African American Study of Kidney Disease and Hypertension ABPM Pilot Study

4. Methods 4a. Overview The study will be conducted in participants in the African-American Study of Kidney Disease (AASK) Cohort study as a randomized three period cross-over trial.

Eighty five percent of AASK cohort participants are currently on an ACE inhibitor or angiotensin receptor blocker; the most commonly used ACE inhibitor is ramipril. The new strategies proposed in this pilot study will remain ramipril-based, to maintain the overall blood pressure control achieved thus far.

The antihypertensive regimens proposed are as follows:

• AM dosing of ramipril and other once daily medications in the participants antihypertensive regimen (termed USUAL),
• Bedtime dosing of ramipril and other once a day medications in the participant's antihypertensive regimen (termed HS-DOSING), and
• their current antihypertensive regimen plus an additional antihypertensive agent dosed at bed time; the choice of the additional agent will be tailored based on prespecified clinical guidelines (termed ADD-ON DOSING)

The "usual arm" serves as the comparator arm. The "hs dosing" and "add-on dosing" arms test practical strategies that could be tested in a subsequent clinical outcomes trial and that could be implemented in clinical practice. We hypothesize that both arms will reduce nocturnal BP in comparison to "usual dosing". We further hypothesize that the "hs dosing" arm will raise daytime BP somewhat but have no net effect on 24 hour BP and that the "add on dosing" arm will have no effect on daytime BP but lower 24 hour BP.

This pilot study will begin after the last scheduled AASK Cohort study visit. Eligible participants will be treated for 6 weeks on each of 3 antihypertensive regimens. The sequence of the regimens will be random. Each period of the three periods will have 2 visits, one visit at 3 weeks and one visit at 6 weeks. In the last week of each 6-week period, a 24-hour ABPM will be obtained. The primary outcome variable is nocturnal BP; each pair wise difference between the regimens will be calculated.

Study Overview

• Status: Completed
• Conditions: Hypertensive Renal Disease
• Intervention / Treatment: Behavioral: USUAL - take your BP Meds as you usually do; Behavioral: HS DOSING; Drug: ADD On Dosing

• Study Type: Interventional
• Enrollment (Anticipated): 180
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California
    • Los Angeles, California, United States, 90059
      • Charles Drew Medical College
    • San Diego, California, United States, 92161
      • University of California at San Diego
  • Florida
    • Gainesville, Florida, United States, 32611
      • University of Florida
    • Miami, Florida, United States, 33101
      • University of Miami
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Emory University
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins University
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • University of Michigan
  • New York
    • New York, New York, United States, 10021
      • Lenox Hill Hospital
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals of Cleveland
    • Columbus, Ohio, United States, 43210
      • Ohio State University
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University
  • Texas
    • Dallas, Texas, United States, 75390
      • Univesity of Texas Southwestern Medical Center at Dallas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participant in the AASK Cohort Study
• Ability and willingness to provide informed consent
• Completion of a technically adequate ABPM at CO48 AASK cohort study visit.
• Participants must have had at least 2 visits in the last 12 months of the Cohort Study (July 1 2006 to June 1 2007)
• The average of last two BPs measured at least one week apart in the Cohort Study must be less than or equal to 140/90 mm Hg. This would exclude a small percentage of the AASK cohort population; however, it would enroll a group of participants with stable BP who should not require adjustments to their antihypertensive medications during the course of this study.
• Antihypertensive medications at baseline visit: This refers to the participant's antihypertensive regimen at the time of the baseline visit ; the transition period may be used to adjust the participant's antihypertensive regimen to meet these criteria, based on the clinical judgement of the site investigator.

Exclusion Criteria:

