The Autonomic Nervous System and the Metabolic Syndrome

NCT ID: NCT00580957

Last Updated: 2016-08-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 56 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-08-31
• Study Completion Date: 2015-05-31

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.

Detailed 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.

Conditions

Obesity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Blinding Strategy: SINGLE

Study Groups

Blocked

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

Group Type: EXPERIMENTAL

Blocked

Intervention Type: 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

Intact

Saline will be used instead of trimethaphan during insulin clamp

Group Type: PLACEBO_COMPARATOR

Intact

Intervention Type: DRUG

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

Interventions

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

Intervention Type: DRUG

Intact

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

Intervention Type: DRUG

Other Intervention Names

Trimethaphan; Saline

Eligibility Criteria

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):

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Vanderbilt University

OTHER

Sponsor Role: lead

Responsible Party

Italo Biaggioni

Professor of Medicine and Pharmacology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Italo Biaggioni, M.D.

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University

Locations

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Countries

United States

Other Identifiers

CRC-1522

Identifier Type: OTHER

Identifier Source: secondary_id

060085

Identifier Type: -

Identifier Source: org_study_id