will be randomized to either the intact or blocked days and a month later will be crossed-over to the other arm. The investigator performing the analysis will also be blinded to the treatments received. At baseline in both study days it is expected to see any differences since the same subject will serve as his own control. During the clamp, insulin suppresses EGP. In obese insulin resistant subjects this suppression should be blunted. If the hypothesis is correct, it is expected an improvement in the suppression by insulin of EGP during autonomic blockade only. For this study, the primary endpoint therefore, will be the EGP during the clamp between the intact and blocked days. H0= {(EGPClamp)Blocked - (EGPClamp)Intact}=0]

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Insulin Resistance

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1

Interventional Study Model

Crossover Assignment

Model Description

Subjects will be studied twice, randomly assigned to star on the intact day (saline) or the blocked day (trimethaphan) and after 1 month cross to the other arm

Masking

Participant

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Intact Day

Arm Type

Placebo Comparator

Arm Description

The rates of endogenous glucose appearance (Ra) and peripheral glucose uptake (Rd) will be measured during a regular insulin clamp with concomitant infusion of saline at 48 ml/hr IV

Arm Title

Blocked Day

Arm Type

Experimental

Arm Description

The rates of endogenous glucose appearance (Ra) and peripheral glucose uptake (Rd) will be measured during a regular insulin clamp with concomitant infusion of trimethaphan (4mg/min) IV.

Intervention Type

Drug

Intervention Name(s)

Trimethaphan

Intervention Description

Trimethaphan 4 mg/min IV will be given as a pharmacological tool to study the role of the autonomic nervous system on the regulation of endogenous glucose production by the liver.

Intervention Type

Other

Intervention Name(s)

Saline

Intervention Description

IV saline at a rate of 48 mL/hr, will be given during the insulin clamp to resemble the volume infused in the intact day

Primary Outcome Measure Information:

Title

Endogenous Glucose Production

Description

Amount of label glucose appearance

Time Frame

Duration of the study (4 hours)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Males and females of all races between 18 and 60 years of age Hypertension defined by two or more properly measured seated blood pressure readings >130/85 mmHg or currently on antihypertensive medication. This will allow us to include subjects with "pre-hypertension." Obesity will be defined as having a body mass index (BMI) ≥ 30 kg/m2. Insulin resistance will be defined as a HOMA2 IR index ≥1.6 Able and willing to provide informed consent Exclusion Criteria: Pregnancy or breast feeding Current smokers or history of heavy smoking (>2 packs/day) History of alcohol or drug abuse Previous allergic reaction to study medications Evidence of type I or type II diabetes (i.e. fasting glucose >126 mg/dl, use of anti-diabetic medications) Cardiovascular disease other than hypertension such as myocardial infarction within 6 months prior to enrollment, presence of angina pectoris, significant arrhythmia, congestive heart failure (LV hypertrophy acceptable), deep vein thrombosis, pulmonary embolism, second or third degree heart block, mitral valve stenosis, aortic stenosis, or hypertrophic cardiomyopathy History of serious cerebrovascular disease such as cerebral hemorrhage, stroke, or transient ischemic attack History or presence of immunological or hematological disorders Impaired renal function Anemia Treatment with phosphodiesterase 5 inhibitors Treatment with anticoagulants Treatment with chronic systemic glucocorticoid therapy (more than 7 consecutive days in 1 month) Treatment with any investigational drug in the 1 month preceding the study Inability to give, or withdraw, informed consent Other factors which in the investigator's opinion would prevent the subject from completing the protocol (i.e., clinically significant abnormalities on clinical, mental examination or laboratory testing or inability to comply with protocol, inability to find IV access)

Facility Information:

Facility Name

Vanderbilt University Medical Center

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37232

Country

United States

12. IPD Sharing Statement

Learn more about this trial

Autonomic Blockade and Endogenous Glucose Production

We'll reach out to this number within 24 hrs