• Arm circumference greater than 50 cms.
• ESRD requiring renal replacement therapy or kidney transplantation
• Institutionalized participants
• Shift workers working at night
• MI or CVA within 3 months of AASK Cohort close out visit
• Participants with known ejection fraction less than 40%
• Females known to be pregnant or lactating
• Participants likely to reach end stage renal disease within the next six weeks, in the judgement of the site investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: USUAL; USUAL treatment - The patient's antihypertensive regimen at the baseline visit is the comparison (or control) regimen. All once a day medications will be administered in the morning.	Behavioral: USUAL - take your BP Meds as you usually do; The patient's antihypertensive regimen at the baseline visit is the comparison (or control) regimen. All once a day medications will be administered in the morning.
Experimental: HS Dosing; HS DOSING - In this period, the patient's antihypertensive regimen at the baseline visit will be standardized for the once/day medications to be given at bedtime.; For those on monotherapy with a once/day antihypertensive regimen, the time of administration will be changed to bed time.; For those on multi-drug therapy, the time of administration of all once a day antihypertensive drugs will be changed to bed time.	Behavioral: HS DOSING; Take your usual BP meds at bed time
Experimental: ADD-ON DOSING; ADD-ON DOSING - This regimen will start with the USUAL regimen to which an additional agent will be added at bed time. An additional dose of ramipril, diltiazem, or hydralazine are three possible options for the add on medication. The intent of the ADD ON therapy is to lower nocturnal BP with minimal impact on daytime BP. Thus, agents with < 24 hr duration of action are preferred. The specific choice and dose of add-on therapy (of the three agents) will be up to the site investigator considering the clinical situation of each participant based on the guidelines below.	Drug: ADD On Dosing; Take your usual BP meds but add one more med at bed time.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Night Time Blood Pressure	Night time blood pressure from APBM at weeks 6, 12, and 18

Secondary Outcome Measures

Outcome Measure	Time Frame
Blood pressure in the clinic Daytime blood pressure	Measured at weeks 6, 12, and 18

Collaborators and Investigators

• Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: George Bakris, MD, University of Chicago; Principal Investigator: Kenneth Jamerson, MD, University of Michigan; Principal Investigator: Lawrence Appel, MD, MPH, Johns Hopkins University; Study Chair: Mahboob Rahman, M.D., University Hospitals, Cleveland; Principal Investigator: Jackson T. Wright, Jr., MD, Ph.D., FACP, University Hospitals Cleveland Medical Center; Principal Investigator: Janice Lea, MD, Emory Center for Hypertension and Renal Disease Research; Principal Investigator: Francis B. Gabbai, MD, University of Calirfornia, San Diego; Principal Investigator: Otelio S. Randall, MD, Howard University; Principal Investigator: Keith Norris, MD, Charles Drew Medical Center; Principal Investigator: DeAnna Cheek, MD, Medical University of South Carolina; Principal Investigator: Michael Lipkowitz, MD, Lenox Hill Hospital; Principal Investigator: Lee Hebert, MD, Ohio State University; Principal Investigator: Stephen G. Rostand, MD, University of Alabama at Birmingham; Principal Investigator: Geraldine Bichier, MD, University of Florida; Principal Investigator: Gabriel Contreras, MD, University of Miami; Principal Investigator: Miroslav J. Smogorzewski, MD, University of Southern California; Principal Investigator: Robert D. Toto, MD, University of Texas, Southwestern Medical Center at Dallas; Principal Investigator: Julia A. Lewis, MD, Vanderbilt University

Publications and helpful links

General Publications

• Juraschek SP, Appel LJ, Miller ER 3rd. Metoprolol Increases Uric Acid and Risk of Gout in African Americans With Chronic Kidney Disease Attributed to Hypertension. Am J Hypertens. 2017 Sep 1;30(9):871-875. doi: 10.1093/ajh/hpx113.
• Rahman M, Greene T, Phillips RA, Agodoa LY, Bakris GL, Charleston J, Contreras G, Gabbai F, Hiremath L, Jamerson K, Kendrick C, Kusek JW, Lash JP, Lea J, Miller ER 3rd, Rostand S, Toto R, Wang X, Wright JT Jr, Appel LJ. A trial of 2 strategies to reduce nocturnal blood pressure in blacks with chronic kidney disease. Hypertension. 2013 Jan;61(1):82-8. doi: 10.1161/HYPERTENSIONAHA.112.200477. Epub 2012 Nov 19.

Study record dates

Study Major Dates

• Study Start: November 1, 2007
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: December 20, 2007
• First Submitted That Met QC Criteria: December 27, 2007
• First Posted (Estimate): December 28, 2007

Study Record Updates

• Last Update Posted (Estimate): April 16, 2012
• Last Update Submitted That Met QC Criteria: April 12, 2012
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Keywords: ABPM; African Americans; chronic renal disease; nocturnal blood pressure; hypertensive renal disease
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Urologic Diseases; Hypertension; Kidney Diseases
• Other Study ID Numbers: AASK ABPM Pilot (completed); 7 U01 KD04868