A Randomized Clinical Trial To Study Losartan On Endothelial Dysfunction and Insulin Resistance In Obese Patients
9. august 2018 oppdatert av: 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.
Studieoversikt
Status
Fullført
Forhold
Intervensjon / Behandling
Studietype
Intervensjonell
Registrering (Faktiske)
53
Fase
- Fase 4
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiesteder
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Arkansas
-
Little Rock, Arkansas, Forente stater, 72205
- CAVS Clinical Research Center
-
-
California
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San Diego, California, Forente stater, 92161
- VA San Diego Health Care System
-
-
Florida
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Miami, Florida, Forente stater, 33136
- University of Miami Diabetes Research Institute
-
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Indiana
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Indianapolis, Indiana, Forente stater, 46202
- Indiana University School of Medicine
-
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Massachusetts
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Boston, Massachusetts, Forente stater, 02115
- Brigham and Women's Hospital Cardiovascular Division
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New York
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New York, New York, Forente stater, 10025
- St. Lukes Roosevelt Hospital
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Pennsylvania
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Philadelphia, Pennsylvania, Forente stater, 19104
- University of Pennsylvania School of Medicine
-
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Texas
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Dallas, Texas, Forente stater, 75390
- University of Texas SW Medical Center at Dallas
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Houston, Texas, Forente stater, 77030
- Hypertension Clinical Pharmacology Baylor Clinic
-
-
Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
18 år til 75 år (Voksen, Eldre voksen)
Tar imot friske frivillige
Nei
Kjønn som er kvalifisert for studier
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
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Annen
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Firemannsrom
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Aktiv komparator: Losartan
Losartan 100 mg 1 tab po QD
|
losartan 100 mg tablets 1 tab po QD
Andre navn:
|
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Placebo komparator: Placebo
Placebo 1 tab po QD
|
Placebo 1 po QD
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
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 |
Tiltaksbeskrivelse |
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
|
Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Sponsor
Samarbeidspartnere
Publikasjoner og nyttige lenker
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Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart
1. mai 2007
Primær fullføring (Faktiske)
1. desember 2008
Studiet fullført (Faktiske)
1. desember 2008
Datoer for studieregistrering
Først innsendt
8. mai 2008
Først innsendt som oppfylte QC-kriteriene
9. mai 2008
Først lagt ut (Anslag)
12. mai 2008
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
6. september 2018
Siste oppdatering sendt inn som oppfylte QC-kriteriene
9. august 2018
Sist bekreftet
1. august 2018
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- 2007-P-000490
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