Effects of Thiazide Diuretics on Sympathetic Nervous System in Hypertension
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
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
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Study#1: chlorthalidone (CTD) first then spironolactone (SP) 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 dose
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
Drug: Study #1: spironolactone (SP), titrated dose
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.
|
| Active Comparator: Study #1: spironolactone (SP) first, then chlorthalidone (CTD) 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 dose
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
Drug: Study #1: spironolactone (SP), titrated dose
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.
|
| Active Comparator: Study# 2 CTD alone 1st, CTD+ SP 2nd, CTD+IR 3rd 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 dose
Participants in study #2 will receive 3 months of fixed-dose of CTD, at 25 mg/d.
Drug: Study# 2 spironolactone (SP), fixed dose
Participants in study #2 will receive 3 months of fixed-dose SP at 25 mg daily.
Drug: Study# 2 irbsesartan (IR), fixed dose
Participants in study #2 will receive 3 months of fixed-dose IR at150 mg daily.
|
| Active Comparator: Study# 2 CTD alone 1st, CTD+IR 2nd, CTD+SP3rd 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 dose
Participants in study #2 will receive 3 months of fixed-dose of CTD, at 25 mg/d.
Drug: Study# 2 spironolactone (SP), fixed dose
Participants in study #2 will receive 3 months of fixed-dose SP at 25 mg daily.
Drug: Study# 2 irbsesartan (IR), fixed dose
Participants in study #2 will receive 3 months of fixed-dose IR at150 mg daily.
|
| Active Comparator: Study# 2 CTD+SP1st, CTD alone 2nd, CTD+IR 3rd 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 dose
Participants in study #2 will receive 3 months of fixed-dose of CTD, at 25 mg/d.
Drug: Study# 2 spironolactone (SP), fixed dose
Participants in study #2 will receive 3 months of fixed-dose SP at 25 mg daily.
Drug: Study# 2 irbsesartan (IR), fixed dose
Participants in study #2 will receive 3 months of fixed-dose IR at150 mg daily.
|
| Active Comparator: Study# 2 CTD+SP1st, CTD+IR 2nd, CTD alone 3rd 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 dose
Participants in study #2 will receive 3 months of fixed-dose of CTD, at 25 mg/d.
Drug: Study# 2 spironolactone (SP), fixed dose
Participants in study #2 will receive 3 months of fixed-dose SP at 25 mg daily.
Drug: Study# 2 irbsesartan (IR), fixed dose
Participants in study #2 will receive 3 months of fixed-dose IR at150 mg daily.
|
| Active Comparator: Study# 2 CTD+IR 1st, CTD alone 2nd, CTD+SP 3rd 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 dose
Participants in study #2 will receive 3 months of fixed-dose of CTD, at 25 mg/d.
Drug: Study# 2 spironolactone (SP), fixed dose
Participants in study #2 will receive 3 months of fixed-dose SP at 25 mg daily.
Drug: Study# 2 irbsesartan (IR), fixed dose
Participants in study #2 will receive 3 months of fixed-dose IR at150 mg daily.
|
| Active Comparator: Study# 2 CTD+IR 1st, CTD+SP 2nd, CTD alone 3rd 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 dose
Participants in study #2 will receive 3 months of fixed-dose of CTD, at 25 mg/d.
Drug: Study# 2 spironolactone (SP), fixed dose
Participants in study #2 will receive 3 months of fixed-dose SP at 25 mg daily.
Drug: Study# 2 irbsesartan (IR), fixed dose
Participants in study #2 will receive 3 months of fixed-dose IR at150 mg daily.
|
Outcome Measures
Primary Outcome Measures
- Sympathetic Nerve Activity [Measured at 3 months]
Secondary Outcome Measures
- 24-hour Ambulatory Systolic Blood Pressure [Measured at 3 months]
- Insulin [3 months]
fasting plasma insulin
- HOMA-IR [3 months]
assessment of insulin resistance calculated by multiplying fasting plasma insulin (mU/l) with fasting plasma glucose (mmol/l) divided by 22.5.
- Sympathetic Baroreflex Sensitivity [3 months]
slope relating percent change in SNA (% change in total activity from baseline) to diastolic BP.
Eligibility Criteria
Criteria
Inclusion Criteria:
- Untreated stage 1 primary hypertension (systolic blood pressure between 140 to 159 mm Hg and diastolic blood pressure between 90 to 99 mm Hg)
Exclusion Criteria:
-
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Texas Southwestern Medical Center at Dallas | Dallas | Texas | United States | 75390 |
| 2 | University of Texas Southwestern Medical Center | Dallas | Texas | United States | 75390 |
Sponsors and Collaborators
- University of Texas Southwestern Medical Center
- National Heart, Lung, and Blood Institute (NHLBI)
Investigators
- Principal Investigator: Wanpen Vongpatanasin, MD, University of Texas, Southwestern Medical Center at Dallas
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 413
- R01HL078782-02
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | 119 subjects failed screening. 30 patients undergo 2-phase crossover study (chlorthalidone vs. spironolactone). 7 patients dropped out, 23 subjects completed study#1. 17 subjects undergo 3-phase study (chlorthalidone+placebo, chlorthalidone+spironolactone, and chlorthalidone+ irbesartan). 1 patients dropped out. 16 subjects completed study#2. |
| Arm/Group Title | Study#1: Chlorthalidone (CTD) First Then Spironolactone (SP) | Study #1: Spironolactone (SP) First, Then Chlorthalidone (CTD) | Study# 2 CTD Alone 1st, CTD+ SP 2nd, CTD+IR 3rd | Study# 2 CTD Alone 1st, CTD+IR 2nd, CTD+SP3rd | Study# 2 CTD+SP1st, CTD Alone 2nd, CTD+IR 3rd | Study# 2 CTD+SP1st, CTD+IR 2nd, CTD Alone 3rd | Study# 2 CTD+IR 1st, CTD Alone 2nd, CTD+SP 3rd | Study# 2 CTD+IR 1st, CTD+SP 2nd, CTD Alone 3rd |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. |
| Period Title: First Intervention - 3 Months | ||||||||
| STARTED | 15 | 15 | 6 | 7 | 3 | 0 | 1 | 0 |
| COMPLETED | 12 | 11 | 6 | 7 | 3 | 0 | 1 | 0 |
| NOT COMPLETED | 3 | 4 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period Title: First Intervention - 3 Months | ||||||||
| STARTED | 12 | 11 | 6 | 7 | 3 | 0 | 1 | 0 |
| COMPLETED | 12 | 11 | 6 | 7 | 3 | 0 | 1 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period Title: First Intervention - 3 Months | ||||||||
| STARTED | 0 | 0 | 6 | 7 | 3 | 0 | 1 | 0 |
| COMPLETED | 0 | 0 | 6 | 6 | 3 | 0 | 1 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Participants Study#1 | Participants Study#2 | Total |
|---|---|---|---|
| Arm/Group Description | study #1 has 2 arms. Arm 1. chlorthalidone (CTD) first then spironolactone (SP): subjects are randomized to receive 3 months of CTD first (12.5-25 mg/d), titrated to achieve 24-h BP < 130/80 mmHg. Then, the subject is transitioned to treatment with spironolactone (25-75 mg/d) without washout period for 3 months. Following 3 month treatment period, sympathetic nerve activity, 24 h-ambulatory BP, fasting plasma glucose, insulin, HOMA IR, and baroreflex sensitivity are measured. After completion of the study procedures, the medication is discontinued. Arm 2. spironolactone (SP) first, then chlorthalidone (CTD): subjects are randomized to receive 3 months spironolactone first (25-75 mg/d), titrated to achieve 24-h BP < 130/80 mmHg. Then, the subject is switched to CTD (12.5-25 mg/d) without washout period. Following 3 month treatment period, sympathetic nerve activity, 24 h-ambulatory BP, fasting plasma glucose, insulin, HOMA IR, and baroreflex sensitivity are measured. | study #2 has 6 arms. Arm 1. CTD alone 1st, CTD+ SP 2nd, CTD+IR 3rd: 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. Arm 2. fixed-dose CTD alone 1st, CTD+IR 2nd, CTD+SP3rd Arm3. fixed-dose CTD+SP1st, CTD alone 2nd, CTD+IR 3rd Arm 4. fixed-dose CTD+SP1st, CTD+IR 2nd, CTD alone 3rd Arm 5. CTD+IR 1st, CTD alone 2nd, CTD+SP 3rd Arm 6. CTD+IR 1st, CTD+SP 2nd, CTD alone 3rd | Total of all reporting groups |
