Metabolic Effects of Antihypertensive Drugs on People With Metabolic Syndrome (The MEAD Study) (MEAD)

• ClinicalTrials.gov Identifier: NCT00887510
• Recruitment Status: Completed
• First Posted: April 24, 2009
• Results First Posted: June 17, 2014
• Last Update Posted: June 17, 2014
• Sponsor: University of Florida
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
• Information provided by (Responsible Party): University of Florida

Study Description

Brief Summary:

High blood pressure, also referred to as hypertension, is a blood pressure level of 140/90 mm Hg or higher. Along with lifestyle changes, various medications are currently used to treat people with hypertension. Some of these medications, however, may affect the way the body handles sugar, essentially preventing the body from breaking down sugar and predisposing people to developing diabetes. People who have metabolic syndrome-a condition primarily characterized by an increased waist measurement, abnormal blood lipid levels, hypertension, and high blood sugar levels-are already at risk of developing diabetes. In these people, taking the antihypertensive medications that prevent sugar breakdown may further increase their risk of diabetes. The purpose of this study is to gain an understanding of how people with metabolic syndrome respond to antihypertensive medications that alter the body's ability to break down sugar.

Condition or disease	Intervention/treatment	Phase
Hypertension	Drug: Hydrochlorothiazide; Drug: Trandolapril	Phase 4

Detailed Description:

Treatment for hypertension includes lifestyle changes and medications. Examples of some antihypertensive medications include diuretics, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and vasodilators. Mounting research suggests that certain antihypertensive medications, such as thiazide diuretics, are associated with metabolic disturbances that result in increased glucose intolerance, while other antihypertensive medications, such as ACE inhibitors and ARBs, appear to improve insulin sensitivity and glucose metabolism. The influence of these medications may be especially critical in people with metabolic syndrome, who are already at risk of developing glucose intolerance and diabetes. The purpose of this study is to gain an understanding of how people with metabolic syndrome respond to antihypertensive medications that alter the body's ability to break down sugar. The long-term goal of the study is to determine the best antihypertensive medications for people who have both metabolic syndrome and hypertension so as to prevent or delay the onset of diabetes in this population.

Participation in this study will last 18 weeks and involve four study visits. Participants will be randomly assigned to initially receive 6 weeks of treatment with either hydrochlorothiazide (HCTZ), which is a thiazide diuretic, or trandolapril, which is an ACE inhibitor. Both medications are FDA-approved for treating hypertension. After 6 weeks of treatment, if participants' blood pressure levels are not too low, they will add the second medication so that they are taking both HCTZ and trandolapril for the next 6 weeks, until Week 12. At Week 12, again if participants' blood pressure levels are not too low, they will then take only the second medication for the last 6 weeks. The four study visits will occur at baseline and after each of the three 6-week treatment periods (Weeks 6, 12, and 18). All study visits will include blood pressure and pulse measurements, urine and blood sampling, oral glucose tolerance testing, and questions about diet and exercise habits. The first and last study visits will also include a physical examination and a medical history review. Some of the blood collected during the first study visit will be used for genetic testing. There will be no follow-up visits.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Metabolic Effects of Antihypertensive Drugs
• Study Start Date: May 2007
• Actual Primary Completion Date: November 2009
• Actual Study Completion Date: November 2009

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Thiazide First; Participants will receive 25 mg of hydrochlorothiazide (HCTZ) each day for 6 weeks, followed by 25 mg of HCTZ every day plus 4 mg of trandolapril each day for 6 weeks, followed by 4 mg trandolapril each day for 6 weeks.	Drug: Hydrochlorothiazide; 25 mg tablet once daily for 6 weeks Other Names: HCTZ; Drug: Trandolapril; 4 mg tablet once daily for 6 weeks
Active Comparator: Trandolapril First; Participants will receive 4 mg of trandolapril each day for 6 weeks, followed by 4 mg of trandolapril for 6 weeks plus 25 mg of HCTZ each day for 6 weeks, followed by 25 mg of HCTZ each day for 6 weeks.	Drug: Hydrochlorothiazide; 25 mg tablet once daily for 6 weeks Other Names: HCTZ; Drug: Trandolapril; 4 mg tablet once daily for 6 weeks

