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

NCT00675987 | Completed Phase 4 Results

• 1 other identifier: 2007-P-000490
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 9

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

Keywords

Impaired Fasting Glucose FPG >100-<126 mg/dL

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (7)

• Change in Urine Albumin/Creatine

  baseline, 8 weeks

• Change in hsCRP (High-sensitivity C-reactive Protein)

  baseline, 8 weeks

• Change in VCAM-1(Vascular Cell-adhesion Molecule-1)

  baseline, 8 weeks

• Change in MCP-1 (Monocyte Chemoattractant Protein-1)

  baseline, 8 weeks

• Change in Ox-LDL (Oxidized Low-density Lipoprotein)

  baseline, 8 weeks

Study Arms (2)

Losartan

ACTIVE COMPARATOR

Losartan 100 mg 1 tab po QD

Drug: losartan

Placebo

PLACEBO COMPARATOR

Placebo 1 tab po QD

Drug: Placebo control

Interventions

losartan DRUG

losartan 100 mg tablets 1 tab po QD

Also known as: Cozaar

Losartan

Placebo control DRUG

Placebo 1 po QD

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (9)

CAVS Clinical Research Center

Little Rock, Arkansas, 72205, United States

Location

VA San Diego Health Care System

San Diego, California, 92161, United States

Location

University of Miami Diabetes Research Institute

Miami, Florida, 33136, United States

Location

Indiana University School of Medicine

Indianapolis, Indiana, 46202, United States

Location

Brigham and Women's Hospital Cardiovascular Division

Boston, Massachusetts, 02115, United States

Location

St. Lukes Roosevelt Hospital

New York, New York, 10025, United States

Location

University of Pennsylvania School of Medicine

Philadelphia, Pennsylvania, 19104, United States

Location

University of Texas SW Medical Center at Dallas

Dallas, Texas, 75390, United States

Location

Hypertension Clinical Pharmacology Baylor Clinic

Houston, Texas, 77030, United States

Location

Related 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 impaired fasting glucose. Clin Sci (Lond). 2012 Feb;122(4):193-202. doi: 10.1042/CS20110284.

  PMID: 21861845 RESULT

MeSH Terms

Conditions

Obesity; Hypertension; Hyperglycemia

Interventions

Losartan

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Vascular Diseases; Cardiovascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrazoles

Results Point of Contact

• Title: Mark A. Creager, MD
• Organization: Brigham and Women's Hospital

mcreager@partners.org

617-732-5267

Study Officials

• Mark A Creager, MD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 8, 2008
• First Posted: May 12, 2008
• Study Start: May 1, 2007
• Primary Completion: December 1, 2008
• Study Completion: December 1, 2008
• Last Updated: September 6, 2018
• Results First Posted: August 21, 2012

Record last verified: 2018-08

Locations

US (9)