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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Wanpen Vongpatanasin, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier:
NCT00353652
First received: July 18, 2006
Last updated: May 27, 2014
Last verified: May 2014
  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 4

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:


Further study details as provided by University of Texas Southwestern Medical Center:

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 ]

Enrollment: 176
Study Start Date: January 2005
Study Completion Date: January 2013
Primary Completion Date: January 2013 (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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, Texas
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390
University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, United States, 75390
Sponsors and Collaborators
University of Texas Southwestern Medical Center
Investigators
Principal Investigator: Wanpen Vongpatanasin, MD University of Texas Southwestern Medical Center at Dallas
  More Information

No publications provided by University of Texas Southwestern Medical Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Wanpen Vongpatanasin, M.D., University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier: NCT00353652     History of Changes
Other Study ID Numbers: 413, R01HL078782-02
Study First Received: July 18, 2006
Last Updated: May 27, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Texas Southwestern Medical Center:
Blood Pressure, High

Additional relevant MeSH terms:
Hypertension
Cardiovascular Diseases
Vascular Diseases
Chlorthalidone
Spironolactone
Antihypertensive Agents
Cardiovascular Agents
Diuretics
Diuretics, Potassium Sparing
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Membrane Transport Modulators
Mineralocorticoid Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Natriuretic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sodium Chloride Symporter Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014