Pathophysiology of Cardiometabolic Risk Factors in African Americans

NCT01122407 | Completed Phase 1 DMC

• 2 other identifiers: 091282K23HL103976-06
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

The overall goal of this proposal is to determine the autonomic and nitric oxide contribution in the pathogenesis of hypertension and insulin resistance in obese African American women. For this purpose we will use two non-FDA approved drugs: Trimethaphan IND# 63826 Approval date 12/20/2001 L-NMMA IND# 41735 Approval date 09/1993

Conditions

Obesity; Hypertension

Outcome Measures

Primary Outcomes (1)

• change in systolic blood pressure in response to trimethaphan, as a measurement of the tonic sympathetic contribution to blood pressure.

  Will infuse trimethaphan for until complete autonomic blockade is achieved.

  30 minutes after initiation of Trimethaphan infusion

Secondary Outcomes (1)

• increase in systolic blood pressure induced by NOS inhibition with 250 ug/kg/min L-NMMA during autonomic withdrawal with trimethaphan.

  within 30 minutes

Study Arms (2)

trimethaphan

EXPERIMENTAL

Trimethaphan infusion doses of 4 mg/min

Drug: Trimethaphan

Trimethaphan plus L-NMMA

EXPERIMENTAL

Trimethaphan infusion 4 mg/min L-NMMA (L-NG-monomethyl Arginine citrate) infusion 250 mpg/kg/min A small group of arm 1 will receive both drugs.

Drug: L-NMMA; Drug: Trimethaphan

Interventions

L-NMMA DRUG

L-NMMA 250 ug/Kg/min

Trimethaphan plus L-NMMA

Trimethaphan DRUG

Will infuse trimethaphan for until complete autonomic blockade is achieved.

Trimethaphan plus L-NMMA; trimethaphan

Eligibility Criteria

• Age: 30 Years - 50 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Race will be self-defined, but only subjects who report both parents of the same race will be included.
• All subjects will be pre-menopausal. Age 30-50 years old. We will recruit subjects with wide range of BMI 30-45 kg/m2. Both hypertensives and non-hypertensives will be recruited Hypertension will be defined as a seated blood pressure \>130/85 determined in at least two occasions, and therefore, includes patients with "pre-hypertension".
• Subjects will be required to have a negative serum/urine pregnancy test. In addition, they will be asked to use a reliable contraceptive method prior to enrollment as determined by the PI (Dr. Cyndya Shibao)

You may not qualify if:

• Previous allergic reactions to any of the study medications (trimethaphan, L-NMMA, phenylephrine) or inability to take study medications as prescribed during the course of the study.
• Use of pacemaker or any metal implant NOT COMPATIBLE WITH MRI (artificial heart valves, implanted drug infusion ports, artificial limb, implanted nerve stimulator, metal pins, screws, plates, surgical staples).
• Type 1 or 2 diabetes mellitus as defined by a fasting glucose of 126 mg/dl or greater or the use of anti-diabetic medication.
• Cardiovascular disease such as myocardial infarction within 6 months prior to enrollment, presence of angina pectoris, significant arrhythmia, congestive heart failure (LV hypertrophy acceptable), deep vein thrombosis, pulmonary embolism, second or third degree heart block, mitral valve stenosis, aortic stenosis or hypertrophic cardiomyopathy.
• History of smoking or current smokers. Significant weight change \>5% from baseline in the past three months. Pregnancy or breast-feeding. History of serious neurological disease such as cerebral hemorrhage stroke, transient ischemic attack.
• History or presence of immunological or hematological disorders. Clinical significant gastrointestinal impairment that could interfere with drug absorption.
• Impaired hepatic function (aspartate amino transaminase \[AST\] and/or alanine amino transaminase \[ALT\] \>1.5X upper limit of normal range).
• Impaired renal function (estimated glomerular filtration rate (eGFR) of \<60mL/min).
• Any underlying or acute disease requiring regular medication which could possibly pose a threat to the subject or make implementation of the protocol or interpretation of the study results difficult.
• History of alcohol or drug abuse. Mental conditions rendering the subject unable to understand the nature, scope and possible consequences of the study.
• Inability to comply with the protocol, e.g. uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study.

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Related Publications (1)

• Rahman S, Gamboa A, Saleem M, Kulapatana S, Diedrich A, Biaggioni I, Kirabo A, Shibao CA. Complete autonomic blockade reveals nitric oxide contribution to blood pressure regulation in obese Black women. Clin Auton Res. 2024 Aug;34(4):427-436. doi: 10.1007/s10286-024-01050-3. Epub 2024 Aug 1.

  PMID: 39090323 DERIVED

MeSH Terms

Conditions

Obesity; Hypertension

Interventions

omega-N-Methylarginine; Trimethaphan

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

Intervention Hierarchy (Ancestors)

Arginine; Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Amino Acids, Essential; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Cyndya Shibao, MD

  Vanderbilt University

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: May 10, 2010
• First Posted: May 13, 2010
• Study Start: January 1, 2010
• Primary Completion: November 1, 2016
• Study Completion: November 1, 2016
• Last Updated: January 18, 2017

Record last verified: 2017-01

Locations

US (1)