The Autonomic Nervous System and the Metabolic Syndrome

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Italo Biaggioni, Vanderbilt University
ClinicalTrials.gov Identifier:
NCT00580957
First received: December 20, 2007
Last updated: February 12, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention
Obesity
Drug: Trimethaphan L-NMMA Insulin clamp
Drug: Saline, Insulin clamp

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Official Title: The Autonomic Nervous System and the Metabolic Syndrome

Resource links provided by NLM:


Further study details as provided by Vanderbilt University:

Primary Outcome Measures:
  • Insulin resistance [ Time Frame: Duration of the intervention ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Muscle sympathetic nerve activity [ Time Frame: Duration of the intervention ] [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: August 2008
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Active treatment arm. Transient autonomic blockade with Trimethaphan and blood pressure restoration with L-NMMA will be used during insulin clamp
Drug: Trimethaphan L-NMMA Insulin clamp
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
Placebo Comparator: 2
Saline will be used instead of trimethaphan during insulin clamp
Drug: Saline, Insulin clamp
Saline IV infusion to simulate trimethaphan infusion in active arm Insulin clamp will be done to determine insulin resistance

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.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • For lean subjects:
  • 20 subjects (10 males and 10 females) 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:
  • 20 subjects (10 males and 10 females) 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00580957

Locations
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Vanderbilt University
Investigators
Principal Investigator: Italo Biaggioni, M.D. Vanderbilt University
  More Information

No publications provided

Responsible Party: Italo Biaggioni, Professor of Medicine and Pharmacology, Vanderbilt University
ClinicalTrials.gov Identifier: NCT00580957     History of Changes
Other Study ID Numbers: 060085, CRC-1522
Study First Received: December 20, 2007
Last Updated: February 12, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Vanderbilt University:
Obesity
Hypertension
Autonomic Nervous System

Additional relevant MeSH terms:
Obesity
Metabolic Syndrome X
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Insulin, Globin Zinc
Insulin
Trimethaphan
Trimethaphan camsylate
Omega-N-Methylarginine
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Adjuvants, Anesthesia
Central Nervous System Agents
Therapeutic Uses
Antihypertensive Agents
Cardiovascular Agents
Ganglionic Blockers
Autonomic Agents
Peripheral Nervous System Agents
Nicotinic Antagonists
Cholinergic Antagonists
Cholinergic Agents

ClinicalTrials.gov processed this record on August 18, 2014