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Trial record 81 of 112 for:    EPLERENONE

The Role of Aldosterone on Augmented Exercise Pressor Reflex in Hypertension

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ClinicalTrials.gov Identifier: NCT01996449
Recruitment Status : Recruiting
First Posted : November 27, 2013
Last Update Posted : January 16, 2019
Sponsor:
Information provided by (Responsible Party):
Wanpen Vongpatanasin, University of Texas Southwestern Medical Center

Tracking Information
First Submitted Date  ICMJE November 21, 2013
First Posted Date  ICMJE November 27, 2013
Last Update Posted Date January 16, 2019
Study Start Date  ICMJE July 2013
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 30, 2015)
  • Muscle sympathetic nerve activity during exercise [ Time Frame: 8 weeks after initiation of spironolactone; ]
  • Muscle sympathetic nerve activity during exercise [ Time Frame: 8 weeks after initiating Amlodipine ]
Original Primary Outcome Measures  ICMJE
 (submitted: November 26, 2013)
  • Muscle sympathetic nerve activity during exercise [ Time Frame: 8 weeks after initiation of spironolactone ]
  • Muscle sympathetic nerve activity during exercise [ Time Frame: 8 weeks after initiating Amlodipine ]
Change History Complete list of historical versions of study NCT01996449 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Role of Aldosterone on Augmented Exercise Pressor Reflex in Hypertension
Official Title  ICMJE The Role of Aldosterone on Augmented Exercise Pressor Reflex in Hypertension
Brief Summary Hypertensive patients often show an exaggerated rise in blood pressure during exercise through overactivity of the exercise pressor reflex. An increasing body of evidence suggests a role for aldosterone in augmenting the exercise pressor reflex in hypertensive humans. We hypothesize that this effect of aldosterone is mediated by its direct action on the central nervous system and that administration of mineralocorticoid receptor antagonists constitute an effective treatment for EPR overactivity in hypertension, independent of reductions in resting BP.
Detailed Description

Hypertensive patients are known to display exaggerated rise in blood pressure (BP) during exercise but the underlying mechanisms are poorly understood.

Traditionally, muscle afferents were dichotomized as metaboreceptors, which are activated slowly and only during intense or ischemic muscle contraction, or mechanoreceptors, which respond quickly to even mild deformation of their receptive fields. The increase in sympathetic nerve activity and BP caused by activation of these receptors, known as exercise pressor reflex, is normally buffered by activation arterial baroreceptors, which are reset to operate at higher BP range but at the same level of sensitivity. Mechanisms responsible for overactive exercise pressor reflex in hypertension remain unknown, but an increasing body of evidence suggested a role for aldosterone in regulating resting central sympathetic outflow in both hypertensive rats and humans.

Experiments will be performed on 3 groups of subjects 1) stage I (140-159/90-99 mmHg) subjects with essential hypertension, 2) stage I hypertensive subjects with Primary Aldosteronism (PA), and 3) normotensive controls. All participants will attend a baseline study visit, which will include a physical examination, a medical history review, vital sign measurements, and blood and urine collection. Small electrodes will be used to measure muscle nerve activity while the subjects perform a series of exercises that include passive arm cycling, active arm cycling, rhythmic hand grip, sustained hand grip and cold pressor test. Muscle blood flow will be measured before and after hand grip exercises.