| Overall Participants | 30 | 17 | 47 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
49.3
(2.0)
|
50.6
(2.3)
|
49.7
(2.2)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
9
30%
|
4
23.5%
|
13
27.7%
|
| Male |
21
70%
|
13
76.5%
|
34
72.3%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
30
100%
|
17
100%
|
47
100%
|
Outcome Measures
| Title | Sympathetic Nerve Activity |
|---|---|
| Description | |
| Time Frame | Measured at 3 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Study#1: Chlorthalidone (CTD), Titrated Dose | Study #1: Spironolactone (SP), Titrated Dose | Study# 2 Chlorthalidone (CTD), Fixed Dose | Study# 2 CTD Fixed Dose 25 mg/d Plus SP Fixed Dose | Study# 2 CTD Fixed Dose 25 mg/d Plus IR Fixed Dose |
|---|---|---|---|---|---|
| Arm/Group Description | Participants in study #1 only received 2 interventions. All subjects are randomized to receive 3 months of chlorthalidone first (12.5-25 mg/d) or spironolactone (25-75 mg/d) first at the dose titrated to achieve 24-h ambulatory BP < 130/80 mmHg, using a single-blind 2-phase crossover design. Then, the subject is transitioned to treatment the remain arm without washout period for 3 months. Following 3 month treatment period, measurement of outcomes are performed. After completion of the study procedures, the medication is discontinued. | Participants in study #1 only received 2 interventions. All subjects are randomized to receive 3 months of spironolactone (25-75 mg/d) first or chlorthalidone first (12.5-25 mg/d) at the dose titrated to achieve 24-h ambulatory BP < 130/80 mmHg, using a single-blind 2-phase crossover design. Then, the subject is transitioned to treatment the remain arm without washout period for 3 months. Following 3 month treatment period, measurement of outcomes are performed. After completion of the study procedures, the medication is discontinued. | Subjects are randomized to receive 3 months of fixed-dose chlorthalidone (CTD, 25 mg/d) alone first or fixed-dose CTD (25 mg/d) plus fixed-dose spironolactone (SP) 25 mg daily first or fixed-dose CTD (25 mg/d) plus fixed-dose irbsesartan (IR, 150 mg daily) first, using a single-blind 3-phase crossover design. Then, subjects are treated with the remaining one of the 2 arms for 3 months, followed by the last arm for 3 months without washout period. After completion of the study procedures, the medication is discontinued. | Subjects are randomized to receive 3 months of fixed-dose chlorthalidone (CTD, 25 mg/d) alone first or fixed-dose CTD (25 mg/d) plus fixed-dose spironolactone (SP) 25 mg daily first or fixed-dose CTD (25 mg/d) plus fixed-dose irbsesartan (IR, 150 mg daily) first, using a single-blind 3-phase crossover design. Then, subjects are treated with the remaining one of the 2 arms for 3 months, followed by the last arm for 3 months without washout period. After completion of the study procedures, the medication is discontinued. | Subjects are randomized to receive 3 months of fixed-dose chlorthalidone (CTD, 25 mg/d) alone first or fixed-dose CTD (25 mg/d) plus fixed-dose spironolactone (SP) 25 mg daily first or fixed-dose CTD (25 mg/d) plus fixed-dose irbsesartan (IR, 150 mg daily) first, using a single-blind 3-phase crossover design. Then, subjects are treated with the remaining one of the 2 arms for 3 months, followed by the last arm for 3 months without washout period. After completion of the study procedures, the medication is discontinued. |
