The Autonomic Nervous System and Obesity
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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 |
- Change in supine systolic blood pressure after achieving complete ganglionic blockade. [ Time Frame: 1-2 hour ] [ Designated as safety issue: No ]
- 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 2013 |
| Estimated Primary Completion Date: | October 2013 (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.
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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
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Part 2 (closed)
Estimation of autonomic function and effect of autonomic blockade with trimethaphan infusion.
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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
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Part 3
Estimation of energy metabolism and effect of sympathetic stimulation with pseudoephedrine.
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Drug: Pseudoephedrine
30mg tablet,VO. Single dose.
Other Name: Sudafed
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Part 4a (closed)
Isoproterenol sensitivity in adipose and muscle tissue with and without systemic autonomic blockade with trimethaphan infusion.
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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 |
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| 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 | |
| Principal Investigator: | Italo Biaggioni, MD | Vanderbilt University |
More Information
Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| 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: | May 10, 2012 |
| 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:
|
Hypertension Obesity Shy-Drager Syndrome Multiple System Atrophy 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 May 22, 2013