The Autonomic Nervous System and the Metabolic Syndrome

NCT00580957 | Completed Results

• 2 other identifiers: 060085CRC-1522
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

The overall goal of this proposal is to determine the role of the autonomic nervous system in the insulin resistant state associated with obesity and the metabolic syndrome. Obesity results from an accumulation of excessive fat deposit due to increase caloric intake or decrease energy expenditure, this condition is usually associated with diseases such as hypertension or diabetes, a cluster known as the metabolic syndrome. The first step in the development of the metabolic syndrome is a resistance to the action of insulin. The mechanism underlying insulin resistance in obesity is still unknown, however some investigators have proposed that the autonomic nervous system, particularly the increase sympathetic activation in obesity may play an important role. We have extensive experience studying the role of the autonomic nervous system in the cardiovascular alterations associated with obesity by producing complete autonomic withdrawal with a drug named trimethaphan. We propose to use the same approach to study the role of the autonomic nervous system in the development of insulin resistance in obesity.

Conditions

Obesity

Keywords

Obesity; Hypertension; Autonomic Nervous System

Outcome Measures

Primary Outcomes (1)

• Insulin Resistance

  Glucose infusion rate in mg/kg/min

  Last 30 minutes of a two hour insulin clamp

Study Arms (2)

Blocked

EXPERIMENTAL

Active treatment arm. Transient autonomic blockade with Trimethaphan and blood pressure restoration with L-NMMA will be used during insulin clamp

Drug: Blocked

Intact

PLACEBO COMPARATOR

Saline will be used instead of trimethaphan during insulin clamp

Drug: Intact

Interventions

Blocked DRUG

Trimethaphan 4 mg/min IV will be infused for the duration of the study. L-NMMA 125-500 mcg/k/min IV will be titrated to restore blood pressure to pre-trimethaphan levels Insulin clamp will be used to determine insulin resistance

Also known as: Trimethaphan

Blocked

Intact DRUG

Saline IV infusion to simulate trimethaphan infusion in active arm Insulin clamp will be done to determine insulin resistance

Also known as: Saline

Intact

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• For lean subjects:
• subjects aged 18-60 yr.
• All potential volunteers will have routine blood test to screen for hepatic, renal, and hematological abnormalities.
• Body mass index \< 25Kg/m\^2 .
• Female volunteers of childbearing potential will undergo HCG pregnancy test at screening and again on the study day.
• For Obese subjects with metabolic syndrome:
• subjects aged 18-60 yr.
• All potential volunteers will have routine blood test to screen for hepatic, renal, and hematological abnormalities.
• Body mass index \> 30Kg/m\^2.
• Participants will be enrolled if they met at least three of the following criteria for metabolic syndrome (Expert panel, Jama 2001):
• Waist circumference \>102 cm in men and \>88 cm in women
• High fasting blood sugar (\>110 mg%)
• Triglyceride levels \>150 mg%
• Low HDL cholesterol (\<40 mg% for men; \<50 mg% for women)
• High blood pressure (systolic=130 and diastolic = 85 mmHg) • Female volunteers of childbearing potential will undergo serum HCG pregnancy test at screening and urine HCG pregnancy test again on the study day.

You may not qualify if:

• Pregnant females
• Subjects unable to give voluntary informed consent
• Subjects on anticoagulant drugs or anemic (anemia defined as Hcto less than 35%)
• Subjects with a recent medical illness documented by physicians's visit or detected during the screening visit.
• Subjects with a history of coronary heart disease.
• Subjects with known kidney or liver disease.
• Subjects with recent weight loss or consuming low carbohydrate diet.

Sponsors & Collaborators

• Vanderbilt University: lead

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Obesity; Hypertension

Interventions

Dental Occlusion; Trimethaphan; Sodium Chloride

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Dentistry; Dental Physiological Phenomena; Digestive System and Oral Physiological Phenomena; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: Italo Biaggioni, M.D. Professor of Medicine
• Organization: Vanderbilt University

italo.biaggioni@vanderbilt.edu

(615) 936-3420

Study Officials

• Italo Biaggioni, M.D.

  Vanderbilt University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine and Pharmacology

Study Record Dates

• First Submitted: December 20, 2007
• First Posted: December 27, 2007
• Study Start: August 1, 2008
• Primary Completion: May 1, 2015
• Study Completion: May 1, 2015
• Last Updated: August 5, 2016
• Results First Posted: June 17, 2015

Record last verified: 2016-07

Locations

US (1)