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

This study is currently recruiting participants.
Verified by Brigham and Women's Hospital, May 2008

Sponsors and Collaborators: Brigham and Women's Hospital
Merck
Information provided by: Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT00675987
  Purpose

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.


Condition Intervention Phase
Obesity
Hypertension
Impaired Fasting Glucose
Drug: losartan
Drug: Placebo control
Phase IV

MedlinePlus related topics:   High Blood Pressure    Obesity   

Drug Information available for:   Insulin    Dextrose    Losartan    Losartan potassium    Potassium chloride   

U.S. FDA Resources

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

Further study details as provided by Brigham and Women's Hospital:

Primary Outcome 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 ] [ Designated as safety issue: No ]

Secondary Outcome 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 ] [ Designated as safety issue: No ]

Estimated Enrollment:   150
Study Start Date:   May 2007
Estimated Study Completion Date:   July 2008
Estimated Primary Completion Date:   July 2008 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
1: Active Comparator
Losartan 100 mg 1 tab po QD
Drug: losartan
losartan 100 mg tablets 1 tab po QD
2: Placebo Comparator
Placebo 1 tab po QD
Drug: Placebo control
Placebo 1 po QD

  Eligibility
Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Criteria

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)
  Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00675987

Locations
United States, Arkansas
CAVS Clinical Research Center     Recruiting
      Little Rock, Arkansas, United States, 72205
      Contact: Angie Smither     501-257-5882     smithangelaa@uams.edu    
      Principal Investigator: Neda Rasouli, MD            
United States, California
VA San Diego Health Care System     Recruiting
      San Diego, California, United States, 92161
      Contact: Adrienne Armstrong     858-552-8585 ext 2884     adriennearmstrong@sbcglobal.net    
      Principal Investigator: Robert Henry, MD            
United States, Florida
University of Miami Diabetes Research Institute     Recruiting
      Miami, Florida, United States, 33136
      Contact: Robert Agramonte     305-243-6573     ragramon@med.miami.edu    
      Principal Investigator: Jennifer Marks, MD            
United States, Indiana
Indiana University School of Medicine     Recruiting
      Indianapolis, Indiana, United States, 46202
      Contact: Robin Chisolm     317-274-7679     rlchiso@iupui.edu    
      Principal Investigator: Kieren Mather, MD            
United States, Massachusetts
Brigham and Women's Hospital Cardiovascular Division     Recruiting
      Boston, Massachusetts, United States, 02115
      Contact: Jeanne Doyle, BS, RN, BC     617-525-7055     jdoyle7@partners.org    
      Contact: Nicole Navarrete     617-525-7055     nnavarrete@partners.org    
      Principal Investigator: Mark A Creagear, MD            
United States, New York
St. Lukes Roosevelt Hospital     Recruiting
      New York, New York, United States, 10025
      Contact: Sylvaine Frances     212-523-4572     sfrancis@chpnet.org    
      Principal Investigator: Jeannine Albu, MD            
United States, Pennsylvania
University of Pennsylvania School of Medicine     Recruiting
      Philadelphia, Pennsylvania, United States, 19104
      Contact: Carissa Fuller     215-746-2084     Carissa.Fuller@uphs.upenn.edu    
      Principal Investigator: Michael Rickels, MD            
United States, Texas
University of Texas SW Medical Center at Dallas     Recruiting
      Dallas, Texas, United States, 75390
      Contact: Thanalakshmi Seenivasan     214-648-9705     Thanalakshmi.Seenivasan@UTSouthwestern.edu    
      Principal Investigator: Scott Grundy, MD            
Hypertension Clinical Pharmacology Baylor Clinic     Recruiting
      Houston, Texas, United States, 77030
      Contact: Charlyne Wright     713-798-2375     cwright@bcm.tmc.edu    
      Principal Investigator: James Pool, MD            

Sponsors and Collaborators
Brigham and Women's Hospital
Merck

Investigators
Principal Investigator:     Mark A Creager, MD     Brigham and Women's Hospital    
  More Information


Responsible Party:   Brigham and Women's Hospital ( Mark A. Creager, MD )
Study ID Numbers:   2007-P-000490
First Received:   May 8, 2008
Last Updated:   May 9, 2008
ClinicalTrials.gov Identifier:   NCT00675987
Health Authority:   United States: Institutional Review Board

Keywords provided by Brigham and Women's Hospital:
Impaired Fasting Glucose FPG >100-<126 mg/dL  

Study placed in the following topic categories:
Obesity
Losartan
Metabolic Diseases
Vascular Diseases
Overweight
Angiotensin II
Insulin
Body Weight
Hyperinsulinism
Signs and Symptoms
Nutrition Disorders
Overnutrition
Insulin Resistance
Glucose Metabolism Disorders
Metabolic disorder
Hypertension

Additional relevant MeSH terms:
Angiotensin II Type 1 Receptor Blockers
Molecular Mechanisms of Pharmacological Action
Therapeutic Uses
Cardiovascular Diseases
Cardiovascular Agents
Anti-Arrhythmia Agents
Antihypertensive Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 23, 2008




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