Trial record 5 of 22 for:    Open Studies | "Prehypertension"

Vascular Dysfunction in Human Obesity Hypertension (VANISH)

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by University of Iowa
Sponsor:
Collaborators:
American Heart Association
Information provided by (Responsible Party):
University of Iowa
ClinicalTrials.gov Identifier:
NCT01983462
First received: October 30, 2013
Last updated: November 6, 2013
Last verified: November 2013
  Purpose

The purpose of the study is to test the effects of: 1) blocking sympathetic nerve activity with a drug called clonidine, and 2) by blocking a kidney protein called renin, and on blood vessel function and muscle nerve activity in adults who are obese and have high blood pressure.

Years 1 and 2: The 1st cohort of subjects will consist of 69 healthy young men and women age 18-79 years who are obese, defined as a body mass index > or = to 30 kg/m2, who have untreated systolic hypertension (systolic blood pressure > or = to 130 - <180 mmHg- average of at least 3 measurements 2 min apart after 10 min seated resting position). These 69 subjects will then be randomized to 3 treatment arms: clonidine (0.1 mg/day), hydrochlorothiazide (25 mg/day) or placebo for 4 weeks in years 1 and 2. All tablets will be encapsulated by to look identical. Subjects will randomly (1:1:1) receive one of the following combinations in a double-blind, placebo-controlled design:

  1. Oral clonidine (0.1 mg twice/day)
  2. Oral hydrochlorothiazide (12.5 mg twice/day)
  3. Oral placebo

In addition to 69 healthy young men and women, we will also enroll 15 obese adults with 'normal/optimal' systolic blood pressure (<120mmHg) who will undergo baseline testing only (Visits 1, 2 and 3).

Years 3 and 4: A 2nd cohort of subjects (n=42) will be randomized to aliskiren (150 mg/day), hydrochlorothiazide (25 mg/day) or placebo for 4 weeks. All tablets will be encapsulated to look identical. Subjects will receive one of the following in a randomized, double-blind, placebo-controlled design:

  1. Oral Aliskiren(150 mg/day- once per day)
  2. Oral Hydrochlorothiazide (12.5 mg twice/day)
  3. Oral placebo

Condition Intervention Phase
Obesity
Prehypertension
Hypertension
Drug: Clonidine
Drug: Hydrochlorothiazide
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Vascular Dysfunction in Human Obesity Hypertension: Integrative Role of Sympathetic and Renin-Angiotensin Systems

Resource links provided by NLM:


Further study details as provided by University of Iowa:

Primary Outcome Measures:
  • Forearm endothelium-dependent dilation (EDD) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Forearm blood flow responses to intra-brachial artery infusions of acetylcholine (ml/100 ml forearm volume/min)

  • Forearm endothelium-independent dilation (EID) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Forearm blood flow responses to intra-brachial artery infusions of sodium nitroprusside (ml/100 ml forearm volume/min)


Secondary Outcome Measures:
  • Muscle sympathetic nerve activity [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Peroneal nerve activity via microneurography (bursts/min; bursts per 100 beats)

  • Endothelial cell oxidative stress and RAS proteins [ Time Frame: 4 weeks ]

Estimated Enrollment: 126
Study Start Date: October 2013
Estimated Primary Completion Date: September 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Clonidine
Oral 0.2 mg/day (0.1 mg bid)for 4 weeks
Drug: Clonidine
Other Name: Catapress
Active Comparator: Hydrochlorothiazide
Oral, 12.5 mg/day qd, 4 weeks
Drug: Hydrochlorothiazide
Placebo Comparator: Placebo Drug: Placebo

  Eligibility

Ages Eligible for Study:   18 Years to 79 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Willing and able to provide written, signed informed consent after the nature of the study has been explained, and prior to any research-related procedures.
  • Systolic blood pressure >/= 130 mmHg and <180 mmHg
  • Age is > or = 18 and < or = 79 years of age
  • Weight stable (+/- 5 lbs) for the previous 3 months
  • Healthy, as determined by health history questionnaire, blood chemistries, 12-lead ECG
  • Blood chemistries indicative of normal renal (creatinine <2.0 mg/dl), liver (<3 times upper limit for ALT, AST), and thyroid function (TSH between 0.4 - 5.0 mU/L)
  • If currently receiving treatment with or taking any of the following supplements, be willing and able to discontinue taking them for 2 weeks prior and throughout the treatment period: Vitamin C, E or other multivitamins containing vitamin C or E; or omega-3 fatty acids.
  • No history of cardiovascular disease (e.g., heart attack, stroke, heart failure, valvular heart disease, cardiomyopathy), Type 1 or Type 2 diabetes, or peripheral arterial disease
  • Non-smokers, defined as no history of smoking or no smoking for at least the past 1 year
  • Normal resting 12-lead ECG (no evidence of myocardial infarction, left ventricular hypertrophy, left-bundle branch block, 2nd or 3rd degree AV block, atrial fibrillation/flutter)

Exclusion Criteria:

