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

Obesity Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00675987
• Other study ID #: 2007-P-000490
• Status: Completed
• Phase: Phase 4
• Start date: May 2007
• Est. completion date: December 2008

Study information

• Verified date: August 2018
• Source: Brigham and Women's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 53
• Est. completion date: December 2008
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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)

Related Conditions & MeSH terms

• Hyperglycemia
• Hypertension
• Insulin Resistance
• Obesity

Intervention

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

Locations

Country	Name	City	State
United States	Brigham and Women's Hospital Cardiovascular Division	Boston	Massachusetts
United States	University of Texas SW Medical Center at Dallas	Dallas	Texas
United States	Hypertension Clinical Pharmacology Baylor Clinic	Houston	Texas
United States	Indiana University School of Medicine	Indianapolis	Indiana
United States	CAVS Clinical Research Center	Little Rock	Arkansas
United States	University of Miami Diabetes Research Institute	Miami	Florida
United States	St. Lukes Roosevelt Hospital	New York	New York
United States	University of Pennsylvania School of Medicine	Philadelphia	Pennsylvania
United States	VA San Diego Health Care System	San Diego	California

Sponsors (2)

Lead Sponsor	Collaborator
Brigham and Women's Hospital	Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 impa — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Insulin Sensitivity Utilizing the Euglycemic Hyperinsulinemic Clamp	Insulin clamp derived insulin sensitivity, as insulin stimulated glucose disposal corrected for steady state insulin level.	baseline, 8 weeks
Primary	Insulin Sensitivity Utilizing Endothelial Function as Assessed by Pulse Volume Amplitude	Endothelial function assessed as the ratio of pulse volume amplitude after compared with before a reactive hyperemia stimulus, measured by peripheral (fingertip) arterial tonometry. Reported values indicate the percentage change from Baseline in the ratio of pulse volume amplitude after compared to before the reactive hyperemia stimulus.	baseline, 8 weeks
Secondary	Change in Urine Albumin/Creatine	Urine was obtained to assess for the presence of microalbuminuria.	baseline, 8 weeks
Secondary	Change in hsCRP (High-sensitivity C-reactive Protein)	hsCRP (high-sensitivity C-reactive protein) is a marker of inflammation	baseline, 8 weeks
Secondary	Change in VCAM-1(Vascular Cell-adhesion Molecule-1)	VCAM-1 is an immunoglobulin-like adhesion molecule expressed on activated endothelial cells.	baseline, 8 weeks
Secondary	Change in MCP-1 (Monocyte Chemoattractant Protein-1)	MCP-1 is one of the key chemokines that regulate migration and infiltration of monocytes/macrophages.	baseline, 8 weeks
Secondary	Change in Ox-LDL (Oxidized Low-density Lipoprotein)	ox-LDL measures protein damage due to the oxidative modification of the ApoB subunit on LDL cholesterol.	baseline, 8 weeks
Secondary	Change in F2-isoprostanes	F2-isoprostanes is a marker of oxidative stress.	baseline, 8 weeks
Secondary	Change in E-selectin	E-selectin is expressed on inflamed endothelial cells in response to treatment with inflammatory cytokines.	baseline, 8 weeks