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