- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00887510
Metabolic Effects of Antihypertensive Drugs on People With Metabolic Syndrome (The MEAD Study) (MEAD)
Metabolic Effects of Antihypertensive Drugs
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
Florida
-
Gainesville, Florida, United States, 32610
- University of Florida
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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:
- Abdominal obesity, defined as a waist circumference greater than 40 inches in men and greater than 35 inches in women
- High-density lipoprotein (HDL) cholesterol level of less than 40 mg/dL in men and less than 50 mg/dL in women
- Fasting triglycerides greater than or equal to 150 mg/dL
- 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])
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / 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.
|
25 mg tablet once daily for 6 weeks Other Names: HCTZ
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.
|
25 mg tablet once daily for 6 weeks Other Names: HCTZ
4 mg tablet once daily for 6 weeks
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
OGTT AUC measured over 120 minutes after receiving study intervention for 18-24 weeks.
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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. |
Over the course of 18 weeks
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Rhonda M. Cooper-DeHoff, Pharm D, MS, University of Florida
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Glucose Metabolism Disorders
- Metabolic Diseases
- Insulin Resistance
- Hyperinsulinism
- Metabolic Syndrome
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antihypertensive Agents
- Enzyme Inhibitors
- Protease Inhibitors
- Natriuretic Agents
- Membrane Transport Modulators
- Diuretics
- Angiotensin-Converting Enzyme Inhibitors
- Sodium Chloride Symporter Inhibitors
- Hydrochlorothiazide
- Trandolapril
Other Study ID Numbers
- 650
- K23HL086558 (U.S. NIH Grant/Contract)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Hypertension
-
National Taiwan University Hospital Hsin-Chu BranchRecruitingHypertension,Essential | Hypertension, MaskedTaiwan
-
BayerCompletedPrimary HypertensionChina
-
University of Alabama at BirminghamTroy UniversityCompletedHypertension | Hypertension, Resistant to Conventional Therapy | Uncontrolled Hypertension | Hypertension, White CoatUnited States
-
Columbia UniversityAgency for Healthcare Research and Quality (AHRQ)Active, not recruitingWhite Coat Hypertension | Hypertension,EssentialUnited States
-
Addpharma Inc.Completed
-
Universidade Federal de Santa MariaCompletedHealthy Volunteers | Hypertension, EssentialBrazil
-
Sheffield Teaching Hospitals NHS Foundation TrustUniversity of SheffieldCompletedIdiopathic Pulmonary Arterial Hypertension | Chronic Thromboembolic Pulmonary HypertensionUnited Kingdom
-
China Academy of Chinese Medical SciencesGuang'anmen Hospital of China Academy of Chinese Medical SciencesCompletedHypertension, Resistant to Conventional Therapy | Primary HypertensionChina
-
Cytos Biotechnology AGCompletedMild Essential Hypertension | Moderate Essential HypertensionSwitzerland
Clinical Trials on Hydrochlorothiazide
-
Insel Gruppe AG, University Hospital BernCompleted
-
Mylan Pharmaceuticals IncCompletedHealthyUnited States
-
Sir Mortimer B. Davis - Jewish General HospitalNovartis PharmaceuticalsWithdrawnHypertension | DiabetesCanada
-
Daiichi Sankyo, Inc.CompletedEssential HypertensionFrance, Poland, Ukraine, Belgium, Germany, Spain, Bulgaria, Romania, Denmark, Russian Federation, Netherlands, Austria, Slovakia, Czechia
-
SanofiCompletedHypertensionIndia, Malaysia, Philippines, Singapore, Taiwan, Tunisia, Egypt, Korea, Republic of, Hong Kong, Indonesia, Morocco, Pakistan, Thailand, Vietnam
-
Daiichi Sankyo, Inc.Daiichi Sankyo Europe, GmbH, a Daiichi Sankyo CompanyCompletedEssential HypertensionFrance, Poland, Ukraine, Germany, Spain, Bulgaria, Czechia
-
Spanish Society of Internal MedicineCompleted
-
University Hospital, Strasbourg, FranceSuspendedHypertension | End Stage Renal Disease | ProteinuriaFrance
-
IPCA Laboratories Ltd.Completed
-
Capital Medical UniversityRecruiting