- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT01766726
Effects of Newly-Initiated QUAD Therapy on Aortic/Coronary Inflammation in ART-Naïve Infected Patients (Quad)
15. marts 2017 opdateret af: Steven K. Grinspoon, MD, Massachusetts General Hospital
The main aims of this study are to determine whether: a) ART-naïve HIV+ subjects have increased artherosclerotic plaque inflammation/vulnerability, b) newly-initiated QUAD/Stribild therapy will decrease plaque inflammation/vulnerability in these subjects, and c) QUAD/Stribild therapy will improve indices of immune dysregulation and lipid dysfunction as a mechanism of improved plaque inflammation/vulnerability.
Parameters of lipid and immune function will also be assessed in healthy control subjects, for comparison.
Studieoversigt
Status
Afsluttet
Betingelser
Detaljeret beskrivelse
Patients with HIV are at higher risk of morbidity and mortality from cardiovascular disease than healthy subjects.
Antiretroviral therapy (ART) has greatly increased the lifespan of HIV+ patients, but their risk of CVD remains higher than normal.
Previously, it has been shown that compared to healthy control subjects, ART-treated HIV+ patients have more atherosclerotic plaque inflammation in the aorta.
This study is intended to determine whether atherosclerotic plaque inflammation/vulnerability is increased in ART-naïve HIV+ patients and whether these parameters can be improved through 6 months of newly-initiated QUAD/Stribild therapy.
Additionally, the study will determine whether indices of immune dysregulation and lipid dysfunction are increased in ART-naive HIV+ patients and whether these parameters can also be improved through 6 months of newly initiated QUAD/Stribild therapy.
Undersøgelsestype
Observationel
Tilmelding (Faktiske)
33
Kontakter og lokationer
Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.
Studiesteder
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Massachusetts
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Boston, Massachusetts, Forenede Stater, 02114
- Massachusetts General Hospital
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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 og ældre (Voksen, Ældre voksen)
Tager imod sunde frivillige
Ingen
Køn, der er berettiget til at studere
Alle
Prøveudtagningsmetode
Ikke-sandsynlighedsprøve
Studiebefolkning
Subjects with HIV infection being cared for in the Eastern Massachusetts area may be appprised of the study by their treating infectious disease doctors.
Additionally, subjects with HIV infection from the community will be recruited via posters, advertisements, e-postings.
Healthy control subjects from the community will be recruited via posters, advertisements, and e-postings.
Beskrivelse
HIV-infected Subjects:
Inclusion Criteria:
- men and women, ages 18+, with documented HIV-infection who are ART-naive and ready to be started on ART with QUAD/Stribild by their treating infectious disease doctors
Exclusion Criteria:
- history of prior, sustained ART use
- CD4 <50 or AIDS-defining illness
- known current opportunistic infection or acute infections (not including Hepatitis B/C)
- pregnancy or breastfeeding
- history of acute coronary syndrome or coronary artery stenting or surgery, diabetes mellitus, or significant autoimmune/inflammatory disease
- plans for sustained use during 6 month study interval of a confounding immune suppressant medication including intravenous or oral corticosteroid
- hemoglobin < 12.5 g/dl for men or < 12 g/dl for women
- eGFR < 70 ml/min/1.73 m2 calculated by CDK-EPI
- contrast dye allergy
- contraindication to beta blockers or nitroglycerin administered during MDCT coronary angiography (coronary CTA) protocol
- body weight > 320 lbs (PET scanner limitation)
- significant radiation exposure (>2 myocardial perfusion scans or CT angiograms) received within the past year
- reported active illicit drug use
Healthy control subjects:
Inclusion Criteria:
-men and women, ages 18+, without HIV infection
Exclusion Criteria:
- known current opportunistic infection or acute infections (not including Hepatitis B/C)
- pregnancy or breastfeeding
- history of acute coronary syndrome or coronary artery stenting or surgery, diabetes mellitus, or significant autoimmune/inflammatory disease
- sustained use of a confounding immune suppressant medication including intravenous or oral corticosteroid
- hemoglobin < 12.5 g/dl for men or < 12 g/dl for women
- reported active illicit drug use
Studieplan
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Observationsmodeller: Kohorte
- Tidsperspektiver: Fremadrettet
Kohorter og interventioner
Gruppe / kohorte |
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Healthy control subjects
Historical healthy control subjects matched to HIV+ patients on traditional cardiovascular risk factors will be studied at baseline with respect to arterial inflammation and coronary atherosclerotic plaque.