| Measure Participants | 23 | 23 | 17 | 17 | 17 |
| Mean (Standard Error) [bursts/min] |
46
(4)
|
40
(3)
|
49
(3)
|
42
(3)
|
52
(2)
|
| Title | 24-hour Ambulatory Systolic Blood Pressure |
|---|---|
| Description | |
| Time Frame | Measured at 3 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Study#1: Chlorthalidone (CTD), Titrated Dose | Study #1: Spironolactone (SP), Titrated Dose | Study# 2 Chlorthalidone (CTD), Fixed Dose | Study# 2 CTD Fixed Dose 25 mg/d Plus SP Fixed Dose | Study# 2 CTD Fixed Dose 25 mg/d Plus IR Fixed Dose |
|---|---|---|---|---|---|
| Arm/Group Description | Participants in study #1 only received 2 interventions. All subjects are randomized to receive 3 months of chlorthalidone first (12.5-25 mg/d) or spironolactone (25-75 mg/d) first at the dose titrated to achieve 24-h ambulatory BP < 130/80 mmHg, using a single-blind 2-phase crossover design. Then, the subject is transitioned to treatment the remain arm without washout period for 3 months. Following 3 month treatment period, measurement of outcomes are performed. After completion of the study procedures, the medication is discontinued. | Participants in study #1 only received 2 interventions. All subjects are randomized to receive 3 months of chlorthalidone first (12.5-25 mg/d) or spironolactone (25-75 mg/d) first at the dose titrated to achieve 24-h ambulatory BP < 130/80 mmHg, using a single-blind 2-phase crossover design. Then, the subject is transitioned to treatment the remain arm without washout period for 3 months. Following 3 month treatment period, measurement of outcomes are performed. After completion of the study procedures, the medication is discontinued. | Subjects are randomized to receive 3 months of fixed-dose chlorthalidone (CTD, 25 mg/d) alone first or fixed-dose CTD (25 mg/d) plus fixed-dose spironolactone (SP) 25 mg daily first or fixed-dose CTD (25 mg/d) plus fixed-dose irbsesartan (IR, 150 mg daily) first, using a single-blind 3-phase crossover design. Then, subjects are treated with the remaining one of the 2 arms for 3 months, followed by the last arm for 3 months without washout period. After completion of the study procedures, the medication is discontinued. | Subjects are randomized to receive 3 months of fixed-dose chlorthalidone (CTD, 25 mg/d) alone first or fixed-dose CTD (25 mg/d) plus fixed-dose spironolactone (SP) 25 mg daily first or fixed-dose CTD (25 mg/d) plus fixed-dose irbsesartan (IR, 150 mg daily) first, using a single-blind 3-phase crossover design. Then, subjects are treated with the remaining one of the 2 arms for 3 months, followed by the last arm for 3 months without washout period. After completion of the study procedures, the medication is discontinued. | Subjects are randomized to receive 3 months of fixed-dose chlorthalidone (CTD, 25 mg/d) alone first or fixed-dose CTD (25 mg/d) plus fixed-dose spironolactone (SP) 25 mg daily first or fixed-dose CTD (25 mg/d) plus fixed-dose irbsesartan (IR, 150 mg daily) first, using a single-blind 3-phase crossover design. Then, subjects are treated with the remaining one of the 2 arms for 3 months, followed by the last arm for 3 months without washout period. After completion of the study procedures, the medication is discontinued. |
| Measure Participants | 23 | 23 | 17 | 17 | 17 |
| Mean (Standard Error) [mmHg] |
127.4
(2)
|
128.6
(2)
|
123.5
(2)
|
121.6
(3)
|
119.8
(3)
|
| Title | Insulin |
|---|---|
| Description | fasting plasma insulin |
