NCT01203852

Brief Summary

There are many medications available for the treatment of high blood pressure (hypertension), but finding the right one for a specific patient can be challenging. In fact, it is estimated that less than 50% of people with hypertension have their blood pressure under control. The hypothesis is that genetic differences between individuals influence their response to antihypertensive medications. This study is aimed at determining the genetic factors that may influence a person's response to either a beta-blocker or a thiazide diuretic. The hope is that through this research, the investigators may someday be able to use an individual's genetic information to guide the selection of their blood pressure medicine, leading to better control of blood pressure, and less need for the current trial and error process.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
839

participants targeted

Target at P75+ for phase_4 hypertension

Timeline
Completed

Started Aug 2010

Longer than P75 for phase_4 hypertension

Geographic Reach
1 country

3 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

August 1, 2010

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

September 15, 2010

Completed
1 day until next milestone

First Posted

Study publicly available on registry

September 16, 2010

Completed
3.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2014

Completed
1.1 years until next milestone

Results Posted

Study results publicly available

May 19, 2015

Completed
Last Updated

April 6, 2018

Status Verified

April 1, 2018

Enrollment Period

3.7 years

First QC Date

September 15, 2010

Results QC Date

April 29, 2015

Last Update Submit

April 4, 2018

Conditions

Hypertension

Keywords

hypertensionantihypertensive drugpharmacogeneticsgeneticsblood pressureglucose

Outcome Measures

Primary Outcomes (1)

  • Change in Blood Pressure From Baseline to Treatment

    Response to blood pressure medication will be assessed by measuring blood pressure before and after treatment

    after 6-8 weeks of treatment

Secondary Outcomes (1)

  • Adverse Metabolic Effects

    after 6-8 weeks treatment

Study Arms (1)

Metoprolol + Chlorthalidone

EXPERIMENTAL

Study participants in this group had their current hypertension treatment withdrawn, baseline labs drawn and hypertension documented. Participants were initiated on metoprolol tartrate 50 mg twice daily for two weeks, followed by dose titration to 100 mg twice daily for six additional weeks if blood pressure (BP) \> 120/70 mmHg. BP measures were again recorded. Participants entered a washout where metoprolol was titrated, then discontinued, and the patient's hypertension was re-established. After another set of identical baseline labs, study participants were initiated on chlorthalidone 25 mg four days per week (Monday, Wednesday, Thursday, Saturday) 15 mg daily for two weeks, followed by 25 mg daily for an additional six weeks.

Drug: MetoprololDrug: Chlorthalidone

Interventions

MetoprololDRUG

Metoprolol 50 mg twice daily titrated to 100 mg twice daily Note: due to discontinuation of the manufacture of chlorthalidone 15 mg, effective Jan 1, 2013; the starting dose of chlorthalidone will be 25 mg 4 times per week (Mon, Wed, Thur, Sat) with subsequent titration to 25 mg daily.

Also known as: Lopressor, Toprol XL
Metoprolol + Chlorthalidone
ChlorthalidoneDRUG

Chlorthalidone 25 mg 4 times per week titrated to 25 mg daily

Also known as: Thalitone
Metoprolol + Chlorthalidone

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • An average seated home diastolic blood pressure (DBP) \> 85 mmHg and \< 110 mmHg and home systolic blood pressure (SBP) \< 180 mmHg.
  • Subjects must also have an average seated (\> 5 minutes) clinic DBP between 90 mmHg and 110 mmHg and SBP \< 180 mmHg

You may not qualify if:

  • Secondary forms of hypertension (HTN) (including sleep apnea)
  • Isolated systolic HTN
  • Other diseases requiring treatment with BP lowering medications
  • Heart rate \< 55 beats/min (for metoprolol only)
  • Known cardiovascular disease (including history of angina pectoris, heart failure, presence of a cardiac pacemaker, history of myocardial infarction or revascularization procedure, or cerebrovascular disease, including stroke and TIA)
  • Diabetes mellitus (Type 1 or 2)
  • Renal insufficiency (serum creatinine \> 1.5 in men or 1.4 in women)
  • Primary renal disease
  • Pregnancy or lactation
  • Liver enzymes \> 2.5 upper limits of normal
  • Current treatment with NSAIDS, cyclooxygenase-2 (COX2) inhibitors, oral contraceptives or estrogen.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

University of Florida

Gainesville, Florida, 32610, United States

Location

Emory University School of Medicine

Atlanta, Georgia, 30322, United States

Location

Mayo Clinic, Division of Hypertension

Rochester, Minnesota, 55905, United States

Location

Related Publications (7)

  • Hamadeh IS, Langaee TY, Dwivedi R, Garcia S, Burkley BM, Skaar TC, Chapman AB, Gums JG, Turner ST, Gong Y, Cooper-DeHoff RM, Johnson JA. Impact of CYP2D6 polymorphisms on clinical efficacy and tolerability of metoprolol tartrate. Clin Pharmacol Ther. 2014 Aug;96(2):175-81. doi: 10.1038/clpt.2014.62. Epub 2014 Mar 17.

