A Randomized Clinical Trial To Study Losartan On Endothelial Dysfunction and Insulin Resistance In Obese Patients
9. august 2018 opdateret af: Mark Alan Creager, MD, Brigham and Women's Hospital
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.
Studieoversigt
Status
Afsluttet
Betingelser
Intervention / Behandling
Undersøgelsestype
Interventionel
Tilmelding (Faktiske)
53
Fase
- Fase 4
Kontakter og lokationer
Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.
Studiesteder
-
-
Arkansas
-
Little Rock, Arkansas, Forenede Stater, 72205
- CAVS Clinical Research Center
-
-
California
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San Diego, California, Forenede Stater, 92161
- VA San Diego Health Care System
-
-
Florida
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Miami, Florida, Forenede Stater, 33136
- University of Miami Diabetes Research Institute
-
-
Indiana
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Indianapolis, Indiana, Forenede Stater, 46202
- Indiana University School of Medicine
-
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Massachusetts
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Boston, Massachusetts, Forenede Stater, 02115
- Brigham and Women's Hospital Cardiovascular Division
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New York
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New York, New York, Forenede Stater, 10025
- St. Lukes Roosevelt Hospital
-
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Pennsylvania
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Philadelphia, Pennsylvania, Forenede Stater, 19104
- University of Pennsylvania School of Medicine
-
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Texas
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Dallas, Texas, Forenede Stater, 75390
- University of Texas SW Medical Center at Dallas
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Houston, Texas, Forenede Stater, 77030
- Hypertension Clinical Pharmacology Baylor Clinic
-
-
Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
18 år til 75 år (Voksen, Ældre voksen)
Tager imod sunde frivillige
Ingen
Køn, der er berettiget til at studere
Alle
Beskrivelse
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)
Studieplan
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Andet
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Firedobbelt
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
|
Aktiv komparator: Losartan
Losartan 100 mg 1 tab po QD
|
losartan 100 mg tablets 1 tab po QD
Andre navne:
|
|
Placebo komparator: Placebo
Placebo 1 tab po QD
|
Placebo 1 po QD
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Insulin Sensitivity Utilizing the Euglycemic Hyperinsulinemic Clamp
Tidsramme: baseline, 8 weeks
|
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
Tidsramme: baseline, 8 weeks
|
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
|
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Change in Urine Albumin/Creatine
Tidsramme: baseline, 8 weeks
|
Urine was obtained to assess for the presence of microalbuminuria.
|
baseline, 8 weeks
|
|
Change in hsCRP (High-sensitivity C-reactive Protein)
Tidsramme: baseline, 8 weeks
|
hsCRP (high-sensitivity C-reactive protein) is a marker of inflammation
|
baseline, 8 weeks
|
|
Change in VCAM-1(Vascular Cell-adhesion Molecule-1)
Tidsramme: baseline, 8 weeks
|
VCAM-1 is an immunoglobulin-like adhesion molecule expressed on activated endothelial cells.
|
baseline, 8 weeks
|
|
Change in MCP-1 (Monocyte Chemoattractant Protein-1)
Tidsramme: baseline, 8 weeks
|
MCP-1 is one of the key chemokines that regulate migration and infiltration of monocytes/macrophages.
|
baseline, 8 weeks
|
|
Change in Ox-LDL (Oxidized Low-density Lipoprotein)
Tidsramme: baseline, 8 weeks
|
ox-LDL measures protein damage due to the oxidative modification of the ApoB subunit on LDL cholesterol.
|
baseline, 8 weeks
|
|
Change in F2-isoprostanes
Tidsramme: baseline, 8 weeks
|
F2-isoprostanes is a marker of oxidative stress.
|
baseline, 8 weeks
|
|
Change in E-selectin
Tidsramme: baseline, 8 weeks
|
E-selectin is expressed on inflamed endothelial cells in response to treatment with inflammatory cytokines.
|
baseline, 8 weeks
|
Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Sponsor
Samarbejdspartnere
Publikationer og nyttige links
Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.
Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart
1. maj 2007
Primær færdiggørelse (Faktiske)
1. december 2008
Studieafslutning (Faktiske)
1. december 2008
Datoer for studieregistrering
Først indsendt
8. maj 2008
Først indsendt, der opfyldte QC-kriterier
9. maj 2008
Først opslået (Skøn)
12. maj 2008
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
6. september 2018
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
9. august 2018
Sidst verificeret
1. august 2018
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- 2007-P-000490
Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .