The Autonomic Nervous System and Obesity

NCT00179023 | Completed Phase 1

• 2 other identifiers: 020548HL56693
• Study Type: interventional
• Target: 128
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

OBESITY; HYPERTENSION; PURE AUTONOMIC FAILURE; SHY-DRAGER SYNDROME

Keywords

OBESITY; RESTING ENERGY EXPENDITURE; SYMPATHETIC NERVOUS SYSTEM; HYPERTENSION; AUTONOMIC FAILURE

Outcome Measures

Primary Outcomes (1)

• Change in supine systolic blood pressure after achieving complete ganglionic blockade.

  1-2 hour

Secondary Outcomes (1)

• Change in resting energy expenditure after achieving complete autonomic blockade.

  1-2 hour

Study Arms (5)

Part 1

OTHER

Estimation of resting energy expenditure and effect of autonomic blockade with trimethaphan infusion.

Drug: Trimethaphan

Part 2 (closed)

OTHER

Estimation of autonomic function and effect of autonomic blockade with trimethaphan infusion.

Drug: Trimethaphan

Part 3

OTHER

Estimation of energy metabolism and effect of sympathetic stimulation with pseudoephedrine.

Drug: Pseudoephedrine

Part 4a (closed)

OTHER

Isoproterenol sensitivity in adipose and muscle tissue with and without systemic autonomic blockade with trimethaphan infusion.

Drug: Trimethaphan

Part 4b (closed)

OTHER

Metabolic and hemodynamic response to submaximal exercise in adipose and muscle tissue with and without systemic autonomic blockade with trimethaphan infusion.

Drug: Trimethaphan

Interventions

Trimethaphan DRUG

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 1; Part 4a (closed); Part 4b (closed)

Pseudoephedrine DRUG

30mg tablet,VO. Single dose.

Also known as: Sudafed

Part 3

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Vanderbilt University: lead

Study Sites (1)

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

Related Publications (2)

• Shibao C, Gamboa A, Diedrich A, Ertl AC, Chen KY, Byrne DW, Farley G, Paranjape SY, Davis SN, Biaggioni I. Autonomic contribution to blood pressure and metabolism in obesity. Hypertension. 2007 Jan;49(1):27-33. doi: 10.1161/01.HYP.0000251679.87348.05. Epub 2006 Nov 20.

  PMID: 17116758 RESULT

• Shibao C, Buchowski MS, Chen KY, Yu C, Biaggioni I. Chronic sympathetic attenuation and energy metabolism in autonomic failure. Hypertension. 2012 May;59(5):985-90. doi: 10.1161/HYPERTENSIONAHA.111.190157. Epub 2012 Apr 2.

  PMID: 22469621 RESULT

MeSH Terms

Conditions

Obesity; Hypertension; Pure Autonomic Failure; Shy-Drager Syndrome

Interventions

Trimethaphan; Pseudoephedrine

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Vascular Diseases; Cardiovascular Diseases; Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases; Multiple System Atrophy; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Movement Disorders; Hypotension

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Phenethylamines; Ethylamines

Study Officials

• Italo Biaggioni, MD

  Vanderbilt University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine and Pharmacology

Study Record Dates

• First Submitted: September 13, 2005
• First Posted: September 15, 2005
• Study Start: April 1, 2003
• Primary Completion: January 1, 2017
• Study Completion: January 1, 2017
• Last Updated: March 1, 2018

Record last verified: 2018-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)