| Time Frame | 3 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Study#1: Chlorthalidone (CTD), Titrated Dose | Study #1: Spironolactone (SP), Titrated Dose | Study# 2 CTD Fixed Dose 25 mg/d | Study# 2 CTD Fixed Dose 25 mg/d Plus SP Fixed Dose | Study# 2 CTD Fixed Dose 25 mg/d Plus IR Fixed Dose |
|---|---|---|---|---|---|
| Arm/Group Description | Participants in study #1 only received 2 interventions. All subjects are randomized to receive 3 months of chlorthalidone first (12.5-25 mg/d) or spironolactone (25-75 mg/d) first at the dose titrated to achieve 24-h ambulatory BP < 130/80 mmHg, using a single-blind 2-phase crossover design. Then, the subject is transitioned to treatment the remain arm without washout period for 3 months. Following 3 month treatment period, measurement of outcomes are performed. After completion of the study procedures, the medication is discontinued. | Participants in study #1 only received 2 interventions. All subjects are randomized to receive 3 months of spironolactone (25-75 mg/d) first or chlorthalidone first (12.5-25 mg/d) at the dose titrated to achieve 24-h ambulatory BP < 130/80 mmHg, using a single-blind 2-phase crossover design. Then, the subject is transitioned to treatment the remain arm without washout period for 3 months. Following 3 month treatment period, measurement of outcomes are performed. After completion of the study procedures, the medication is discontinued. | Subjects are randomized to receive 3 months of fixed-dose chlorthalidone (CTD, 25 mg/d) alone first or fixed-dose CTD (25 mg/d) plus fixed-dose spironolactone (SP) 25 mg daily first or fixed-dose CTD (25 mg/d) plus fixed-dose irbsesartan (IR, 150 mg daily) first, using a single-blind 3-phase crossover design. Then, subjects are treated with the remaining one of the 2 arms for 3 months, followed by the last arm for 3 months without washout period. After completion of the study procedures, the medication is discontinued. | Subjects are randomized to receive 3 months of fixed-dose chlorthalidone (CTD, 25 mg/d) alone first or fixed-dose CTD (25 mg/d) plus fixed-dose spironolactone (SP) 25 mg daily first or fixed-dose CTD (25 mg/d) plus fixed-dose irbsesartan (IR, 150 mg daily) first, using a single-blind 3-phase crossover design. Then, subjects are treated with the remaining one of the 2 arms for 3 months, followed by the last arm for 3 months without washout period. After completion of the study procedures, the medication is discontinued. | Subjects are randomized to receive 3 months of fixed-dose chlorthalidone (CTD, 25 mg/d) alone first or fixed-dose CTD (25 mg/d) plus fixed-dose spironolactone (SP) 25 mg daily first or fixed-dose CTD (25 mg/d) plus fixed-dose irbsesartan (IR, 150 mg daily) first, using a single-blind 3-phase crossover design. Then, subjects are treated with the remaining one of the 2 arms for 3 months, followed by the last arm for 3 months without washout period. After completion of the study procedures, the medication is discontinued. |
| Measure Participants | 23 | 23 | 17 | 17 | 17 |
| Median (Inter-Quartile Range) [mU/liter] |
8.24
|
7.6
|
7.6
|
4.87
|
6.8
|
| Title | HOMA-IR |
|---|---|
| Description | assessment of insulin resistance calculated by multiplying fasting plasma insulin (mU/l) with fasting plasma glucose (mmol/l) divided by 22.5. |
| Time Frame | 3 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| unequal randomization by chance |
| Arm/Group Title | Study#1: Chlorthalidone (CTD), Titrated Dose | Study #1: Spironolactone (SP), Titrated Dose | Study# 2 Chlorthalidone (CTD), Fixed Dose | Study# 2 CTD Fixed Dose 25 mg/d Plus SP Fixed Dose | Study# 2 CTD Fixed Dose 25 mg/d Plus IR Fixed Dose |