A subgroup of subjects with essential hypertension and PA will be assigned to receive Eplerenone or Amlodipine on a randomized, double-blinded design. Participants will attend two weeks visits over a period of 16 weeks. Study visits include measurement of vital signs and blood samples collection. After completing 8 weeks on each medication, muscle nerve activity will be measured while performing the same exercises described in the baseline study visit.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Condition  ICMJE Hypertension
Intervention  ICMJE
  • Drug: Eplerenone
    The subject will be started on Eplerenone (Inspra) 50-200mg daily, which he or she will continue for a period of 8 weeks. Following the 8-week treatment period, the procedures listed below will be performed. After completion of the study procedures, the medication will be discontinued
    Other Name: Inspra
  • Drug: Amlodipine
    The subject will be started on Amlodipine (Norvasc) 2.5 -10mg daily, which he or she will continue for a period of 8 weeks. Following the 8-week treatment period, the procedures listed below will be performed. After completion of the study procedures, the medication will be discontinued.
    Other Name: Norvasc
  • Procedure: Microneurography
    Investigators will measure sympathetic nerve activity from the peroneal nerve by inserting a tiny needle directly into the nerve in the leg. Investigators will localize the nerve by electrical stimulation over the skin using a blunt probe. With this stimulation, subject will notice either involuntary twitching or a tingling sensation, which may be annoying but not painful. Investigators will then introduce a tiny, sterile wire needle (an electrode) through the skin at the same location. When the tip of the needle enters the nerve, subjects may again notice involuntary muscle twitches or tingling in the leg. Investigators will then turn the electrical stimulator off and make minor adjustments in the position of the needle until investigators begin to record the nerve signals. The recording needle will remain in position throughout the study.
    Other Name: Assessment of sympathetic nerve activity (SNA)
  • Procedure: Rhythmic handgrip exercise
    Subjects will perform a rhythmic handgrip exercise at 30% or 45% of maximal voluntary contraction for 3 minutes. Investigators will measure cardiac output (non-invasive impedance plethysmography), blood pressure, and sympathetic nerve activity (SNA) at baseline and following this handgrip exercise
  • Procedure: Sustained hand grip
    Subjects will perform a sustained handgrip exercise at 30% of maximal voluntary contraction for 3 minutes. Investigators will measure cardiac output (non-invasive impedance plethysmography), blood pressure, and sympathetic nerve activity (SNA) at baseline and following this handgrip exercise.
  • Procedure: Forearm blood flow
    Using high-resolution ultrasound, investigators will measure skeletal muscle blood flow in the forearm at rest, following sustained handgrip exercise
  • Procedure: Arm cycling exercise
    Subjects will perform a cycling arm exercise with a stationary cycling device. Investigators will measure cardiac output (non-invasive impedance plethysmography), blood pressure, and sympathetic nerve activity (SNA) at baseline and following this exercise.
  • Procedure: Cold Pressor test
    Subjects will place hand in cold water with ice for 3 minutes. Investigators will measure cardiac output (non-invasive impedance plethysmography), blood pressure, and sympathetic nerve activity (SNA) at baseline, during and 2 minutes after the test.
Study Arms  ICMJE
  • Active Comparator: Initial treatment with Amlodipine
    The subject will be started on Amlodipine 2.5-10 mg daily, which he or she will continue for a period of 12 weeks. Following the 12-week treatment period, the procedures listed below will be performed. After completion of the study procedures, the medication will be discontinued. The subject will be started on Eplerenone 50 - 200 mg daily, which he or she will continue for a period of 8 weeks. Following the 8 week treatment period, the procedures listed below will be performed. After completion of the study procedures, the medication will be discontinued.
    Interventions:
    • Drug: Eplerenone
    • Drug: Amlodipine
    • Procedure: Microneurography
    • Procedure: Rhythmic handgrip exercise
    • Procedure: Sustained hand grip
    • Procedure: Forearm blood flow
    • Procedure: Arm cycling exercise
    • Procedure: Cold Pressor test
  • Active Comparator: Initial treatment with Eplerenone
    The subject will be started on Eplerenone 50 - 200 mg daily, which he or she will continue for a period of 12 weeks. Following the 12-week treatment period, the procedures listed below will be performed. After completion of the study procedures, the medication will be discontinued. The subject will be started on Amlodipine 2.5-10 mg daily, which he or she will continue for a period of 8 weeks. Following the 8 week treatment period, the procedures listed below will be performed. After completion of the study procedures, the medication will be discontinued.
    Interventions:
    • Drug: Eplerenone
    • Drug: Amlodipine
    • Procedure: Microneurography
    • Procedure: Rhythmic handgrip exercise
    • Procedure: Sustained hand grip
    • Procedure: Forearm blood flow
    • Procedure: Arm cycling exercise
    • Procedure: Cold Pressor test
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 26, 2013)
3
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2019
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Experiments will be performed on 3 groups of nondiabetic human subjects:
  • 1) stage I (140-159/90-99 mmHg) subjects with essential hypertension.
  • 2) stage I hypertensive subjects with primary aldosteronism
  • 3) normotensive controls.

Exclusion Criteria:

  • 1) Any evidence of cardiopulmonary disease, left ventricular hypertrophy or systolic dysfunction by echocardiography.
  • 2) Blood pressure averaging ≥160/100 mmHg
  • 3) Estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73m2
  • 4) Diabetes mellitus or other systemic illness
  • 5) Pregnancy
  • 6) Hypersensitivity to nitroprusside, phenylephrine, amlodipine or eplerenone
  • 7) Any history of substance abuse or current cigarette use
  • 8) Any history of psychiatric illness
  • 9) History of malignancy
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Debbie Arbique, DNP (214)648-3188 debbie.arbique@utsouthwestern.edu
Contact: Poghni Peri-Okonny, MD 2146483180 poghni.peri-okonny@utsouthwestern.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01996449
Other Study ID Numbers  ICMJE R01HL113738( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Wanpen Vongpatanasin, University of Texas Southwestern Medical Center
Study Sponsor  ICMJE University of Texas Southwestern Medical Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Wanpen Vongpatanasin, MD UT Southwestern Medical Center
PRS Account University of Texas Southwestern Medical Center
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP