HypertensionPhase 4NCT00353652
Effects of Thiazide Diuretics on Sympathetic Nervous System in Hypertension
A Phase 4 study testing Study#1: chlorthalidone (CTD), titrated dose, Study #1: spironolactone (SP), titrated dose and Study# 2 chlorthalidone (CTD), fixed dose in people with Hypertension, run by University of Texas Southwestern Medical Center at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Hypertension
- What is being tested?
- Study#1: chlorthalidone (CTD), titrated dose, Study #1: spironolactone (SP), titrated dose and Study# 2 chlorthalidone (CTD), fixed dose
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 166 participants
- Where
- 2 sitesUnited States
- Study dates
- Jan 2005to Jan 2013
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Untreated stage 1 primary hypertension (systolic blood pressure between 140 to 159 mm Hg and diastolic blood pressure between 90 to 99 mm Hg)
Who cannot join
- 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)
Show all 10Show fewer
- History of gouty arthritis
- History of ACE inhibitor-induced cough or angioedema
- Evidence of secondary hypertension
- Pregnant
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, 75390
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
About this study
Official title: Neural Mechanisms of Thiazide-induced Insulin Resistance
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.
Read the detailed description
Thiazide medications, including chlorthalidone, are commonly prescribed for individuals with high blood pressure because they are inexpensive, effective at lowering blood pressure, and able to reduce the risk of heart failure and stroke. Despite these advantages, research has shown that thiazide medications may increase an individual's risk of developing diabetes. The exact mechanism that causes this remains unknown. Thiazide appears to increase sympathetic nervous system activity, thereby decreasing glucose reuptake and metabolism by skeletal muscle tissues. In turn, this tends to contribute to glucose intolerance and the development of diabetes. More research, however, is needed to confirm this link. Spironolactone, another blood pressure medication, does not pose the same risk for developing diabetes and may prove beneficial as a primary treatment for high blood pressure. The purpose of this study is to determine the role of the sympathetic nervous system in glucose metabolism in individuals with high blood pressure, as well as compare the effectiveness of thiazide, spironolactone, and other antihypertensive medications in reducing blood pressure. Results from this study may initiate the development of future clinical trials involving spironolactone as a primary treatment for reducing blood pressure.
This study will enroll individuals with high blood pressure. Study# 1: All subjects were randomized to receive 3 months chlorthalidone (12.5-25 mg/d) or spironolactone (50-75 mg/d), using a single-blind 2-phase crossover design without washout between treatments. Each subject was followed every 4 wk for measurement of 24-h ambulatory BP and serum potassium (K). The doses of chlorthalidone and spironolactone were titrated to achieve 24-h ambulatory BP of less than 130/80mmHg in the same subject. During chlorthalidone treatment period, subject was given oral K supplementation according to a sliding scale to maintain serum K from 4.0-4.5 mmol/liter. Then, sympathetic nerve activity (SNA) is measured after 3 months of chlorthalidone and after 3 months of spironolactone. Arterial baroreflex sensitivity, glucose, and insulin are measured at baseline, after 3 months of chlorthalidone, and after 3 months of spironolactone. Insulin sensitivity will be measured using HOMA-IR. Study #2: All subjects are randomized to 3 months of fixed-dose Chlorthalidone 25 mg once daily alone, fixed-dose Chlorthalidone 25 mg once daily plus fixed-dose Spironolactone 25 mg once daily, and fixed-dose Chlorthalidone 25 mg once daily plus fixed-dose Irbesartan 150 mg once daily, using a single-blind 3-phase crossover design without washout between treatments. Then, SNA , Arterial baroreflex sensitivity, glucose, and insulin are measured after 3 months of each treatment phase.
- Conditions
- Hypertension
- Being tested
- Study#1: chlorthalidone (CTD), titrated dose, Study #1: spironolactone (SP), titrated dose, Study# 2 chlorthalidone (CTD), fixed dose, Study# 2 spironolactone (SP), fixed dose, Study# 2 irbsesartan (IR), fixed dose
- Keywords
- Blood Pressure, High
- Medical subject headings
- Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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), 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# 2 chlorthalidone (CTD), fixed doseDrug
Participants in study #2 will receive 3 months of fixed-dose of CTD, at 25 mg/d.
Study# 2 spironolactone (SP), fixed doseDrug
Participants in study #2 will receive 3 months of fixed-dose SP at 25 mg daily.
Study# 2 irbsesartan (IR), fixed doseDrug
Participants in study #2 will receive 3 months of fixed-dose IR at150 mg daily.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Study#1: chlorthalidone (CTD), titrated dose; Drug: 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. Receives: Drug: Study#1: chlorthalidone (CTD), titrated dose; Drug: 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. Receives: Drug: Study# 2 chlorthalidone (CTD), fixed dose; Drug: Study# 2 spironolactone (SP), fixed dose; Drug: 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. Receives: Drug: Study# 2 chlorthalidone (CTD), fixed dose; Drug: Study# 2 spironolactone (SP), fixed dose; Drug: 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. Receives: Drug: Study# 2 chlorthalidone (CTD), fixed dose; Drug: Study# 2 spironolactone (SP), fixed dose; Drug: 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. Receives: Drug: Study# 2 chlorthalidone (CTD), fixed dose; Drug: Study# 2 spironolactone (SP), fixed dose; Drug: 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. Receives: Drug: Study# 2 chlorthalidone (CTD), fixed dose; Drug: Study# 2 spironolactone (SP), fixed dose; Drug: 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. Receives: Drug: Study# 2 chlorthalidone (CTD), fixed dose; Drug: Study# 2 spironolactone (SP), fixed dose; Drug: Study# 2 irbsesartan (IR), fixed dose |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sympathetic Nerve Activity
Measured: Measured at 3 months
Secondary outcomes (4)
24-hour Ambulatory Systolic Blood Pressure
Measured: Measured at 3 months
Insulin
fasting plasma insulin
Measured: 3 months
HOMA-IR
assessment of insulin resistance calculated by multiplying fasting plasma insulin (mU/l) with fasting plasma glucose (mmol/l) divided by 22.5.
Measured: 3 months
Sympathetic Baroreflex Sensitivity
slope relating percent change in SNA (% change in total activity from baseline) to diastolic BP.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jul 2006 (estimated)
- Study startJan 2005
- Primary completionJan 2013
- Study completionJan 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for HypertensionStudies of the same condition, open and under way.
- More trials run by University of Texas Southwestern Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 166 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Texas Southwestern Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Wanpen Vongpatanasin, University of Texas Southwestern Medical Center
- Investigators
- Wanpen Vongpatanasin, MD, Principal investigator, University of Texas, Southwestern Medical Center at Dallas
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00353652
- Sponsor's protocol ID
- 413
- Other IDs
- R01HL078782-02
- Status last verified
- Feb 2019
- First submitted
- 18 Jul 2006
- Last updated
- 6 Feb 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 22733474Kontak 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.
PubMed 20660053
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neural Mechanisms of Thiazide-induced Insulin Resistance
- ClinicalTrials.gov ID
- NCT00353652
- Acronym / sponsor ID
- 413
- Conditions
- Hypertension
- Keywords
- Blood Pressure, High
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 166 participants (actual)
- Lead sponsor
- University of Texas Southwestern Medical CenterUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Jan 2005
- Primary completion
- Jan 2013 (actual)
- Study completion
- Jan 2013 (actual)
- First posted
- 19 Jul 2006 (estimated)
- Results
- Posted 29 Dec 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Thiazide medications, including chlorthalidone, are commonly prescribed for individuals with high blood pressure because they are inexpensive, effective at lowering blood pressure, and able to reduce the risk of heart failure and stroke. Despite these advantages, research has shown that thiazide medications may increase an individual's risk of developing diabetes. The exact mechanism that causes this remains unknown. Thiazide appears to increase sympathetic nervous system activity, thereby decreasing glucose reuptake and metabolism by skeletal muscle tissues. In turn, this tends to contribute to glucose intolerance and the development of diabetes. More research, however, is needed to confirm this link. Spironolactone, another blood pressure medication, does not pose the same risk for developing diabetes and may prove beneficial as a primary treatment for high blood pressure. The purpose of this study is to determine the role of the sympathetic nervous system in glucose metabolism in individuals with high blood pressure, as well as compare the effectiveness of thiazide, spironolactone, and other antihypertensive medications in reducing blood pressure. Results from this study may initiate the development of future clinical trials involving spironolactone as a primary treatment for reducing blood pressure.
This study will enroll individuals with high blood pressure. Study# 1: All subjects were randomized to receive 3 months chlorthalidone (12.5-25 mg/d) or spironolactone (50-75 mg/d), using a single-blind 2-phase crossover design without washout between treatments. Each subject was followed every 4 wk for measurement of 24-h ambulatory BP and serum potassium (K). The doses of chlorthalidone and spironolactone were titrated to achieve 24-h ambulatory BP of less than 130/80mmHg in the same subject. During chlorthalidone treatment period, subject was given oral K supplementation according to a sliding scale to maintain serum K from 4.0-4.5 mmol/liter. Then, sympathetic nerve activity (SNA) is measured after 3 months of chlorthalidone and after 3 months of spironolactone. Arterial baroreflex sensitivity, glucose, and insulin are measured at baseline, after 3 months of chlorthalidone, and after 3 months of spironolactone. Insulin sensitivity will be measured using HOMA-IR. Study #2: All subjects are randomized to 3 months of fixed-dose Chlorthalidone 25 mg once daily alone, fixed-dose Chlorthalidone 25 mg once daily plus fixed-dose Spironolactone 25 mg once daily, and fixed-dose Chlorthalidone 25 mg once daily plus fixed-dose Irbesartan 150 mg once daily, using a single-blind 3-phase crossover design without washout between treatments. Then, SNA , Arterial baroreflex sensitivity, glucose, and insulin are measured after 3 months of each treatment phase.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Study#1: chlorthalidone (CTD) first then spironolactone (SP) | Active comparator | Drug: Study#1: chlorthalidone (CTD), titrated dose, Drug: Study #1: spironolactone (SP), titrated doseParticipants 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. |
| Study #1: spironolactone (SP) first, then chlorthalidone (CTD) | Active comparator | Drug: Study#1: chlorthalidone (CTD), titrated dose, Drug: Study #1: spironolactone (SP), titrated doseParticipants 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. |
| Study# 2 CTD alone 1st, CTD+ SP 2nd, CTD+IR 3rd | Active comparator | Drug: Study# 2 chlorthalidone (CTD), fixed dose, Drug: Study# 2 spironolactone (SP), fixed dose, Drug: Study# 2 irbsesartan (IR), fixed doseSubjects 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. |
| Study# 2 CTD alone 1st, CTD+IR 2nd, CTD+SP3rd | Active comparator | Drug: Study# 2 chlorthalidone (CTD), fixed dose, Drug: Study# 2 spironolactone (SP), fixed dose, Drug: Study# 2 irbsesartan (IR), fixed doseSubjects 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. |
| Study# 2 CTD+SP1st, CTD alone 2nd, CTD+IR 3rd | Active comparator | Drug: Study# 2 chlorthalidone (CTD), fixed dose, Drug: Study# 2 spironolactone (SP), fixed dose, Drug: Study# 2 irbsesartan (IR), fixed doseSubjects 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. |
| Study# 2 CTD+SP1st, CTD+IR 2nd, CTD alone 3rd | Active comparator | Drug: Study# 2 chlorthalidone (CTD), fixed dose, Drug: Study# 2 spironolactone (SP), fixed dose, Drug: Study# 2 irbsesartan (IR), fixed doseSubjects 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. |
| Study# 2 CTD+IR 1st, CTD alone 2nd, CTD+SP 3rd | Active comparator | Drug: Study# 2 chlorthalidone (CTD), fixed dose, Drug: Study# 2 spironolactone (SP), fixed dose, Drug: Study# 2 irbsesartan (IR), fixed doseSubjects 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. |
| Study# 2 CTD+IR 1st, CTD+SP 2nd, CTD alone 3rd | Active comparator | Drug: Study# 2 chlorthalidone (CTD), fixed dose, Drug: Study# 2 spironolactone (SP), fixed dose, Drug: Study# 2 irbsesartan (IR), fixed doseSubjects 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Untreated stage 1 primary hypertension (systolic blood pressure between 140 to 159 mm Hg and diastolic blood pressure between 90 to 99 mm Hg)
