Evaluating the Link Between Thiazide Medications, the Nervous System, and Diabetes in Individuals With High Blood Pressure - Full Text View

Sponsor:	National Heart, Lung, and Blood Institute (NHLBI)
Information provided by:	National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier:	NCT00353652

Purpose

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	Intervention	Phase
Hypertension	Drug: Chlorthalidone Drug: Spironolactone Drug: Eplerenone Drug: Quinapril Drug: Irbesartan	Phase IV

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Crossover Assignment Masking: Single Blind (Subject) Primary Purpose: Prevention
Official Title:	Neural Mechanisms of Thiazide-induced Insulin Resistance

Resource links provided by NLM:

Genetics Home Reference related topics: 6q24-related transient neonatal diabetes mellitus

MedlinePlus related topics: Diabetes Medicines High Blood Pressure

Drug Information available for: Spironolactone Quinapril hydrochloride Quinapril Chlorthalidone Irbesartan

U.S. FDA Resources

Further study details as provided by National Heart, Lung, and Blood Institute (NHLBI):

Primary Outcome Measures:

Sympathetic nerve activity [ Time Frame: Measured at 6 months ] [ Designated as safety issue: No ]
24-hour ambulatory blood pressure [ Time Frame: Measured at 6 months ] [ Designated as safety issue: No ]
Insulin sensitivity [ Time Frame: Measured at 6 months ] [ Designated as safety issue: No ]
Forearm blood flow [ Time Frame: Measured at 6 months ] [ Designated as safety issue: No ]
Baroreflex sensitivity [ Time Frame: Measured at 6 months ] [ Designated as safety issue: No ]
C-reactive protein [ Time Frame: Measured at 6 months ] [ Designated as safety issue: No ]
Inflammatory cytokines [ Time Frame: Measured at 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Electrolytes [ Time Frame: Measured at 6 months ] [ Designated as safety issue: No ]
Body weight [ Time Frame: Measured at 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment:	188
Study Start Date:	January 2005
Estimated Study Completion Date:	December 2009
Estimated Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1A	Drug: Chlorthalidone 12.5-25 mg taken orally, once daily Drug: Spironolactone 50-75 mg taken orally, once daily
Experimental: 1C	Drug: Quinapril 20 mg taken orally, once daily Drug: Irbesartan 150 mg taken orally, once daily
Experimental: 2	Drug: Eplerenone 50-100 mg taken orally, once daily
Experimental: 3	Drug: Chlorthalidone 12.5-25 mg taken orally, once daily Drug: Spironolactone 50-75 mg taken orally, once daily

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. Participants will be assigned to one of eight treatment groups. Depending on the assigned group, participants will receive chlorthalidone, spironolactone, quinapril, irbesartan, eplerenone, or a combination of these drugs, with or without placebo. Participants will attend four to six study visits over a period of 16 to 28 weeks. All participants will attend a baseline study visit, which will include a physical examination, a medical history review, vital sign measurements, and blood and urine collection. Small electrodes will be used to measure muscle nerve activity. In addition, blood pressure will be monitored continuously for 24 hours prior to the start of the study. Depending on the assigned treatment group, study visits may include blood collection, blood pressure monitoring, an electrocardiogram (ECG) to record heart activity, nerve function monitoring, and/or plasma volume measurements. Participants' baroreflex sensitivity may also be measured by monitoring nerve ending responses within the heart and blood vessels. Insulin sensitivity will be measured with a glucose tolerance test and by evaluating skeletal muscle glucose uptake.

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00353652

Contacts

Contact: Wanpen Vongpatanasin, MD

214-648-7950

Wanpen.Vongpatanasin@UTSouthwestern.edu

Locations

United States, Texas
University of Texas Southwestern Medical Center at Dallas	Recruiting
Dallas, Texas, United States, 75390
Contact: Debbie Arbique, RN 214-648-2968 debbie.arbique@utsouthwestern.edu
Principal Investigator: Wanpen Vongpatanasin, MD

Sponsors and Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

Principal Investigator:

Wanpen Vongpatanasin, MD

University of Texas Southwestern Medical Center at Dallas

More Information

No publications provided by National Heart, Lung, and Blood Institute (NHLBI)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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. Epub 2010 Jul 21.

Responsible Party:	Wanpen Vongpatanasin, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier:	NCT00353652 History of Changes
Other Study ID Numbers:	413, R01 HL078782-02
Study First Received:	July 18, 2006
Last Updated:	July 28, 2009
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Heart, Lung, and Blood Institute (NHLBI):

Blood Pressure, High

Additional relevant MeSH terms:

Hypertension
Insulin Resistance
Vascular Diseases
Cardiovascular Diseases
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Chlorthalidone
Quinapril
Irbesartan
Spironolactone
Eplerenone
Sodium Chloride Symporter Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action

Pharmacologic Actions
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Aldosterone Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists

ClinicalTrials.gov processed this record on February 09, 2012