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| Sponsored by: |
Vanderbilt University |
| Information provided by: | Vanderbilt University |
| ClinicalTrials.gov Identifier: | NCT00179023 |
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 |
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Obesity Hypertension Pure Autonomic Failure Shy-Drager Syndrome |
Drug: Trimethaphan Drug: Pseudoephedrine |
Phase I Phase II |
| Genetics Home Reference related topics: | familial paroxysmal nonkinesigenic dyskinesia |
| MedlinePlus related topics: | High Blood Pressure Obesity |
| ChemIDplus related topics: | Ephedrine Ephedrine Hydrochloride Pseudoephedrine hydrochloride Pseudoephedrine Sulfate Trimethaphan Trimethaphan camsylate |
| Study Type: | Interventional |
| Study Design: | Diagnostic, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment |
| Official Title: | The Autonomic Nervous System and Obesity |
| Estimated Enrollment: | 288 |
| Study Start Date: | April 2003 |
| Estimated Study Completion Date: | August 2010 |
| Estimated Primary Completion Date: | July 2009 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
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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
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.
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Part 4a
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
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Part 4b
Metabolic and hemodynamic response to submaximal exercise 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
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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 (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.
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).
Eligibility
| Ages Eligible for Study: | 18 Years to 80 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
Exclusion criteria:
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 | |||||
| Vanderbilt University |
| Principal Investigator: | Italo Biaggioni, MD | Vanderbilt University |
More Information
Autonomic dysfunction center at Vanderbilt University
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| Responsible Party: | Vanderbilt University ( Italo Biaggioni ) |
| Study ID Numbers: | 020548, HL56693 |
| First Received: | September 13, 2005 |
| Last Updated: | September 17, 2008 |
| ClinicalTrials.gov Identifier: | NCT00179023 |
| Health Authority: | United States: Food and Drug Administration |
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