  • Systolic blood pressure >/=180 mmHg or diastolic blood pressure >110 mmHg
  • History of cardiovascular disease such as heart angioplasty/stent or bypass surgery, myocardial infarction, stroke, heart failure with or without left ventricular ejection fraction <40%, cardiomyopathy, valvular heart disease, cardiomyopathy, heart transplantation, Type 2 and Type 1 diabetes
  • Smoking or history of smoking within past one year
  • History of gastric ulcers, bleeding disorders, dyspepsia, severe gastroesophageal reflux disease (GERD), or metabolic acidosis
  • History of chronic obstructive pulmonary disease (COPD)
  • Abnormal resting 12-lead ECG (e.g., evidence of myocardial infarction, left ventricular hypertrophy, left-bundle branch block, 2nd or 3rd degree AV block, atrial fibrillation/flutter)
  • Serious neurologic disorders including seizures
  • History of renal failure, dialysis or kidney transplant
  • Serum creatinine > 2.0 mg/dL, or hepatic enzyme (ALT/AST) concentrations > 3 times the upper limit of normal
  • History of HIV infection, hepatic cirrhosis, other preexisting liver disease, or positive HIV, Hepatitis B or C test at screening.
  • Use of any investigational product or investigational medical device within 30 days prior to screening, or requirement for any investigational agent prior to completion of all scheduled study assessments.
  • History of recent chicken pox, shingles or influenza (ie., risk of Reye's syndrome)
  • Recent flu-like symptoms within the past 2 weeks
  • Pregnant or breastfeeding at screening, or planning to become pregnant (self or partner) at any time during the study. A urinary pregnancy test will be done on all females. If test is positive, the subject will be excluded.
  • Women with history of hormone replacement therapy within the past 6 months
  • History of rheumatoid arthritis, Grave's disease, systemic lupus erythematosis, and Wegener's granulomatosis;
  • Taking lipid lowering (e.g., statins, niacin), glycemic control (e.g. metformin, insulin), anticoagulation, anti-seizure, anti-depression or antipsychotic agents
  • History of co-morbid condition that would limit life expectancy to < 6 months.
  • Taking chronic non-steroidal anti-inflammatory drugs (NSAIDS) such as aspirin, indomethacin, naproxen, acetaminophen (Tylenol), ibuprofen (Advil, Motrin) and not able or willing to go off of for 2 weeks prior and during the study
  • Taking cox-2 inhibitors (Celebrex, Vioxx, etc) or allopurinol (Zyloprim, Lopurin, Allopurin)
  • Taking blood thinners such as coumadin (Warfarin), enoxaparin (Lovenox); clopidogrel (Plavix); dipyridamole (Persantine); heparin;
  • Taking diabetic medications (Metformin, glyburide, insulin, etc.), thiazolidinediones (Avandia, Rezulin, Actos);
  • Taking steroids or biologics : corticosteroids (prednisone); methotrexate, infliximab (Remicade), etanercept (Enbrel); anakinra;
  • Taking thyroid medications such as levothyroxine (Levoxyl, Synthroid, Levoxyl, Unithroid); Levodopa;
  • Taking Phosphodiesterase (PDE) 5 inhibitors (e.g., Viagra®, Cialis®, Levitra®, or Revatio®); PDE 3 inhibitors (e.g., cilostazol, milrinone, or vesnarinone); lithium
  • May participate if no use of the following medications in the 48 hours prior to experimental visits: naproxen (Aleve), acetaminophen (Tylenol), ibuprofen (Advil, Motrin), other any non-steroidal anti-inflammatory drugs (NSAIDS)
  • Vulnerable populations (prisoners, etc.)
  • Any condition that, in the view of the PI, places the subject at high risk of poor treatment compliance or of not completing the study.
  • History of alcohol abuse or >10 alcoholic units per week (1 unit= 1 beer, 1 glass of wine, 1 mixed cocktail containing 1 oz alcohol)
  • On weight loss drugs (e.g., Xenical (orlistat), Meridia (sibutramine), Acutrim (phenylpropanol-amine), or similar over-the-counter medications) within 3 months of screening
  • Any surgery within 30 days of screening
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01983462

Contacts
Contact: Veronica Howsare veronica-howsare@uiowa.edu

Locations
United States, Iowa
University of Iowa Recruiting
Iowa City, Iowa, United States, 52240
Sponsors and Collaborators
University of Iowa
American Heart Association
Investigators
Principal Investigator: Gary L Pierce, PhD University of Iowa
  More Information

No publications provided

Responsible Party: University of Iowa
ClinicalTrials.gov Identifier: NCT01983462     History of Changes
Other Study ID Numbers: 201307779
Study First Received: October 30, 2013
Last Updated: November 6, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Iowa:
Prehypertension
Hypertension
Obese
Sympathetic Nervous System
renin-angiotensin system
Endothelial function

Additional relevant MeSH terms:
Prehypertension
Hypertension
Obesity
Vascular Diseases
Cardiovascular Diseases
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Clonidine
Hydrochlorothiazide
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Antihypertensive Agents
Cardiovascular Agents
Sympatholytics
Autonomic Agents
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Diuretics

ClinicalTrials.gov processed this record on July 31, 2014