NCT00353652

Brief Summary

Thiazide medications are often prescribed for individuals with high blood pressure, but research has shown that they may increase an individual's risk of developing diabetes. While it is unknown exactly how thiazide causes this response, it is likely that the nervous system is somehow involved. This study will evaluate the role of the nervous system in sugar metabolism, as well as determine the effect of thiazide and other medications on individuals with high blood pressure.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
166

participants targeted

Target at P50-P75 for phase_4 hypertension

Timeline
Completed

Started Jan 2005

Longer than P75 for phase_4 hypertension

Geographic Reach
1 country

2 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

January 1, 2005

Completed
1.5 years until next milestone

First Submitted

Initial submission to the registry

July 18, 2006

Completed
1 day until next milestone

First Posted

Study publicly available on registry

July 19, 2006

Completed
6.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2013

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2013

Completed
2 years until next milestone

Results Posted

Study results publicly available

December 29, 2014

Completed
Last Updated

February 6, 2019

Status Verified

February 1, 2019

Enrollment Period

8 years

First QC Date

July 18, 2006

Results QC Date

December 2, 2014

Last Update Submit

February 1, 2019

Conditions

Hypertension

Keywords

Blood Pressure, High

Outcome Measures

Primary Outcomes (1)

  • Sympathetic Nerve Activity

    Measured at 3 months

Secondary Outcomes (4)

  • 24-hour Ambulatory Systolic Blood Pressure

    Measured at 3 months

  • Insulin

    3 months

  • HOMA-IR

    3 months

  • Sympathetic Baroreflex Sensitivity

    3 months

Study Arms (8)

Study#1: chlorthalidone (CTD) first then spironolactone (SP)

ACTIVE COMPARATOR

Participants in study #1 only received 2 interventions. All subjects are randomized to receive 3 months of chlorthalidone first (12.5-25 mg/d), using a single-blind 2-phase crossover design. Then, the subject is transitioned to treatment with spironolactone (25-75 mg/d)without washout period for 3 months. Following 3 month treatment period, the procedures listed below were performed. After completion of the study procedures, the medication is discontinued.

Drug: Study#1: chlorthalidone (CTD), titrated doseDrug: Study #1: spironolactone (SP), titrated dose

Study #1: spironolactone (SP) first, then chlorthalidone (CTD)

ACTIVE COMPARATOR

Participants in study #1 only received 2 interventions. All subjects are randomized to receive 3 months spironolactone first (25-75 mg/d), using a single-blind 2-phase crossover design. Then, the subject is transitioned to treatment with chlorthalidone(12.5-25 mg/d) without washout period. Following 3 month treatment period, the procedures listed below were performed. After completion of the study procedures, the medication is discontinued.

Drug: Study#1: chlorthalidone (CTD), titrated doseDrug: Study #1: spironolactone (SP), titrated dose

Study# 2 CTD alone 1st, CTD+ SP 2nd, CTD+IR 3rd

ACTIVE COMPARATOR

Subjects are randomized to receive 3 months of fixed-dose chlorthalidone (CTD, 25 mg/d) alone first, using a single-blind 3-phase crossover design. Then, subjects are treated with fixed-dose CTD (25 mg/d) plus fixed-dosespironolactone (SP) 25 mg daily for 3 months, then fixed-dose CTD (25 mg/d) plus fixed-dose irbsesartan (IR, 150 mg daily) for 3 months. After completion of the study procedures, the medication is discontinued.

Drug: Study# 2 chlorthalidone (CTD), fixed doseDrug: Study# 2 spironolactone (SP), fixed doseDrug: Study# 2 irbsesartan (IR), fixed dose

Study# 2 CTD alone 1st, CTD+IR 2nd, CTD+SP3rd

ACTIVE COMPARATOR

Subjects are randomized to receive 3 months of fixed-dose chlorthalidone (CTD, 25 mg/d) alone first, using a single-blind 3-phase crossover design. Then, subjects are treated with fixed-dose CTD 25 mg/d plus fixed-dose irbsesartan (IR, 150 mg daily) for 3 months, followed by fixed-dose CTD (25 mg/d) plus fixed-dose spironolactone (SP) 25 mg daily for 3 months. After completion of the study procedures, the medication is discontinued.

