The Autonomic Nervous System and the Metabolic Syndrome

Obesity Clinical Trial

Official title:

The Autonomic Nervous System and the Metabolic Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00580957
• Other study ID #: 060085
• Secondary ID: CRC-1522
• Status: Completed
• Phase: N/A
• First received: December 20, 2007
• Last updated: May 29, 2015
• Start date: August 2008
• Est. completion date: May 2015

Study information

• Verified date: May 2015
• Source: Vanderbilt University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: May 2015
• Est. primary completion date: May 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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/m2 .

• 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/m2.

• Participants will be enrolled if they met at least three of the following criteria for metabolic syndrome (Expert panel, Jama 2001):

1. Waist circumference >102 cm in men and >88 cm in women

2. High fasting blood sugar (>110 mg%)

3. Triglyceride levels >150 mg%

4. Low HDL cholesterol (<40 mg% for men; <50 mg% for women)

5. 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.

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject)

Related Conditions & MeSH terms

• Metabolic Syndrome X
• Obesity

Intervention

Drug:
• Blocked
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
• Intact
Saline IV infusion to simulate trimethaphan infusion in active arm Insulin clamp will be done to determine insulin resistance

Locations

Country	Name	City	State
United States	Vanderbilt University Medical Center	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Vanderbilt University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Insulin Resistance	Glucose infusion rate in mg/kg/min	Duration of the intervention	No