|---|---|---|---|---|---|
| Arm/Group Description | Participants in study #1 only received 2 interventions. All subjects are randomized to receive 3 months of chlorthalidone first (12.5-25 mg/d) or spironolactone (25-75 mg/d) first at the dose titrated to achieve 24-h ambulatory BP < 130/80 mmHg, using a single-blind 2-phase crossover design. Then, the subject is transitioned to treatment the remain arm without washout period for 3 months. Following 3 month treatment period, measurement of outcomes are performed. After completion of the study procedures, the medication is discontinued. | Participants in study #1 only received 2 interventions. All subjects are randomized to receive 3 months of spironolactone (25-75 mg/d) first or chlorthalidone first (12.5-25 mg/d) at the dose titrated to achieve 24-h ambulatory BP < 130/80 mmHg, using a single-blind 2-phase crossover design. Then, the subject is transitioned to treatment the remain arm without washout period for 3 months. Following 3 month treatment period, measurement of outcomes are performed. After completion of the study procedures, the medication is discontinued. | Subjects are randomized to receive 3 months of fixed-dose chlorthalidone (CTD, 25 mg/d) alone first or fixed-dose CTD (25 mg/d) plus fixed-dose spironolactone (SP) 25 mg daily first or fixed-dose CTD (25 mg/d) plus fixed-dose irbsesartan (IR, 150 mg daily) first, using a single-blind 3-phase crossover design. Then, subjects are treated with the remaining one of the 2 arms for 3 months, followed by the last arm for 3 months without washout period. After completion of the study procedures, the medication is discontinued. | Subjects are randomized to receive 3 months of fixed-dose chlorthalidone (CTD, 25 mg/d) alone first or fixed-dose CTD (25 mg/d) plus fixed-dose spironolactone (SP) 25 mg daily first or fixed-dose CTD (25 mg/d) plus fixed-dose irbsesartan (IR, 150 mg daily) first, using a single-blind 3-phase crossover design. Then, subjects are treated with the remaining one of the 2 arms for 3 months, followed by the last arm for 3 months without washout period. After completion of the study procedures, the medication is discontinued. | Subjects are randomized to receive 3 months of fixed-dose chlorthalidone (CTD, 25 mg/d) alone first or fixed-dose CTD (25 mg/d) plus fixed-dose spironolactone (SP) 25 mg daily first or fixed-dose CTD (25 mg/d) plus fixed-dose irbsesartan (IR, 150 mg daily) first, using a single-blind 3-phase crossover design. Then, subjects are treated with the remaining one of the 2 arms for 3 months, followed by the last arm for 3 months without washout period. After completion of the study procedures, the medication is discontinued. |
| Measure Participants | 23 | 23 | 17 | 17 | 17 |
| Median (Inter-Quartile Range) [mU/l*mmol/l] |
1.91
|
1.33
|
1.87
|
0.85
|
1.42
|
| Title | Sympathetic Baroreflex Sensitivity |
|---|---|
| Description | slope relating percent change in SNA (% change in total activity from baseline) to diastolic BP. |
| Time Frame | 3 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Study#1: Chlorthalidone (CTD), Titrated Dose | Drug: Study #1: Spironolactone (SP), Titrated Dose | Study# 2 Chlorthalidone (CTD), Fixed Dose | Study# 2 CTD Fixed Dose 25 mg/d Plus SP Fixed Dose | Study# 2 CTD Fixed Dose 25 mg/d Plus IR Fixed Dose |
|---|---|---|---|---|---|
