A Randomized Clinical Trial To Study Losartan On Endothelial Dysfunction and Insulin Resistance In Obese Patients

NCT ID: NCT00675987

Last Updated: 2018-09-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 53 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-05-31
• Study Completion Date: 2008-12-31

Brief Summary

The main purposes of this study are to find out if the study drug losartan (Cozaar) or placebo ("sugar pill") has an effect on insulin sensitivity (how your body responds to insulin) and to measure the effect of the study drug losartan or placebo on how the arteries in your arm dilate (enlarge to carry more blood).

We hope to learn if taking losartan changes the amount of certain proteins in the blood that effect blood vessel function.

Losartan is approved by the US FDA to treat high blood pressure. It will take approximately 4 months for you to complete this study.

Conditions

Obesity; Hypertension; Hyperglycemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: QUADRUPLE

Study Groups

Losartan

Losartan 100 mg 1 tab po QD

Group Type: ACTIVE_COMPARATOR

losartan

Intervention Type: DRUG

losartan 100 mg tablets 1 tab po QD

Placebo

Placebo 1 tab po QD

Group Type: PLACEBO_COMPARATOR

Placebo control

Intervention Type: DRUG

Placebo 1 po QD

Interventions

losartan

losartan 100 mg tablets 1 tab po QD

Intervention Type: DRUG

Placebo control

Placebo 1 po QD

Intervention Type: DRUG

Other Intervention Names

Cozaar

Eligibility Criteria

Inclusion Criteria

• Currently taking 1 or no antihypertensive medication
• Male and female between 18 and 75 years of age
• Mean trough sitting diastolic blood pressure (SiDBP) ≥80 and < 100 mm Hg
• Mean trough sitting systolic blood pressure (SiSBP) ≥120 and <160 mm Hg
• Non-diabetic patients with fasting plasma glucose ≥100 mg/dL and <126 mg/dL
• Body mass index (BMI) >30 and <40
• Waist circumference >40 inches in males, > 35 inches in females
• A patient who is of reproductive potential and agrees to remain abstinent or use acceptable methods of birth control (intrauterine device (IUD), diaphragm with spermicide, contraceptive sponge, condom, hormonal contraception, vasectomy) within the projected duration of the study

Exclusion Criteria

• Secondary hypertension of any etiology (renal artery stenosis, coarctation of the aorta or pheochromocytoma, hypertension induced by oral contraceptives)
• History of malignant hypertension
• Any clinically significant renal disease including single functioning kidney, and known history of anuria. Any severe renal impairment, as manifested by serum creatinine more than 1.5 mg/dL, or proteinuria >2+ by urine dipstick
• Known sensitivity or intolerance to angiotensin II receptor antagonists
• Type I or II diabetes
• Inability or unwillingness to abstain from taking prohibited medications during the study period
• History of myocardial infarction (MI), percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG), congestive heart failure (CHF), unstable angina, transient ischemic attack (TIA), or cerebrovascular accident (CVA)
• Concomitant cardiac conditions that would make it unsafe to participate in the trial (e.g., clinically significant atrioventricular (AV) conduction disturbance, atrial flutter, atrial fibrillation, potentially life-threatening ventricular arrhythmias, decompensated valvular disease, presence of hemodynamically significant obstructive valvular disease, or cardiomyopathy)
• History of angioedema and/or organ damage from hypertension
• Serum potassium < 3.5 or > 5.5 mEq/L
• Any clinically significant laboratory value which in the investigator's judgment could be clinically significant to the outcome of this study.
• History of clinically important gastrointestinal resection or malabsorption
• Patient with a history or current evident of any condition, therapy, lab abnormality, or other circumstance that might confound the results of the study, or interfere with the patient's participation for the full duration of the study, such that it is not in the best interest of the patient to participate. (Including but not limited to: recent or current alcoholism, drug abuse within the prior 2 years, mental or legal incapacitation, any disease which could reasonably be expected to be fatal or life-threatening, or a history of malignancy ≤ 5 years prior to signing informed consent.)
• Currently participating or has participated in a study with an investigational compound or device within 30 days of signing informed consent.
• Inability to be taken off all current antihypertensive medication and placed on placebo for up to 12 weeks.
• Unwillingness or unlikely to adhere to the study procedures, keep appointments, or is planning to relocate during the study.
• Arm circumference great than 52 cm
• Smokers or former smokers who have quite less than 1 year prior to Visit 1
• Anemia (Hemoglobin < 11)
• Allergy to latex
• Deformed hands and/or fingers that would interfere with the collection of pulse volume amplitude measurements
• History of Raynaud's disease or any other vascular condition
• Bilateral mastectomy
• Aortic stenosis
• Patient is taking high doses of antioxidant supplements (vitamins, minerals, or other)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Brigham and Women's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Mark Alan Creager, MD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mark A Creager, MD

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Locations

CAVS Clinical Research Center

Little Rock, Arkansas, United States

VA San Diego Health Care System

San Diego, California, United States

University of Miami Diabetes Research Institute

Miami, Florida, United States

Indiana University School of Medicine

Indianapolis, Indiana, United States

Brigham and Women's Hospital Cardiovascular Division

Boston, Massachusetts, United States

St. Lukes Roosevelt Hospital

New York, New York, United States

University of Pennsylvania School of Medicine

Philadelphia, Pennsylvania, United States

University of Texas SW Medical Center at Dallas

Dallas, Texas, United States

Hypertension Clinical Pharmacology Baylor Clinic

Houston, Texas, United States

Countries

United States

References

Perlstein TS, Henry RR, Mather KJ, Rickels MR, Abate NI, Grundy SM, Mai Y, Albu JB, Marks JB, Pool JL, Creager MA. Effect of angiotensin receptor blockade on insulin sensitivity and endothelial function in abdominally obese hypertensive patients with impaired fasting glucose. Clin Sci (Lond). 2012 Feb;122(4):193-202. doi: 10.1042/CS20110284.

Reference Type: RESULT

PMID: 21861845 (View on PubMed)

Other Identifiers

2007-P-000490

Identifier Type: -

Identifier Source: org_study_id