    PMID: 24637943BACKGROUND

  • Mehanna M, McDonough CW, Smith SM, Gong Y, Gums JG, Chapman AB, Johnson JA, Cooper-DeHoff RM. Integrated metabolomics analysis reveals mechanistic insights into variability in blood pressure response to thiazide diuretics and beta blockers. Clin Transl Sci. 2024 May;17(5):e13816. doi: 10.1111/cts.13816.

    PMID: 38747311DERIVED

  • Chekka LMS, Tantawy M, Langaee T, Wang D, Renne R, Chapman AB, Gums JG, Boerwinkle E, Cooper-DeHoff RM, Johnson JA. Circulating microRNA Biomarkers of Thiazide Response in Hypertension. J Am Heart Assoc. 2024 Feb 20;13(4):e032433. doi: 10.1161/JAHA.123.032433. Epub 2024 Feb 14.

    PMID: 38353215DERIVED

  • Mehanna M, Wang Z, Gong Y, McDonough CW, Beitelshees AL, Gums JG, Chapman AB, Schwartz GL, Bailey KR, Johnson JA, Turner ST, Cooper-DeHoff RM. Plasma Renin Activity Is a Predictive Biomarker of Blood Pressure Response in European but not in African Americans With Uncomplicated Hypertension. Am J Hypertens. 2019 Jun 11;32(7):668-675. doi: 10.1093/ajh/hpz022.

    PMID: 30753254DERIVED

  • Sa ACC, Webb A, Gong Y, McDonough CW, Shahin MH, Datta S, Langaee TY, Turner ST, Beitelshees AL, Chapman AB, Boerwinkle E, Gums JG, Scherer SE, Cooper-DeHoff RM, Sadee W, Johnson JA. Blood pressure signature genes and blood pressure response to thiazide diuretics: results from the PEAR and PEAR-2 studies. BMC Med Genomics. 2018 Jun 20;11(1):55. doi: 10.1186/s12920-018-0370-x.

    PMID: 29925376DERIVED

  • Singh S, McDonough CW, Gong Y, Alghamdi WA, Arwood MJ, Bargal SA, Dumeny L, Li WY, Mehanna M, Stockard B, Yang G, de Oliveira FA, Fredette NC, Shahin MH, Bailey KR, Beitelshees AL, Boerwinkle E, Chapman AB, Gums JG, Turner ST, Cooper-DeHoff RM, Johnson JA. Genome Wide Association Study Identifies the HMGCS2 Locus to be Associated With Chlorthalidone Induced Glucose Increase in Hypertensive Patients. J Am Heart Assoc. 2018 Mar 9;7(6):e007339. doi: 10.1161/JAHA.117.007339.

    PMID: 29523524DERIVED

  • Shahin MH, Sa AC, Webb A, Gong Y, Langaee T, McDonough CW, Riva A, Beitleshees AL, Chapman AB, Gums JG, Turner ST, Boerwinkle E, Scherer SE, Sadee W, Cooper-DeHoff RM, Johnson JA. Genome-Wide Prioritization and Transcriptomics Reveal Novel Signatures Associated With Thiazide Diuretics Blood Pressure Response. Circ Cardiovasc Genet. 2017 Jan;10(1):e001404. doi: 10.1161/CIRCGENETICS.116.001404.

    PMID: 28115488DERIVED

Related Links

MeSH Terms

Conditions

Hypertension

Interventions

MetoprololChlorthalidone

Condition Hierarchy (Ancestors)

Vascular DiseasesCardiovascular Diseases

Intervention Hierarchy (Ancestors)

PhenoxypropanolaminesPropanolaminesAmino AlcoholsAlcoholsOrganic ChemicalsPropanolsAminesBenzenesulfonamidesSulfonamidesAmidesBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsBenzophenonesPhthalimidesImidesKetonesSulfonesSulfur CompoundsIsoindolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Results Point of Contact

Title
Dr. Julie A. Johnson
Organization
University of Florida
johnson@cop.ufl.edu
(352) 273-6309

Study Officials

  • Julie A Johnson, PharmD

    University of Florida

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 4
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 15, 2010

First Posted

September 16, 2010

Study Start

August 1, 2010

Primary Completion

April 1, 2014

Study Completion

April 1, 2014

Last Updated

April 6, 2018

Results First Posted

May 19, 2015

Record last verified: 2018-04

Locations

US(3)