The Autonomic Nervous System and the Metabolic Syndrome

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.

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Key information

Conditions

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

Age range

18 year–60 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

About this study

The purpose of this study is to look at the role of the autonomic nervous system, an involuntary nervous system that controls your blood pressure, in insulin resistance and the metabolic syndrome. Insulin is a substance that helps your body use the sugar in the food that you eat. Some people's tissues stop reacting in a normal way to insulin, a condition known as insulin resistance. A person with insulin resistance can have other health problems, such as obesity, high cholesterol, and high blood pressure. These problems together are called the metabolic syndrome. We think that the autonomic or involuntary nervous system controls the way your body responds to insulin. This system is changed in obese people, and we think that it may cause the insulin resistance. We plan to study this with two drugs -trimethaphan and L-NMMA. Neither of these drugs are approved by the Food and Drug Administration (FDA), and they will be used for research purposes only.

Fifty people will take part in this study.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

For lean subjects:
21 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:
21 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.

Exclusion criteria

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.

Treatment and study plan

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

Other names: Trimethaphan

Intact

Drug

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

Other names: Saline

Primary outcomes

Insulin Resistance

Time frame: Last 30 minutes of a two hour insulin clamp

Glucose infusion rate in mg/kg/min

Sponsors and collaborators

Lead sponsor

Vanderbilt University

Other

Registry information

Important dates

Study start: 2008
Primary completion: 2015
Study completion: 2015
First posted: Dec 27, 2007
Registry last updated: Aug 5, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

Completed