| Arm/Group Description | Participants in study #1 only received 2 interventions. All subjects are randomized to receive 3 months of chlorthalidone first (12.5-25 mg/d) or spironolactone (25-75 mg/d) first at the dose titrated to achieve 24-h ambulatory BP < 130/80 mmHg, using a single-blind 2-phase crossover design. Then, the subject is transitioned to treatment the remain arm without washout period for 3 months. Following 3 month treatment period, measurement of outcomes are performed. After completion of the study procedures, the medication is discontinued. | Participants in study #1 only received 2 interventions. All subjects are randomized to receive 3 months of spironolactone (25-75 mg/d) first or chlorthalidone first (12.5-25 mg/d) at the dose titrated to achieve 24-h ambulatory BP < 130/80 mmHg, using a single-blind 2-phase crossover design. Then, the subject is transitioned to treatment the remain arm without washout period for 3 months. Following 3 month treatment period, measurement of outcomes are performed. After completion of the study procedures, the medication is discontinued. | Subjects are randomized to receive 3 months of fixed-dose chlorthalidone (CTD, 25 mg/d) alone first or fixed-dose CTD (25 mg/d) plus fixed-dose spironolactone (SP) 25 mg daily first or fixed-dose CTD (25 mg/d) plus fixed-dose irbsesartan (IR, 150 mg daily) first, using a single-blind 3-phase crossover design. Then, subjects are treated with the remaining one of the 2 arms for 3 months, followed by the last arm for 3 months without washout period. After completion of the study procedures, the medication is discontinued. | Subjects are randomized to receive 3 months of fixed-dose chlorthalidone (CTD, 25 mg/d) alone first or fixed-dose CTD (25 mg/d) plus fixed-dose spironolactone (SP) 25 mg daily first or fixed-dose CTD (25 mg/d) plus fixed-dose irbsesartan (IR, 150 mg daily) first, using a single-blind 3-phase crossover design. Then, subjects are treated with the remaining one of the 2 arms for 3 months, followed by the last arm for 3 months without washout period. After completion of the study procedures, the medication is discontinued. | Subjects are randomized to receive 3 months of fixed-dose chlorthalidone (CTD, 25 mg/d) alone first or fixed-dose CTD (25 mg/d) plus fixed-dose spironolactone (SP) 25 mg daily first or fixed-dose CTD (25 mg/d) plus fixed-dose irbsesartan (IR, 150 mg daily) first, using a single-blind 3-phase crossover design. Then, subjects are treated with the remaining one of the 2 arms for 3 months, followed by the last arm for 3 months without washout period. After completion of the study procedures, the medication is discontinued. |
| Measure Participants | 23 | 23 | 17 | 17 | 17 |
| Mean (Standard Deviation) [% change from baseline per mmHg] |
-9.1
(3.8)
|
-15.2
(3.2)
|
-12.9
(7.8)
|
-11.3
(8.8)
|
-12.0
(7)
|
Adverse Events
| Time Frame | 3 months | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||
| Arm/Group Title | Study#1: Chlorthalidone (CTD), Titrated Dose | Study #1: Spironolactone (SP), Titrated Dose | Study# 2 Chlorthalidone (CTD), Fixed Dose | Study# 2 CTD Fixed Dose 25 mg/d Plus SP Fixed Dose | Study# 2 CTD Fixed Dose 25 mg/d Plus IR Fixed Dose | |||||
| Arm/Group Description | Participants in study #1 only received 2 interventions. All subjects are randomized to receive 3 months of chlorthalidone first (12.5-25 mg/d) or spironolactone (25-75 mg/d) first at the dose titrated to achieve 24-h ambulatory BP < 130/80 mmHg, using a single-blind 2-phase crossover design. Then, the subject is transitioned to treatment the remain arm without washout period for 3 months. Following 3 month treatment period, measurement of outcomes are performed. After completion of the study procedures, the medication is discontinued. | Participants in study #1 only received 2 interventions. All subjects are