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

Modulation of Human Myocardial Metabolism by GLP-1 Dose Response

19. januar 2016 opdateret af: Indiana University

The objective of this proposal is to provide quantitative dose-response data for effects of GLP-1 on myocardial glucose uptake in healthy control subjects and obese type 2 diabetic subjects, in support of the design of later studies evaluating therapeutic applications of GLP-1 to heart disease.

Aim 1: To measure the effects of GLP-1 infusion on myocardial fuel selection in lean healthy humans under fasting (fatty acid-dominant) conditions. Four groups of 10 lean healthy subjects will be studied during infusions of 0 (saline control), 0.5, 1.5, and 4.0 pmol/kg/min GLP-1 (one study per subject). Cardiac metabolism will be measured using PET, using a dual-tracer approach which allows measurement of myocardial glucose uptake (the primary endpoint) along with total oxidation rate and myocardial perfusion (secondary endpoints). In concert with measures of circulating metabolites and regulatory hormones, the investigators will produce the most comprehensive assessment of actions of GLP-1 on myocardial metabolism in humans to date. Effects of each dose will be compared to the saline control, plus the investigators will combine all data and use nonlinear curve-fitting to derive sensitivity (ED50) and maximal responses for GLP-1 effects on myocardial glucose uptake.

Aim 2: To measure the effects of GLP-1 infusion on myocardial fuel selection in obese type 2 diabetic humans under fasting (fatty acid-dominant) conditions Four groups of 10 obese type 2 diabetic subjects will be studied during infusions of 0, 0.5, 1.5, and 4.0 pmol/kg/min GLP-1 as under Aim 1. Analyses will be parallel to those described under Aim 1. Results from Aims 1 and 2 will be combined to allow direct comparison of the dose-response between nondiabetic control and type 2 diabetic subjects.

No literature has been published to inform dose selection in the design of clinical trials of GLP-1 for modulation of heart fuel selection. With our expertise and experience in PET measurement of heart metabolism in diabetes, the investigators are uniquely positioned to fill this gap in knowledge. These studies are a necessary preamble to further evaluation of the potential for GLP-1 based treatments in heart disease.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

33

Fase

  • Fase 2
  • Fase 3

Kontakter og lokationer

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

Studiesteder

  • Forenede Stater
    • Indiana
      • Indianapolis, Indiana, Forenede Stater, 46202
        • Indiana Clinical Research Center

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 60 år (Voksen)

Tager imod sunde frivillige

Ja

Køn, der er berettiget til at studere

Alle

Beskrivelse

Inclusion Criteria:

  • Age 18-60
  • Lean subjects will be defined as having a BMI <25 kg/m2, in good general health, taking no regular medications
  • Diabetic subjects will be obese (BMI >30 kg/m2 but <40 kg/m2), HbA1c 7.0-10.0%, treated with diet and exercise plus oral agents or injected insulin. All diabetic subjects will be treated with injected insulin for 2 weeks prior to study, to avoid potential confounding effects of other antidiabetic agents.

Exclusion Criteria:

  • Chronic illnesses or infections (other than type 2 diabetes)
  • Known coronary artery disease or abnormal ECG on screening evaluation
  • Blood pressure > 160/100 mmHg on two occasions during screening evaluations. Current use of 3 or fewer blood pressure medications with blood pressure below this cutpoint will be acceptable.
  • Total cholesterol > 240 mg/dL. Current use of 2 or fewer lipid lowering agents with cholesterol below this cutpoint will be acceptable.
  • Diabetic subjects: Treatment with a GLP-1 agonist or DPP4 inhibitor within the past 6 months
  • Known intolerance to injected GLP-1 agonist
  • Treatment with PPAR gamma agonists currently or within the past 6 months
  • Recognized microvascular complications (retinopathy, nephropathy, neuropathy)
  • Unwillingness or inability to use injected insulin for the purposes of this study
  • Chronic pain or other physical conditions which limit ability to remain supine for the duration of the study protocol
  • History of claustrophobia, musculoskeletal or other factors which would result in an inability to comfortably remain within PET scanner gantry for the duration of the imaging protocol
  • Occupational, investigational or other known radiation exposure which, together with the planned radiologic studies, will result in greater than 500 mrem total exposure in a contiguous 12 month period
  • For female participants, current pregnancy

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: Ikke-randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Enkelt

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Andet: Saline
12 hour saline (control) infusion prior to PET study
Medicin: Saline
Normal saline placebo infusion for 12 hours prior to PET study
Andre navne:
  • Normal saltvand
Eksperimentel: GLP-1 Low dose
GLP-1 Low Dose: 0.5 pmol/kg/min for 12 hours prior to PET study
Medicin: GLP-1 Low Dose
0.5mmol/kg/hr GLP-1 for 12 hours prior to PET study
Eksperimentel: GLP-1 Mid-Range Dose
GLP-1 Mid-Range Dose: 1.5 pmol/kg/min for 12 hours prior to PET study
Medicin: GLP-1 Mid-Range Dose
1.5mmol/kg/min for 12 hours prior to PET study
Eksperimentel: GLP-1 High Dose
GLP-1 High Dose: 4.0 pmol/kg/min for 12 hours prior to PET study
Medicin: GLP-1 High Dose
4.0mmol/kg/min GLP-1 for 12 hours prior to PET study

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Myocardial Glucose Uptake.
Tidsramme: After 12 hours of glucagon-like peptide 1 (GLP-1) exposure
Myocardial glucose uptake measured using 18FDG PET, quantified using a 3-compartment model with a lumped constant of 1.0.
After 12 hours of glucagon-like peptide 1 (GLP-1) exposure

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Myocardial Blood Flow
Tidsramme: After 12 hours of GLP-1 exposure
Myocardial perfusion derived from acetate kinetics
After 12 hours of GLP-1 exposure
Myocardial Total Oxidation Rate
Tidsramme: After 12 hours of GLP-1 exposure
MVO2 derived from acetate kinetics
After 12 hours of GLP-1 exposure
Cardiac Index
Tidsramme: After 12 hours of GLP-1 exposure
Impedance cardiography-derived measurement of cardiac index, assessed following 12 hour exposure to treatment condition concurrent with the PET measurements.
After 12 hours of GLP-1 exposure
GLP-1 Concentrations
Tidsramme: After 12 hours of GLP-1 exposure
Achieved GLP-1 concentrations at the end of the 12 hour treatment exposure
After 12 hours of GLP-1 exposure

Samarbejdspartnere og efterforskere

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

Sponsor

Indiana University

Samarbejdspartnere

National Heart, Lung, and Blood Institute (NHLBI)

Efterforskere

  • Ledende efterforsker: Kieren J Mather, MD, Indiana University

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 2010

Primær færdiggørelse (Faktiske)

1. december 2012

Studieafslutning (Faktiske)

1. december 2012

Datoer for studieregistrering

Først indsendt

21. maj 2012

Først indsendt, der opfyldte QC-kriterier

24. maj 2012

Først opslået (Skøn)

30. maj 2012

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Skøn)

17. februar 2016

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

19. januar 2016

Sidst verificeret

1. januar 2016

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • 1010002497
  • R21HL092799 (U.S. NIH-bevilling/kontrakt)

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 .

Kliniske forsøg med Saline

Søg i lignende forsøg

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

CROs by country

CROs in Mauritius

Betingelser

Sjældne sygdomme

Narkotikainterventioner

Kosttilskud

Sponsor / samarbejdspartnere

Placeringer

Abonner