Outcome Measures

Primary Outcome Measures :

1. Change in Oral Glucose Tolerance Test (OGTT) Area Under Curve (AUC) After Addition of Trandolapril to Hydrochlorothiazide (HCTZ) Compared With Change in OGTT AUC After Addition of HCTZ to Trandolapril [ Time Frame: OGTT AUC measured over 120 minutes after receiving study intervention for 18-24 weeks. ]
   Comparing the change in OGTT AUC rand 1 visit4-visit 3 with rand 2 visit 3-2. This allows for understanding the effects of addition of trandolapril to 12 weeks of HCTZ compared with addition of HCTZ to 12 weeks of trandolapril. This is the primary outcome of the study.

Secondary Outcome Measures :

1. Change in Total Adiponectin Level After Addition of Trandolapril to HCTZ Compared With Change in Adiponectin After Addition of HCTZ to Trandolapril [ Time Frame: Over the course of 18 weeks ]

   Comparing the change in adiponectin: rand 1 visit4-visit 3 with rand 2 visit 3-2.

   This allows for understanding the effects of addition of trandolapril to 12 weeks of HCTZ compared with addition of HCTZ to 12 weeks of trandolapril.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Hypertension, defined as systolic blood pressure greater than or equal to 130 but less than 160 mm Hg and diastolic blood pressure greater than or equal to 85 but less than 110 mm Hg

• Must have any two of the following criteria:

  1. Abdominal obesity, defined as a waist circumference greater than 40 inches in men and greater than 35 inches in women
  2. High-density lipoprotein (HDL) cholesterol level of less than 40 mg/dL in men and less than 50 mg/dL in women
  3. Fasting triglycerides greater than or equal to 150 mg/dL
  4. Fasting glucose level of 100-125 mg/dL

Exclusion Criteria:

• Significant hypertension (greater than 160/110 mm Hg)
• Isolated systolic hypertension
• Diseases requiring treatment with diuretics or angiotensin-converting enzyme (ACE) inhibitors
• Cardiovascular disease (history of heart attack, stroke, heart failure)
• Hypersensitivity to HCTZ or ACE inhibitor
• Type 1 or type 2 diabetes
• Hypokalemia
• Peri-menopause (symptom onset within 1 year)
• Pregnant or breastfeeding
• Secondary causes of hypertension
• Current use of antihypertensive medications known to affect glucose homeostasis (e.g., diuretics, beta blockers, corticosteroids, ACE inhibitors, angiotensin receptor blockers [ARBs])

Contacts and Locations

Locations

United States, Florida

University of Florida

Gainesville, Florida, United States, 32610

Sponsors and Collaborators

University of Florida

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: Rhonda M. Cooper-DeHoff, Pharm D, MS; University of Florida

More Information

• Responsible Party: University of Florida
• ClinicalTrials.gov Identifier: NCT00887510
• Other Study ID Numbers: 650; K23HL086558 ( U.S. NIH Grant/Contract )
• First Posted: April 24, 2009
• Results First Posted: June 17, 2014
• Last Update Posted: June 17, 2014
• Last Verified: June 2014

Keywords provided by University of Florida:

Metabolic Syndrome; High Blood Pressure; Abdominal Obesity; Impaired Glucose Tolerance

Additional relevant MeSH terms:

Metabolic Syndrome; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Hydrochlorothiazide; Trandolapril; Antihypertensive Agents; Diuretics; Natriuretic Agents; Physiological Effects of Drugs; Sodium Chloride Symporter Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Angiotensin-Converting Enzyme Inhibitors; Protease Inhibitors; Enzyme Inhibitors