Official Title: “Protocol Merck 318-00: A Double-Blind, Placebo-Controlled, Randomized, Parallel, Clinical Trial To Study The Effect Of Losartan Potassium On Endothelial Dysfunction And Insulin Resistance In Obese Patients With Impaired Fasting Glucose”

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.

Study Type: Interventional

Study Design: Other, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study

Study Primary Completion Date: December 2008

Intervention(s) in this Clinical Trial

• Drug: losartan
  • losartan 100 mg tablets 1 tab po QD
• Drug: Placebo control
  • Placebo 1 po QD

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • Losartan 100 mg 1 tab po QD
• Placebo Comparator: 2
  • Placebo 1 tab po QD

Primary Measures

• Assess the effect of Losartan 100mg on insulin sensitivity utilizing the euglycemic hyperinsulinemic clamp and the effect on endothelial function as assessed by pulse volume amplitude measured by change from baseline after 8 weeks of treatment
  • Time Frame: 8 weeks
    Safety Issue?: No

Secondary Measures

• To evaluate the change from baseline cytokines, markers of inflammation, and markers of oxidative stress after 8 weeks of treatment. Also to evaluate the effect on microalbuminuria after 8 weeks of treatment.
  • Time Frame: 8 weeks
    Safety Issue?: No

Inclusion Criteria:

• Currently taking 1 or no antihypertensive medication
• Male and female between 18 and 75 years of age
• Mean trough SiDBP ≥80 and < 100 mm Hg
• Mean trough SiSBP ≥120 and <160 mm Hg
• Non-diabetic patients with fasting plasma glucose ≥100 mg/dL and <126 mg/dL
• 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 (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 MI, PCI, CABG, CHF, unstable angina, TIA, or CVA
• Concomitant cardiac conditions that would make it unsafe to participate in the trial (e.g., clinically significant 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)

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 75 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Brigham and Women's Hospital

Overall Clinical Trial Officials and Contacts

Mark A Creager, MD Principal Investigator Brigham and Women's Hospital  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00675987

Study ID Number: 2007-P-000490

ClinicalTrials.gov Identifier: NCT00675987

Health Authority: United States: Institutional Review Board