Autonomic Blockade and Endogenous Glucose Production

NCT03028571 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: 150466
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Insulin Resistance

Outcome Measures

Primary Outcomes (1)

• Endogenous Glucose Production

  Amount of label glucose appearance

  Duration of the study (4 hours)

Study Arms (2)

Intact Day

PLACEBO COMPARATOR

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

Other: Saline

Blocked Day

EXPERIMENTAL

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.

Drug: Trimethaphan

Interventions

Trimethaphan DRUG

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.

Blocked Day

Saline OTHER

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

Intact Day

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Insulin Resistance

Interventions

Trimethaphan; Sodium Chloride

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine and Pharmacology

Model Details: 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

Study Record Dates

• First Submitted: January 18, 2017
• First Posted: January 23, 2017
• Study Start: April 17, 2017
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2024
• Last Updated: June 8, 2021

Record last verified: 2021-06

Locations

US (1)