Prospectively recruited healthy control subjects matched to HIV+ patients on traditional cardiovascular risk factors will be studied at baseline with respect to lipid and immune function.
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ART-naïve HIV+ patients starting QUAD/Stribild
ART-naïve HIV+ patients who are about to be started QUAD/Stribild by their treating clinicians will be studied at baseline and 6 months after initiating QUAD/Stribild therapy.
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
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Aortic/coronary target to background ratio (TBR) on cardiac FDG-PET
Tidsramme: Baseline and change from baseline to 6 months in HIV cohort starting QUAD/Stribild
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Degree of aortic/coronary atherosclerotic plaque inflammation assessed via cardiac FDG-PET as target to background ratio (TBR) of the standardized uptake value (SUV).
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Baseline and change from baseline to 6 months in HIV cohort starting QUAD/Stribild
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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
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Aortic/coronary atherosclerotic plaque on coronary computed tomography angiography (coronary CTA)
Tidsramme: Baseline and change from baseline to 6 months in HIV cohort starting QUAD/Stribild
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Aortic/coronary atherosclerotic plaque assessed via coronary CTA.
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Baseline and change from baseline to 6 months in HIV cohort starting QUAD/Stribild
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Lipid and lipoprotein levels
Tidsramme: Baseline and change from baseline to 6 months in HIV cohort starting QUAD/Stribild
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Levels of lipids and lipoproteins including but not limited to levels of total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, and levels select apolipoprotein levels.
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Baseline and change from baseline to 6 months in HIV cohort starting QUAD/Stribild
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Indices of pro-atherogenic lipid dysfunction
Tidsramme: Baseline and change from baseline to 6 months in HIV cohort starting QUAD/Stribild
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Including HDL oxidative potential and other assessments of HDL function and structure.
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Baseline and change from baseline to 6 months in HIV cohort starting QUAD/Stribild
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Inflammatory biomarker levels
Tidsramme: Baseline and change from baseline to 6 months in HIV cohort starting QUAD/Stribild
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Levels of inflammatory biomarkers including but not limited to soluble CD163.
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Baseline and change from baseline to 6 months in HIV cohort starting QUAD/Stribild
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Percentage of circulating activated leukocyte subsets
Tidsramme: Baseline and change from baseline to 6 months in HIV cohort starting QUAD/Stribild
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Percentage of circulating activated leukocyte subsets including but not limited to percentage of circulating CD14+CD16+ monocytes assessed via flow cytometry.
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Baseline and change from baseline to 6 months in HIV cohort starting QUAD/Stribild
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Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Sponsor
Samarbejdspartnere
Efterforskere
- Ledende efterforsker: Steven K Grinspoon, MD, Massachusetts General Hospital
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.
Generelle publikationer
- Toribio M, Burdo TH, Fulda ES, Cetlin M, Chu SM, Feldpausch MN, Robbins GK, Neilan TG, Melbourne K, Grinspoon SK, Zanni MV. Effects of Integrase Inhibitor-Based ART on the NLRP3 Inflammasome Among ART-Naive People With HIV. Open Forum Infect Dis. 2020 Sep 29;7(10):ofaa459. doi: 10.1093/ofid/ofaa459. eCollection 2020 Oct.
- Toribio M, Park MH, Zanni MV, Robbins GK, Burdo TH, Williams KC, Feldpausch MN, Stone L, Melbourne K, Grinspoon SK, Fitzgerald ML. HDL Cholesterol Efflux Capacity in Newly Diagnosed HIV and Effects of Antiretroviral Therapy. J Clin Endocrinol Metab. 2017 Nov 1;102(11):4250-4259. doi: 10.1210/jc.2017-01334.
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. december 2012
Primær færdiggørelse (Faktiske)
1. januar 2016
Studieafslutning (Faktiske)
1. januar 2016
Datoer for studieregistrering
Først indsendt
9. januar 2013
Først indsendt, der opfyldte QC-kriterier
9. januar 2013
Først opslået (Skøn)
11. januar 2013
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
17. marts 2017
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
15. marts 2017
Sidst verificeret
1. marts 2017
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- 2012P001138
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 .
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