Drug: Study# 2 chlorthalidone (CTD), fixed doseDrug: Study# 2 spironolactone (SP), fixed doseDrug: Study# 2 irbsesartan (IR), fixed dose

Study# 2 CTD+SP1st, CTD alone 2nd, CTD+IR 3rd

ACTIVE COMPARATOR

Subjects are randomized to receive fixed-dose CTD (25 mg/d) plus fixed-dose spironolactone (SP) 25 mg daily for 3 months, using a single-blind 3-phase crossover design. Then, subjects are treated with fixed-dose CTD 25 mg/d alone for 3 months, then fixed-dose CTD 25 mg/d plus fixed-dose irbsesartan (IR, 150 mg daily) for 3 months. After completion of the study procedures, the medication is discontinued.

Drug: Study# 2 chlorthalidone (CTD), fixed doseDrug: Study# 2 spironolactone (SP), fixed doseDrug: Study# 2 irbsesartan (IR), fixed dose

Study# 2 CTD+SP1st, CTD+IR 2nd, CTD alone 3rd

ACTIVE COMPARATOR

Subjects are randomized to receive fixed-dose CTD (25 mg/d) plus fixed-dose spironolactone (SP) 25 mg daily for 3 months, using a single-blind 3-phase crossover design. Then, subjects are treated with fixed-dose CTD 25 mg/d plus fixed-dose irbsesartan (IR, 150 mg daily) for 3 months, then fixed-dose CTD 25 mg/d alone for 3 months. After completion of the study procedures, the medication is discontinued.

Drug: Study# 2 chlorthalidone (CTD), fixed doseDrug: Study# 2 spironolactone (SP), fixed doseDrug: Study# 2 irbsesartan (IR), fixed dose

Study# 2 CTD+IR 1st, CTD alone 2nd, CTD+SP 3rd

ACTIVE COMPARATOR

Subjects are randomized to receive fixed-dose CTD 25 mg/d plus fixed-dose irbsesartan (IR, 150 mg daily) for 3 months, using a single-blind 3-phase crossover design. Then, subjects are treated with fixed-dose CTD 25 mg/d alone for 3 months, then fixed-dose CTD (25 mg/d) plus fixed-dose spironolactone (SP) 25 mg daily for 3 months. After completion of the study procedures, the medication is discontinued.

Drug: Study# 2 chlorthalidone (CTD), fixed doseDrug: Study# 2 spironolactone (SP), fixed doseDrug: Study# 2 irbsesartan (IR), fixed dose

Study# 2 CTD+IR 1st, CTD+SP 2nd, CTD alone 3rd

ACTIVE COMPARATOR

Subjects are randomized to receive fixed-dose CTD 25 mg/d plus fixed-dose irbsesartan (IR, 150 mg daily) for 3 months, using a single-blind 3-phase crossover design. Then, subjects are treated with fixed-dose CTD (25 mg/d) plus fixed-dose spironolactone (SP) 25 mg daily for 3 months, followed by fixed-dose CTD 25 mg/d alone for 3 months. After completion of the study procedures, the medication is discontinued.

Drug: Study# 2 chlorthalidone (CTD), fixed doseDrug: Study# 2 spironolactone (SP), fixed doseDrug: Study# 2 irbsesartan (IR), fixed dose

Interventions

Study#1: chlorthalidone (CTD), titrated doseDRUG

Participants in study #1 will receive 3 months of chlorthalidone (12.5-25 mg/d) at the dose titrated to achieve 24-h ambulatory BP \< 130/80 mmHg

Study #1: spironolactone (SP) first, then chlorthalidone (CTD)Study#1: chlorthalidone (CTD) first then spironolactone (SP)
Study #1: spironolactone (SP), titrated doseDRUG

Participants in study #1 will receive 3 months spironolactone (25-75 mg/d), at the dose titrated to achieve 24-h ambulatory BP \< 130/80 mmHg.

Study #1: spironolactone (SP) first, then chlorthalidone (CTD)Study#1: chlorthalidone (CTD) first then spironolactone (SP)
Study# 2 chlorthalidone (CTD), fixed doseDRUG

Participants in study #2 will receive 3 months of fixed-dose of CTD, at 25 mg/d.