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Study#1: chlorthalidone (CTD), titrated doseParticipants 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 | Drug | Study #1: spironolactone (SP) first, then chlorthalidone (CTD), Study#1: chlorthalidone (CTD) first then spironolactone (SP) |
| Study #1: spironolactone (SP), titrated doseParticipants 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. | Drug | Study #1: spironolactone (SP) first, then chlorthalidone (CTD), Study#1: chlorthalidone (CTD) first then spironolactone (SP) |
| Study# 2 chlorthalidone (CTD), fixed doseParticipants in study #2 will receive 3 months of fixed-dose of CTD, at 25 mg/d. | Drug | Study# 2 CTD alone 1st, CTD+ SP 2nd, CTD+IR 3rd, Study# 2 CTD alone 1st, CTD+IR 2nd, CTD+SP3rd, Study# 2 CTD+IR 1st, CTD alone 2nd, CTD+SP 3rd, Study# 2 CTD+IR 1st, CTD+SP 2nd, CTD alone 3rd, Study# 2 CTD+SP1st, CTD alone 2nd, CTD+IR 3rd, Study# 2 CTD+SP1st, CTD+IR 2nd, CTD alone 3rd |
| Study# 2 spironolactone (SP), fixed doseParticipants in study #2 will receive 3 months of fixed-dose SP at 25 mg daily. | Drug | Study# 2 CTD alone 1st, CTD+ SP 2nd, CTD+IR 3rd, Study# 2 CTD alone 1st, CTD+IR 2nd, CTD+SP3rd, Study# 2 CTD+IR 1st, CTD alone 2nd, CTD+SP 3rd, Study# 2 CTD+IR 1st, CTD+SP 2nd, CTD alone 3rd, Study# 2 CTD+SP1st, CTD alone 2nd, CTD+IR 3rd, Study# 2 CTD+SP1st, CTD+IR 2nd, CTD alone 3rd |
| Study# 2 irbsesartan (IR), fixed doseParticipants in study #2 will receive 3 months of fixed-dose IR at150 mg daily. | Drug | Study# 2 CTD alone 1st, CTD+ SP 2nd, CTD+IR 3rd, Study# 2 CTD alone 1st, CTD+IR 2nd, CTD+SP3rd, Study# 2 CTD+IR 1st, CTD alone 2nd, CTD+SP 3rd, Study# 2 CTD+IR 1st, CTD+SP 2nd, CTD alone 3rd, Study# 2 CTD+SP1st, CTD alone 2nd, CTD+IR 3rd, Study# 2 CTD+SP1st, CTD+IR 2nd, CTD alone 3rd |
Primary outcome
Sympathetic Nerve Activity
Time frame: Measured at 3 months
4 secondary outcomes
24-hour Ambulatory Systolic Blood Pressure
Time frame: Measured at 3 months
Insulin
Time frame: 3 months
HOMA-IR
Time frame: 3 months
Sympathetic Baroreflex Sensitivity
Time frame: 3 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 22733474Raheja 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.
- Derived from this study: PubMed 20660053Kontak 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.
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Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
Recruiting
Trial Phase: Syndemic Adapted Medly Uganda
Mental Health
Not yet recruitingPhase 2/3
An Open-Label Extension Study to Evaluate Inhaled Treprostinil SMI in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Enrolling by invitation
Testing Implementation Strategies to Support Clinic Fidelity to an Outpatient Hypertension Bundle
Pregnancy Related, Hypertension
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Wanpen Vongpatanasin, MD principal investigator
University of Texas, Southwestern Medical Center at Dallas
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Study#1: chlorthalidone (CTD), titrated dose, Study #1: spironolactone (SP), titrated dose and Study# 2 chlorthalidone (CTD), fixed dose in people with Hypertension, run by University of Texas Southwestern Medical Center at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Dec 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Sympathetic Nerve Activity (time frame: Measured at 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00353652, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2019.