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Effect of Bile Acid Sequestration on Postprandial GLP-1 Secretion, Glucose Homeostasis and Gut Microbiota

20. november 2015 opdateret af: Andreas Brønden, University Hospital, Gentofte, Copenhagen

Accumulating evidence suggests that bile acids and bacteria in our intestines may constitute essential components in the complex mechanisms regulating gut hormone secretion and glucose homeostasis. At the same time, bile acids and gut bacteria are interdependent. Thus, it is likely that modification of the enterohepatic circulation of bile acids can lead to changes in gut hormone secretion or gut bacteria composition and consequently affect glucose homeostasis.

The current study is a human interventional study with 7-day ingestion of a bile acid sequestrant or placebo, preceded and followed by meal tests and faecal sampling. The aim is to examine how (and if) bile acid sequestration can influence postprandial glucagon-like peptide-1 (GLP-1) secretion, gut microbiota and glucose homeostasis in patients with type 2 diabetes and healthy individuals. As a tool to sequester bile acids we will use sevelamer, a phosphate binding resin used in the treatment of hyperphosphataemia in adult patients with chronic kidney disease. Surprisingly, sevelamer was recently shown to improve glycaemic control in patients with chronic kidney disease and type 2 diabetes.

The investigators hypothesize that higher luminal concentrations of bile acids in the distal gut will elicit changes in the postprandial gut hormone secretion and gut bacteria composition. The current study will help to clarify this hypothesis and improve our general understanding of the association between bile acid circulation and signalling, gut hormone secretion, gut bacteria and glucose metabolism.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

50

Fase

  • Ikke anvendelig

Kontakter og lokationer

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

Studiesteder

  • Danmark
      • Hellerup, Danmark, 2900
        • Diabetes Research Division, Gentofte Hospital, Copenhagen

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

35 år til 80 år (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ja

Køn, der er berettiget til at studere

Alle

Beskrivelse

Inclusion Criteria:

Both groups

  • Caucasian ethnicity
  • Normal haemoglobin
  • Age above 35 years and below 80 years
  • Informed and written consent
  • BMI > 23 kg/m2 and <35 kg/m2

Patients with type 2 diabetes

  • Type 2 diabetes for at least 3 months
  • Diagnosed according to the criteria of the World Health Organization (WHO)

Healthy Subjects

  • Normal fasting plasma glucose (FPG) <6.5 mM and
  • Normal glycated haemoglobin (HbA1c) <6.0 %

Exclusion Criteria:

Both groups

  • Liver disease (alanine aminotransferase (ALAT) and/or serum aspartate aminotransferase (ASAT) >2 times normal values) or history of hepatobiliary disorder
  • Gastrointestinal disease, previous intestinal resection, cholecystectomy or any major intra-abdominal surgery
  • Hypo- or hyperphosphataemia
  • Nephropathy (serum creatinine >150 µM and/or albuminuria
  • Treatment with medicine that cannot be paused for 12 hours
  • Intake of antibiotics six months prior to study
  • Hypo- or hypercalcaemia
  • Hypo- and hyperthyroidism
  • Treatment with oral anticoagulants
  • Active or recent malignant disease
  • Any treatment or condition requiring acute or sub-acute medical or surgical intervention
  • Lack of effective birth control in premenopausal women
  • Positive pregnancy test on study days in premenopausal women
  • Tobacco smoking
  • Any condition considered incompatible with participation by the investigators

Patients with type 2 diabetes

  • Treatment with insulin
  • Treatment with incretin-based therapy

Healthy Subjects

  • Diabetes or
  • prediabetes (fasting plasma glucose levels >6.5 mM or HbA1c >6.0%)
  • First-degree relatives with diabetes

Studieplan

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

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Grundvidenskab
  • Tildeling: Randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Dobbelt

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Aktiv komparator: T2DM, sevelamer
Patients with type 2 diabetes treated with sevelamer
Medicin: Sevelamer 1600 mg TID for 7 days
Placebo komparator: T2DM, placebo
Patients with type 2 diabetes treated with placebo
Medicin: Placebo 1600 mg TID for 7 days
Aktiv komparator: Healthy subjects, sevelamer
Healthy subjects treated with sevelamer
Medicin: Sevelamer 1600 mg TID for 7 days
Placebo komparator: Healthy subjects, placebo
Healthy subjects treated with placebo
Medicin: Placebo 1600 mg TID for 7 days

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Incremental and total area under the Concentration-Time Curve (AUC 0-240 min)
Tidsramme: -30, -15, 0, 10, 20, 30, 45, 60, 90, 120, 180, 240 min on study days 1 and 7 (meal tests start at 0 min)
Postprandial responses of glucagon-like peptide-1 (GLP-1)
-30, -15, 0, 10, 20, 30, 45, 60, 90, 120, 180, 240 min on study days 1 and 7 (meal tests start at 0 min)

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Incremental and total area under the Concentration-Time Curve (AUC 0-240 min)
Tidsramme: -30, -15, 0, 10, 20, 30, 45, 60, 90, 120, 180, 240 min on study days 1 and 7 (meal tests start at 0 min)
Postprandial responses of various other gut hormones
-30, -15, 0, 10, 20, 30, 45, 60, 90, 120, 180, 240 min on study days 1 and 7 (meal tests start at 0 min)

Andre resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Blood analysis
Tidsramme: Fasting status on study days 1 and 7
Lipids
Fasting status on study days 1 and 7
Blood analysis
Tidsramme: Fasting status on study days 1 and 7
Inflammatory and metabolic markers
Fasting status on study days 1 and 7
Faecal samples
Tidsramme: Prior to study days 1 and 7
Gut microbiota composition
Prior to study days 1 and 7
Blood analysis of paracetamol
Tidsramme: -30 min to 240 min (ingestion of meal at 0 min) on study days 1 and 7
Assessment of gastric emptying
-30 min to 240 min (ingestion of meal at 0 min) on study days 1 and 7
Bodyweight
Tidsramme: Fasting state on study days 1 and 7
Fasting state on study days 1 and 7
Indirect calorimetry
Tidsramme: -30 min to 240 min (ingestion of meal at 0 min) on study days 1 and 7
Basal metabolic rate
-30 min to 240 min (ingestion of meal at 0 min) on study days 1 and 7
Ultrasound measurements
Tidsramme: -30 min to 240 min (ingestion of meal at 0 min) on study days 1 and 7
Gall bladder volume
-30 min to 240 min (ingestion of meal at 0 min) on study days 1 and 7
Visual analog scale score
Tidsramme: -30 min to 240 min (ingestion of meal at 0 min) on study days 1 and 7
Appetite
-30 min to 240 min (ingestion of meal at 0 min) on study days 1 and 7

Samarbejdspartnere og efterforskere

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

Sponsor

University Hospital, Gentofte, Copenhagen

Samarbejdspartnere

Sanofi

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. februar 2014

Primær færdiggørelse (Faktiske)

1. oktober 2015

Studieafslutning (Faktiske)

1. oktober 2015

Datoer for studieregistrering

Først indsendt

6. februar 2014

Først indsendt, der opfyldte QC-kriterier

10. februar 2014

Først opslået (Skøn)

12. februar 2014

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Skøn)

23. november 2015

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

20. november 2015

Sidst verificeret

1. november 2015

Mere information

Begreber relateret til denne undersøgelse

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • H-2-2013-148

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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