Mechanism of Masked Hypertension – Intervention

Overview

To test the hypothesis that sympatholytic antihypertensive therapy (αβ-blocker – carvedilol) will reduce out-of-clinic 24-hr BP to a greater extent by blocking sympathetic activity than non-sympatholytic antihypertensive medication (dihydropyridine calcium channel blocker – amlodipine) in individuals with Masked Hypertension.

Full Title of Study: “Mechanism of Masked Hypertension – Intervention”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Crossover Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: March 2025

Detailed Description

Study participants with Masked Hypertension who have controlled clinic BP (< 130/80 mmHg) but uncontrolled out-of-clinic 24-hr ambulatory BP (>= 125/75) will be enrolled. This is a double-blinded randomized 2-period, 2 treatment crossover clinical trial comparing sympatholytic antihypertensive agent (αβ-blocker – carvedilol 20mg extended release once daily) with non-sympatholytic control agent (dihydropyridine calcium channel blocker – amlodipine 5mg once daily) in individuals with MH. All study participants will undergo out-of-clinic 24hr ABP with actigraphy monitoring for 24-hr, awake and asleep BP; sympathetic activity assessment (by BP and HR variability) at baseline and after intervention. In order to avoid selection bias, patients will be randomized to their initial therapy. Patients and study personnel will be blinded to the treatment group in order to minimize information bias. An investigator without direct study involvement will be assigned the task of ensuring correct dispensing of the study medication, which will be prepared as matching capsules by the UAB Pharmacy – Investigational Drug Service. After 4 weeks of initial treatment, both treatment groups will undergo a 1-month washout where no study medication is given in order to prevent a carryover effect. The study medication will be taken in the morning between 6 and 8 am except for study visit days. A crossover design is chosen to minimize differences between study groups, as participants will act as their own controls. RFP to monitor electrolytes, kidney function and ECG to detect bradycardia and/or heart block will be done at each visit.

Interventions

  • Drug: Carvedilol
    • participants will be randomized to carvedilol or amlodipine for the 1st or 2nd 4 week treatment period
  • Drug: Amlodipine
    • participants will be randomized to carvedilol or amlodipine for the 1st or 2nd 4 week treatment period

Arms, Groups and Cohorts

  • Active Comparator: Carvedilol 20mg Extended Release Once Daily
    • participants will be randomized to carvedilol 20 mg extended release once daily for the 1st or 2nd 4 week treatment period
  • Active Comparator: Amlodipine 5mg Once Daily
    • participants will be randomized to amlodipine 5 mg once daily for the 1st or 2nd 4 week treatment period

Clinical Trial Outcome Measures

Primary Measures

  • out of clinic 24 hour ambulatory blood pressure
    • Time Frame: 4 weeks
    • difference in percent change in out-of-clinic mean 24-hr ambulatory BP in mmHg with carvedilol compared to amlodipine.
  • out of clinic awake blood pressure
    • Time Frame: 4 weeks
    • difference in percent change in out-of-clinic mean awake ambulatory BP in mmHg with carvedilol compared to amlodipine.
  • out of clinic asleep blood pressure
    • Time Frame: 4 weeks
    • difference in percent change in out-of-clinic mean asleep ambulatory BP in mmHg with carvedilol compared to amlodipine.

Secondary Measures

  • out of clinic blood pressure variability
    • Time Frame: 4 weeks
    • decrease in out-of-clinic sympathetic activity by BP variability in mmHg with carvedilol compared to amlodipine.
  • out of clinic heart rate variability
    • Time Frame: 4 weeks
    • decrease in out-of-clinic sympathetic activity by HR variability in beats/minute with carvedilol compared to amlodipine.

Participating in This Clinical Trial

Inclusion Criteria

  • Patients with controlled BP (<130/80 mmHg) in clinic but uncontrolled BP (130/80 mmHg) by 24-hour ambulatory BP monitor

Exclusion Criteria

  • Hypertensive (Clinic BP ≥ 130/80 mmHg)
  • Hypotensive (Clinic BP < 90/70 mmHg)
  • Bradycardic (Heart rate < 60 beats/minute)
  • Use of an antihypertensive medication within the last 3 months
  • Use of an steroid medications within the last 3 months
  • Body mass index ≥ 30 Kg/m2
  • Estimated GFR < 60 mL/min/1.73m2
  • Primary aldosteronism
  • Renal artery stenosis
  • Pheochromocytoma
  • Diabetes mellitus
  • Pregnant or breast feeding woman
  • Dementia or cognitive impairment prohibiting consent
  • History of stroke, unstable angina, or myocardial infarction within the past 6 months
  • Allergy or intolerance to β-blockers or dihydropyridine calcium channel blockers

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 75 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • University of Alabama at Birmingham
  • Provider of Information About this Clinical Study
    • Principal Investigator: Mohammed Siddiqui, MD, Postdoctoral Fellow, Vascular Biology and Hypertension Program, Division of Cardiovascular Disease – University of Alabama at Birmingham

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