The Autonomic Nervous System and Obesity

This study is currently recruiting participants.
Verified June 2013 by Vanderbilt University
Sponsor:
Information provided by (Responsible Party):
Italo Biaggioni, Vanderbilt University
ClinicalTrials.gov Identifier:
NCT00179023
First received: September 13, 2005
Last updated: June 20, 2013
Last verified: June 2013
  Purpose

In its simplest terms, obesity is the results of a positive balance between food intake and energy expenditure (EE). I.e., we take in more energy, in the form of food, than we expend, e.g., by exercise. In our sedentary society, resting EE accounts for most of total energy expenditure. The sympathetic nervous system (SNS, the one that produces adrenaline) is thought to contribute to resting EE. This conclusion is based on experiments where resting EE is decreased by beta-blockers, high blood pressure medicines that block only one aspect of the sympathetic nervous system. The investigators propose to use a different approach, by using a medication called trimethaphan that produces transient withdrawal of the autonomic nervous system. The investigators will then compare the measured resting EE before and after SNS withdraw and quantify the degree of contribution to the resting EE by the SNS and delineate differences between healthy normal, healthy obese, and patients with autonomic dysfunctions.


Condition Intervention Phase
OBESITY
HYPERTENSION
PURE AUTONOMIC FAILURE
SHY-DRAGER SYNDROME
Drug: Trimethaphan
Drug: Pseudoephedrine
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: The Autonomic Nervous System and Obesity

Resource links provided by NLM:


Further study details as provided by Vanderbilt University:

Primary Outcome Measures:
  • Change in supine systolic blood pressure after achieving complete ganglionic blockade. [ Time Frame: 1-2 hour ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in resting energy expenditure after achieving complete autonomic blockade. [ Time Frame: 1-2 hour ] [ Designated as safety issue: No ]

Estimated Enrollment: 288
Study Start Date: April 2003
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Part 1
Estimation of resting energy expenditure and effect of autonomic blockade with trimethaphan infusion.
Drug: Trimethaphan
Start dose: 0.05 ml/min (0.5 mg/min), IV infusion. The dose will be increased every 2-4 minutes to 1, 2, 4, and 5 mg/min. Total duration: 1 hour
Part 2 (closed)
Estimation of autonomic function and effect of autonomic blockade with trimethaphan infusion.
Drug: Trimethaphan
Start dose: 0.05 ml/min (0.5 mg/min), IV infusion. The dose will be increased every 30 minutes to 1, 2, 4, and 5 mg/min. Total duration: 1-2 hours
Part 3
Estimation of energy metabolism and effect of sympathetic stimulation with pseudoephedrine.
Drug: Pseudoephedrine
30mg tablet,VO. Single dose.
Other Name: Sudafed
Part 4a (closed)
Isoproterenol sensitivity in adipose and muscle tissue with and without systemic autonomic blockade with trimethaphan infusion.
Drug: Trimethaphan
Start dose: 0.05 ml/min (0.5 mg/min), IV infusion. The dose will be increased every 2-4 minutes to 1, 2, 4, and 5 mg/min. Total duration: 1 hour
Part 4b (closed)
Metabolic and hemodynamic response to submaximal exercise in adipose and muscle tissue with and without systemic autonomic blockade with trimethaphan infusion.
Drug: Trimethaphan
Start dose: 0.05 ml/min (0.5 mg/min), IV infusion. The dose will be increased every 2-4 minutes to 1, 2, 4, and 5 mg/min. Total duration: 1 hour

Detailed Description:

The rationale for this study is that even small alterations to energy metabolism can significantly change energy balance and body weight in the long term. We will test the hypothesis that the sympathetic nervous system (SNS) activity contributes to resting and thermogenic components of energy expenditure (EE).

This study is divided in four different parts: (1), (2), (3), (4).

Part (1): we will gauge the contribution of the sympathetic nervous system to resting energy expenditure, blood pressure, and determine differences between lean, obese, and patients with primary autonomic failure .

Part (2): we will determine the degree of sympathetic blockade by a gradual infusion of the ganglionic blocker trimethaphan.[Part 2 has been closed]

Part (3): we will determine the energy balance in patients with primary autonomic failure.

Part (4): we will determine the contribution of the sympathetic nervous system to lipolysis.[Part 4 has been closed]

Subjects selections*:

For part (1) and (2) we will study six groups of subjects (n = 40 for each group): patients with pure autonomic failure, patients with multiple system atrophy, healthy normal controls (BMI <= 25), obese controls (BMI 30-40) and obese hypertensive (BMI 30-40) and lean hypertensive (BMI 20-28). A time interval of at least 1 week is required for those subjects who wish to participate in part (1) and part (2). For part (3) we will study two groups of subjects (n=12 for each group): patients with autonomic failure, and their age sex-matched sedentary, healthy controls. For part (4) we will study two groups of subjects (n=12 for each group): healthy normal controls (BMI 20-25), obese controls (BMI 30-40).

*Part 2 and 4 have been closed.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy normal (BMI <= 25 Kg/m2), obese (BMI between 30 and 40)volunteers, lean hypertensive (BMI 20-28 Kg/m2), and obese hypertensive (BMI between 30 and 40)
  • Ages 18-60
  • Patients with pure autonomic failure and multiple system atrophy ages 18-80, referred to our service for the diagnosis and treatment of their condition, and their age sex-matched sedentary, healthy controls ages 18-80

Exclusion criteria:

  • All medical students
  • Pregnant women
  • Heart failure, symptomatic coronary artery disease, liver impairment, history of stroke or myocardial infarction, glaucoma
  • History of serious allergies or asthma
  • Subjects using beta-blockers
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00179023

Locations
United States, Tennessee
Vanderbilt University Recruiting
Nashville, Tennessee, United States, 37232
Contact: Ginnie M Farley, RAIII       adcresearch@vanderbilt.edu   
Contact: Cyndya A Shibao, MD       adcresearch@vanderbilt.edu   
Principal Investigator: Italo Biaggioni, MD         
Sub-Investigator: Cyndya A Shibao, MD         
Sub-Investigator: Alfredo Gamboa, MD         
Sub-Investigator: Andre Diedrich, MD PhD         
Sub-Investigator: Andrew Ertl, PhD         
Sub-Investigator: Kong Chen, PhD         
Sub-Investigator: Luis E okamoto         
Sponsors and Collaborators
Vanderbilt University
Investigators
Principal Investigator: Italo Biaggioni, MD Vanderbilt University
  More Information

Additional Information:
Publications:
Responsible Party: Italo Biaggioni, Professor of Medicine and Pharmacology, Vanderbilt University
ClinicalTrials.gov Identifier: NCT00179023     History of Changes
Other Study ID Numbers: 020548, HL56693
Study First Received: September 13, 2005
Last Updated: June 20, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Vanderbilt University:
OBESITY
RESTING ENERGY EXPENDITURE
SYMPATHETIC NERVOUS SYSTEM
HYPERTENSION
AUTONOMIC FAILURE

Additional relevant MeSH terms:
Shy-Drager Syndrome
Multiple System Atrophy
Hypertension
Obesity
Pure Autonomic Failure
Vascular Diseases
Cardiovascular Diseases
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Primary Dysautonomias
Autonomic Nervous System Diseases
Nervous System Diseases
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Hypotension
Pseudoephedrine
Ephedrine
Trimethaphan
Trimethaphan camsylate
Nasal Decongestants
Vasoconstrictor Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 16, 2014