Denne side blev automatisk oversat, og nøjagtigheden af ​​oversættelsen er ikke garanteret. Der henvises til engelsk version for en kildetekst.

Effects of Febuxostat on Adipokines and Kidney Disease in Diabetic Chronic Kidney Disease

9. august 2016 opdateret af: Srinvasan Beddhu, University of Utah

Hyperuricemia is emerging as a risk factor for development of diabetes and metabolic syndrome. Recently, it was shown in in-vitro cell culture experiments that hyperuricemia induces redox-dependent signaling and oxidative stress in adipocytes. By targeting levels of uric acid with febuxostat it is hypothesized that the levels of oxidative stress in adipose tissue (obtained by fat biopsy) will decrease.

Primary aims of the study are to determine whether febuxostat therapy in overweight or obese, diabetic patients with stage 3 Chronic Kidney Disease (CKD) and high serum uric acid levels

  1. will affect adipose tissue concentrations of thiobarbituric acid reactive substance (TBARS), a marker of oxidative stress
  2. will affect adipose tissue expression and concentrations of adiponectin; and
  3. will affect urinary concentrations of transforming growth factor (TGF)- B1.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

Hyperuricemia is highly prevalent in the US population and commonly clusters with obesity and metabolic syndrome. It remains controversial whether this reflects an epiphenomenon or connotes a causal role of hyperuricemia in metabolic syndrome. If indeed hyperuricemia plays a causal role in metabolic syndrome, it would be expected that hyperuricemia will impact on the molecular signals that mediate the effects of adiposity on inflammation and insulin resistance.

Adipokines, the protein hormones produced by the adipocytes, serve as the signals for the effects of adipocytes on insulin resistance, dyslipidemia, hypertension, inflammation and atherosclerosis. Adipokines include tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), plasminogen activator inhibitor (PAI-1), leptin, angiotensinogen and adiponectin. In obesity, the production of TNF-α, IL-6, PAI-1, leptin and angiotensinogen increases whereas the production of adiponectin decreases. Increased expression of pro-inflammatory TNF-α and IL-6 and decreased expression of anti-inflammatory adiponectin by adipocytes results in insulin resistance and inflammation.

As oxidative stress in adipose tissue is considered to play a critical role in dysregulation of adipokines production in obesity and that hyperuricemia induces oxidative stress in adipocytes, it is hypothesized that hyperuricemia alters adipose tissue production of adipokines; therefore, febuxostat therapy will decrease hyperuricemia and thereby, have beneficial effects on adipokine production by adipose tissue; the favorable effects on adipokine production by febuxostat therapy will result in decrease in plasma levels of markers of inflammation; and as a result of the above, urinary markers of kidney disease will improve.

Chronic Kidney Disease (CKD) patients with type 2 diabetes will be studies because this population has a high prevalence of hyperuricemia and likely represents a target population which might benefit from reduction of uric acid levels.

This is a placebo-controlled, double-blinded, randomized controlled trial to examine the effects of uric acid lowering with oral febuxostat on adipokines and markers of inflammation.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

80

Fase

  • Ikke anvendelig

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

  • Forenede Stater
    • Utah
      • Salt Lake City, Utah, Forenede Stater, 84112
        • University of Utah

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

Beskrivelse

Inclusion Criteria:

  • Age > 18 years
  • BMI > 25 kg/m2
  • type 2 diabetes
  • serum uric acid ≥ 5.5 mg/dl in men and ≥ 4.6 mg/dl in women
  • eGFR 30-60 mL/min/1.73m2

Exclusion Criteria:

  • History of gout
  • concurrent use of azathioprine, mercaptopurine, theophylline, allopurinol, thiazolidinediones or warfarin
  • concurrent use of metformin
  • current antibiotic therapy
  • pregnant women
  • prisoners

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Firedobbelt

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Aktiv komparator: Febuxostat
80 mg/day of febuxostat for 24 weeks
Medicin: Febuxostat
80 mg/day of febuxostat for 24 weeks
Andre navne:
  • Uloric
Placebo komparator: Placebo
1 placebo tablet per day for 24 weeks
Medicin: Placebo
1 placebo tablet per day for 24 weeks

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Change in Thiobarbituric Acid Reactive Substance (TBARS) Concentration in Adipose Tissue From Baseline to 24 Weeks
Tidsramme: Baseline and 24 weeks
The percent difference in thiobarbituric acid reactive substance (TBARS) concentration geometric mean values from baseline to 24 weeks was calculated for each arm
Baseline and 24 weeks
Change in Adiponectin Concentration in Adipose Tissue From Baseline to 24 Weeks
Tidsramme: Baseline and 24 weeks
The percent difference in adiponectin concentration geometric mean values from baseline to 24 weeks was calculated for each arm
Baseline and 24 weeks
Change in Urinary Concentrations of Transforming Growth Factor-beta1 (TGF-beta1) From Baseline to 24 Weeks
Tidsramme: Baseline and 24 weeks
The percent difference in TGF-beta1 concentration geometric mean values from baseline to 24 weeks was calculated for each arm
Baseline and 24 weeks

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Change in Tumor Necrosis Factor-α (TNF-α) Concentration in Plasma From Baseline to 24 Weeks
Tidsramme: Baseline and 24 weeks
The percent difference in plasma TNF-α concentration geometric mean values from baseline to 24 weeks was calculated for each arm
Baseline and 24 weeks
Change in Interleukin-6 (IL-6) Concentration in Plasma From Baseline to 24 Weeks
Tidsramme: Baseline and 24 weeks
The percent difference in plasma IL-6 concentration geometric mean values from baseline to 24 weeks was calculated for each arm
Baseline and 24 weeks
Change in High Sensitivity C-Reactive Protein (hsCRP) Concentration in Plasma From Baseline to 24 Weeks
Tidsramme: Baseline and 24 weeks
The percent difference in plasma hsCRP concentration geometric mean values from baseline to 24 weeks was calculated for each arm
Baseline and 24 weeks

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

University of Utah

Samarbejdspartnere

Takeda

Efterforskere

  • Ledende efterforsker: Srinivasan Beddhu, MD, University of Utah

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

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 2011

Primær færdiggørelse (Faktiske)

1. oktober 2013

Studieafslutning (Faktiske)

1. december 2013

Datoer for studieregistrering

Først indsendt

20. april 2011

Først indsendt, der opfyldte QC-kriterier

6. maj 2011

Først opslået (Skøn)

9. maj 2011

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Skøn)

3. oktober 2016

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

9. august 2016

Sidst verificeret

1. august 2016

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • IRB_00044016

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 .

Abonner