Mechanism of Masked Hypertension - Intervention
Primary Purpose
Masked Hypertension
Status
Withdrawn
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Carvedilol
Amlodipine
Sponsored by
About this trial
This is an interventional treatment trial for Masked Hypertension focused on measuring Masked Hypertension, Sympathetic Activity, Sympatholytic Therapy
Eligibility Criteria
Study participants with masked hypertension i.e. controlled clinic blood pressure (BP) and uncontrolled out-of-clinic awake ambulatory BP will be enrolled.
A. Inclusion criteria.
- Adults (18-75 years of age)
- Controlled clinic BP (< 130/80 mmHg) untreated with antihypertensive medications
- Uncontrolled awake ambulatory BP (≥ 130/80 mmHg) untreated with antihypertensive medications
B. Exclusion criteria.
- Hypertensive (Clinic BP ≥ 130/80 mmHg)
- Hypotensive (Clinic BP < 90/70 mmHg)
- Bradycardic (Heart rate < 60 beats/minute)
- Heart block
- Use of an antihypertensive medication within the last 3 months
- Use of an steroid containing medications within the last 3 months
- Body mass index ≥ 30 Kg/m2
- Chronic kidney disease (Estimated GFR < 60 mL/min/1.73m2)
- Primary aldosteronism
- Renal artery stenosis
- Pheochromocytoma
- Diabetes mellitus
- Pregnant women
- Breast feeding women
- Dementia and/or cognitive impairment prohibiting consent
- History of stroke within the past 6 months
- History of unstable angina within the past 6 months
- History of myocardial infarction within the past 6 months
- Allergy or intolerance to β-blockers
- Allergy or intolerance to calcium channel blockers
Sites / Locations
- Hypertension Research Clinic at UAB
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Carvedilol 40mg Extended Release Once Daily
Amlodipine 10mg Once Daily
Arm Description
participants will be randomized to carvedilol 40 mg extended release once daily for the 1st or 2nd 4 week treatment period
participants will be randomized to amlodipine 10 mg once daily for the 1st or 2nd 4 week treatment period
Outcomes
Primary Outcome Measures
Out of clinic 24 hour ambulatory blood pressure
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
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
Difference in percent change in out-of-clinic mean asleep ambulatory BP in mmHg with carvedilol compared to amlodipine.
Secondary Outcome Measures
Out of clinic blood pressure variability
Change in out-of-clinic sympathetic activity by BP variability in mmHg with carvedilol compared to amlodipine.
Out of clinic heart rate variability
Change in out-of-clinic sympathetic activity by HR variability in beats/minute with carvedilol compared to amlodipine.
Out of clinic 24-hour urinary catecholamines
Change in out-of-clinic sympathetic activity by 24-hour urinary catecholamines levels with carvedilol compared to amlodipine.
Out of clinic 24-hour urinary metanephrines
Change in out-of-clinic sympathetic activity by 24-hour urinary metanephrines levels with carvedilol compared to amlodipine.
Full Information
NCT ID
NCT04121299
First Posted
October 7, 2019
Last Updated
October 28, 2021
Sponsor
University of Alabama at Birmingham
1. Study Identification
Unique Protocol Identification Number
NCT04121299
Brief Title
Mechanism of Masked Hypertension - Intervention
Official Title
Mechanism of Masked Hypertension - Intervention
Study Type
Interventional
2. Study Status
Record Verification Date
October 2021
Overall Recruitment Status
Withdrawn
Why Stopped
lack of funding
Study Start Date
July 2021 (Anticipated)
Primary Completion Date
June 2026 (Anticipated)
Study Completion Date
June 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Alabama at Birmingham
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
To test the hypothesis that sympatholytic antihypertensive antihypertensive therapy (αβ-blocker - carvedilol) will reduce out-of-clinic ambulatory BP to a greater extent by blocking sympathetic activity than non-sympatholytic antihypertensive medication (dihydropyridine calcium channel blocker - amlodipine) in individuals with masked hypertension.
Detailed Description
A. Participants. Study participants with masked hypertension (MH) with controlled clinic BP (< 130/80 mmHg) and uncontrolled out-of-clinic awake ambulatory BP (ABP ≥ 130/80 mmHg) untreated with antihypertensive medications will be recruited.
B. Study design. This is a double-blinded, randomized, 2-period, 2-treatment crossover clinical trial comparing sympatholytic antihypertensive agent (αβ-blocker - carvedilol 40mg extended release once daily) with non-sympatholytic control agent (dihydropyridine calcium channel blocker - amlodipine 10mg 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 ABP; sympathetic activity assessment by BP and HR variability, 24-hour urinary catecholamines and metanephrines 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 9 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. Electrolytes, kidney function and ECG will be monitored at each visit. Medication adherence will be determined at visit 2 (week 4) and visit 4 (week 12) by measuring 24-hr urinary specimens for medications and their metabolites by LC-MS/MS and by pill count and medication log.
C. Outcomes. The primary outcome is the difference in percent change in out-of-clinic mean 24-hr ABP, awake ABP and asleep ABP with carvedilol compared to amlodipine. Secondary outcomes include change in out-of-clinic sympathetic activity by BP and HR variability; and 24-hour urinary catecholamines and metanephrines.