Study# 2 CTD alone 1st, CTD+ SP 2nd, CTD+IR 3rdStudy# 2 CTD alone 1st, CTD+IR 2nd, CTD+SP3rdStudy# 2 CTD+IR 1st, CTD alone 2nd, CTD+SP 3rdStudy# 2 CTD+IR 1st, CTD+SP 2nd, CTD alone 3rdStudy# 2 CTD+SP1st, CTD alone 2nd, CTD+IR 3rdStudy# 2 CTD+SP1st, CTD+IR 2nd, CTD alone 3rd
Study# 2 spironolactone (SP), fixed doseDRUG

Participants in study #2 will receive 3 months of fixed-dose SP at 25 mg daily.

Study# 2 CTD alone 1st, CTD+ SP 2nd, CTD+IR 3rdStudy# 2 CTD alone 1st, CTD+IR 2nd, CTD+SP3rdStudy# 2 CTD+IR 1st, CTD alone 2nd, CTD+SP 3rdStudy# 2 CTD+IR 1st, CTD+SP 2nd, CTD alone 3rdStudy# 2 CTD+SP1st, CTD alone 2nd, CTD+IR 3rdStudy# 2 CTD+SP1st, CTD+IR 2nd, CTD alone 3rd
Study# 2 irbsesartan (IR), fixed doseDRUG

Participants in study #2 will receive 3 months of fixed-dose IR at150 mg daily.

Study# 2 CTD alone 1st, CTD+ SP 2nd, CTD+IR 3rdStudy# 2 CTD alone 1st, CTD+IR 2nd, CTD+SP3rdStudy# 2 CTD+IR 1st, CTD alone 2nd, CTD+SP 3rdStudy# 2 CTD+IR 1st, CTD+SP 2nd, CTD alone 3rdStudy# 2 CTD+SP1st, CTD alone 2nd, CTD+IR 3rdStudy# 2 CTD+SP1st, CTD+IR 2nd, CTD alone 3rd

Eligibility Criteria

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

You may qualify if:

  • Untreated stage 1 primary hypertension (systolic blood pressure between 140 to 159 mm Hg and diastolic blood pressure between 90 to 99 mm Hg)

You may not qualify if:

  • Cardiopulmonary disease, as determined by medical history or by physical examination
  • Serum creatinine greater than or equal to 1.5 mg/dL
  • Diabetes mellitus or other systemic illness
  • Left ventricular hypertrophy by echocardiography or ECG
  • Hypersensitivity to chlorthalidone, spironolactone, eplerenone, angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blocker, insulin, Evans blue dye, or clonidine
  • History of substance abuse (other than tobacco)
  • History of gouty arthritis
  • History of ACE inhibitor-induced cough or angioedema
  • Evidence of secondary hypertension
  • Pregnant

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, 75390, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Related Publications (2)

  • Raheja P, Price A, Wang Z, Arbique D, Adams-Huet B, Auchus RJ, Vongpatanasin W. Spironolactone prevents chlorthalidone-induced sympathetic activation and insulin resistance in hypertensive patients. Hypertension. 2012 Aug;60(2):319-25. doi: 10.1161/HYPERTENSIONAHA.112.194787. Epub 2012 Jun 25.

    PMID: 22733474DERIVED

  • Kontak AC, Wang Z, Arbique D, Adams-Huet B, Auchus RJ, Nesbitt SD, Victor RG, Vongpatanasin W. Reversible sympathetic overactivity in hypertensive patients with primary aldosteronism. J Clin Endocrinol Metab. 2010 Oct;95(10):4756-61. doi: 10.1210/jc.2010-0823. Epub 2010 Jul 21.

    PMID: 20660053DERIVED

MeSH Terms

Conditions

Hypertension

Condition Hierarchy (Ancestors)

Vascular DiseasesCardiovascular Diseases

Results Point of Contact

Title
Wanpen Vongpatanasin
Organization
University of Texas Southwestern Medical Center
wanpen.vongpatanasin@utsouthwestern.edu
2146458000

Study Officials

  • Wanpen Vongpatanasin, MD

    University of Texas, Southwestern Medical Center at Dallas

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
PARTICIPANT
Masking Details
Capsule was made to appear identical in appearance so that subjects are blinded to treatment assigned.
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
M.D.

Study Record Dates

First Submitted

July 18, 2006

First Posted

July 19, 2006

Study Start

January 1, 2005

Primary Completion

January 1, 2013

Study Completion

January 1, 2013

Last Updated

February 6, 2019

Results First Posted

December 29, 2014

Record last verified: 2019-02

Locations

US(2)