randomized to receive 3 months of spironolactone (25-75 mg/d) first or chlorthalidone first (12.5-25 mg/d) at the dose titrated to achieve 24-h ambulatory BP < 130/80 mmHg, using a single-blind 2-phase crossover design. Then, the subject is transitioned to treatment the remain arm without washout period for 3 months. Following 3 month treatment period, measurement of outcomes are performed. After completion of the study procedures, the medication is discontinued. | Subjects are randomized to receive 3 months of fixed-dose chlorthalidone (CTD, 25 mg/d) alone first or fixed-dose CTD (25 mg/d) plus fixed-dose spironolactone (SP) 25 mg daily first or fixed-dose CTD (25 mg/d) plus fixed-dose irbsesartan (IR, 150 mg daily) first, using a single-blind 3-phase crossover design. Then, subjects are treated with the remaining one of the 2 arms for 3 months, followed by the last arm for 3 months without washout period. After completion of the study procedures, the medication is discontinued. | Subjects are randomized to receive 3 months of fixed-dose chlorthalidone (CTD, 25 mg/d) alone first or fixed-dose CTD (25 mg/d) plus fixed-dose spironolactone (SP) 25 mg daily first or fixed-dose CTD (25 mg/d) plus fixed-dose irbsesartan (IR, 150 mg daily) first, using a single-blind 3-phase crossover design. Then, subjects are treated with the remaining one of the 2 arms for 3 months, followed by the last arm for 3 months without washout period. After completion of the study procedures, the medication is discontinued. | Subjects are randomized to receive 3 months of fixed-dose chlorthalidone (CTD, 25 mg/d) alone first or fixed-dose CTD (25 mg/d) plus fixed-dose spironolactone (SP) 25 mg daily first or fixed-dose CTD (25 mg/d) plus fixed-dose irbsesartan (IR, 150 mg daily) first, using a single-blind 3-phase crossover design. Then, subjects are treated with the remaining one of the 2 arms for 3 months, followed by the last arm for 3 months without washout period. After completion of the study procedures, the medication is discontinued. | |||||
All Cause Mortality |
||||||||||
| Study#1: Chlorthalidone (CTD), Titrated Dose | Study #1: Spironolactone (SP), Titrated Dose | Study# 2 Chlorthalidone (CTD), Fixed Dose | Study# 2 CTD Fixed Dose 25 mg/d Plus SP Fixed Dose | Study# 2 CTD Fixed Dose 25 mg/d Plus IR Fixed Dose | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/26 (0%) | 0/27 (0%) | 0/17 (0%) | 0/17 (0%) | 0/17 (0%) | |||||
Serious Adverse Events |
||||||||||
| Study#1: Chlorthalidone (CTD), Titrated Dose | Study #1: Spironolactone (SP), Titrated Dose | Study# 2 Chlorthalidone (CTD), Fixed Dose | Study# 2 CTD Fixed Dose 25 mg/d Plus SP Fixed Dose | Study# 2 CTD Fixed Dose 25 mg/d Plus IR Fixed Dose | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/26 (0%) | 0/27 (0%) | 0/17 (0%) | 0/17 (0%) | 0/17 (0%) | |||||
Other (Not Including Serious) Adverse Events |
||||||||||
| Study#1: Chlorthalidone (CTD), Titrated Dose | Study #1: Spironolactone (SP), Titrated Dose | Study# 2 Chlorthalidone (CTD), Fixed Dose | Study# 2 CTD Fixed Dose 25 mg/d Plus SP Fixed Dose | Study# 2 CTD Fixed Dose 25 mg/d Plus IR Fixed Dose | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/26 (3.8%) | 0/27 (0%) | 0/17 (0%) | 0/17 (0%) | 0/17 (0%) | |||||
| Cardiac disorders | ||||||||||
| chest pain | 1/26 (3.8%) | 1 | 0/27 (0%) | 1 | 0/17 (0%) | 1 | 0/17 (0%) | 1 | 0/17 (0%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Wanpen Vongpatanasin |
|---|---|
| Organization | University of Texas Southwestern Medical Center |
| Phone | 2146458000 |
| wanpen.vongpatanasin@utsouthwestern.edu |
- 413
- R01HL078782-02