D. Preliminary / anticipated results. We anticipate a greater reduction in out-of-clinic 24-hr, awake and asleep ABP due to blocking of sympathetic activity with carvedilol when compared to amlodipine use in individuals with MH. A statistically significant effect estimate will support our hypothesis that higher sympathetic activity contributes to MH, which can be managed by use of sympatholytic agents like carvedilol.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Masked Hypertension
Keywords
Masked Hypertension, Sympathetic Activity, Sympatholytic Therapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Carvedilol 40mg Extended Release Once Daily
Arm Type
Experimental
Arm Description
participants will be randomized to carvedilol 40 mg extended release once daily for the 1st or 2nd 4 week treatment period
Arm Title
Amlodipine 10mg Once Daily
Arm Type
Active Comparator
Arm Description
participants will be randomized to amlodipine 10 mg once daily for the 1st or 2nd 4 week treatment period
Intervention Type
Drug
Intervention Name(s)
Carvedilol
Intervention Description
Carvedilol 40mg Extended Release Once Daily
Intervention Type
Drug
Intervention Name(s)
Amlodipine
Intervention Description
Amlodipine 10mg Once Daily
Primary Outcome Measure Information:
Title
Out of clinic 24 hour ambulatory blood pressure
Description
Difference in percent change in out-of-clinic mean 24-hr ambulatory BP in mmHg with carvedilol compared to amlodipine.
Time Frame
4 weeks
Title
Out of clinic awake blood pressure
Description
Difference in percent change in out-of-clinic mean awake ambulatory BP in mmHg with carvedilol compared to amlodipine.
Time Frame
4 weeks
Title
Out of clinic asleep blood pressure
Description
Difference in percent change in out-of-clinic mean asleep ambulatory BP in mmHg with carvedilol compared to amlodipine.
Time Frame
4 weeks
Secondary Outcome Measure Information:
Title
Out of clinic blood pressure variability
Description
Change in out-of-clinic sympathetic activity by BP variability in mmHg with carvedilol compared to amlodipine.
Time Frame
4 weeks
Title
Out of clinic heart rate variability
Description
Change in out-of-clinic sympathetic activity by HR variability in beats/minute with carvedilol compared to amlodipine.
Time Frame
4 weeks
Title
Out of clinic 24-hour urinary catecholamines
Description
Change in out-of-clinic sympathetic activity by 24-hour urinary catecholamines levels with carvedilol compared to amlodipine.
Time Frame
4 weeks
Title
Out of clinic 24-hour urinary metanephrines
Description
Change in out-of-clinic sympathetic activity by 24-hour urinary metanephrines levels with carvedilol compared to amlodipine.
Time Frame
4 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Study participants with masked hypertension i.e. controlled clinic blood pressure (BP) and uncontrolled out-of-clinic awake ambulatory BP will be enrolled.
A. Inclusion criteria.
Adults (18-75 years of age)
Controlled clinic BP (< 130/80 mmHg) untreated with antihypertensive medications
Uncontrolled awake ambulatory BP (≥ 130/80 mmHg) untreated with antihypertensive medications
B. Exclusion criteria.
Hypertensive (Clinic BP ≥ 130/80 mmHg)
Hypotensive (Clinic BP < 90/70 mmHg)
Bradycardic (Heart rate < 60 beats/minute)
Heart block
Use of an antihypertensive medication within the last 3 months
Use of an steroid containing medications within the last 3 months
Body mass index ≥ 30 Kg/m2
Chronic kidney disease (Estimated GFR < 60 mL/min/1.73m2)
Primary aldosteronism
Renal artery stenosis
Pheochromocytoma
Diabetes mellitus
Pregnant women
Breast feeding women
Dementia and/or cognitive impairment prohibiting consent
History of stroke within the past 6 months
History of unstable angina within the past 6 months
History of myocardial infarction within the past 6 months
Allergy or intolerance to β-blockers
Allergy or intolerance to calcium channel blockers
Facility Information:
Facility Name
Hypertension Research Clinic at UAB
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Will adhere to the NIH Data Sharing and Implementation policy:
https://grants.nih.gov/grants/policy/data_sharing/data_sharing_guidance.htm
Data Sharing: Unpublished research data will be presented at scientific meetings. These regularly include American Heart Association Council on Hypertension Scientific Sessions and Southern Society of Clinical Investigators-southern regional meeting. Moreover, unpublished data, including methodologies and datasets will be uploaded to RedCap with access granted to mentor, co-mentors and members of mentoring committee. All data acquired will be shared and made publicly available through publication in the peer-reviewed literature.
IPD Sharing Time Frame
Research data will be shared with non-participating investigators once the data are accepted for publication.
IPD Sharing Access Criteria
All accepted manuscripts will be submitted electronically to PubMed Central (PMC) via the NIH Manuscript Submission (NIHMS) system according to journal policy and NIH agreements. Through the Freedom of Information Act, the data in the publications and the raw data documents will be made available upon written request.
Learn more about this trial
Mechanism of Masked Hypertension - Intervention
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