Denne siden ble automatisk oversatt og nøyaktigheten av oversettelsen er ikke garantert. Vennligst referer til engelsk versjon for en kildetekst.

The Late Effects of Ethanol Intake on the Glucose Response to Subcutaneous Glucagon in Type 1 Diabetes (ALCO1)

20. juli 2017 oppdatert av: Ajenthen Ranjan, Hvidovre University Hospital

Objective: Because many people with type 1 diabetes drink ethanol and because glucagon is used to treat mild hypoglycaemia, it is essential to determine whether ethanol will impair the effectiveness of glucagon to increase glucose, which may impair the effectiveness of the dual hormone treatment in preventing hypoglycaemia.

The purpose of this study is to determine, whether ethanol influences the glucose response to subcutaneous glucagon during mild hypoglycaemia.

The investigators hypothesize that prior evening ethanol consumption does not reduce the effect of a glucagon bolus to raise plasma glucose compared with no prior ethanol consumption.

The study aims:

  1. To determine the late effects of ethanol on the efficacy of subcutaneous glucagon to restore plasma glucose after an episode of mild hypoglycemia.
  2. To determine the late effects of ethanol on the counter-regulatory hormones and hypoglycaemia awareness during mild hypoglycaemia

A double-blinded placebo-controlled study will be conducted. Participants will serve as their own controls. Eligible participants will after an informed consent complete two study visits, one with and one without ethanol consumption, in a random order. On each study visit, participants are induced a insulin induced hypoglycemia, seven-eight hours after a meal with or without ethanol. Once plasma glucose is below 3.9 mmol/l, a subcutaneous injection of 100 mcg glucagon is administered. Two hours later a second bolus is administered.

Studieoversikt

Studietype

Intervensjonell

Registrering (Faktiske)

12

Fase

  • Fase 4

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

      • Hvidovre, Danmark, 2650
        • Hvidovre University Hospital

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 70 år (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

Inclusion Criteria:

  • Age 18 - 70 years
  • T1D ≥ 3 year
  • BMI 20-28 kg/m2
  • CSII ≥ 1 year
  • Caucasian origin
  • Hypoglycaemia awareness (assessed by Gold, Clarke and Pedersen-Bjergaard methods)
  • Use of carbohydrate counting and the insulin pump bolus calculator for all meals
  • Ethanol exposure once within 1 year consisting of at least 4 drinks (1 drink contains 12 gram ethanol) within four hours

Exclusion Criteria:

  • Allergy or intolerance to lactose or Glucagen®(Novo Nordisk, Bagsværd, DK)
  • Allergy for ethanol or any food ingredients that will be used in the study.
  • Impaired renal function (eGFR < 60 ml/min/1.73m2)
  • Liver disease with ALAT > 2.5 times the upper limit of the reference interval
  • Gastropareses (beat-beat variation < 10 beats per min and/or orthostatic systolic blood pressure > 20 mmHg)
  • Insomnia, sleep apnoea or any troubles with sleeping that according to the investigator's assessment makes the individual unsuitable for study participation.
  • Aldehyde dehydrogenase deficiency as determined by a screening questionnaire
  • Unable to refrain from the consumption of ethanol at least 24 hours prior to study start
  • History of drinking problems or alcoholism, regardless of whether active or in remission.
  • Use of benzodiazepines or barbiturates or opiates or other central nervous system depressant drugs that could act synergistically with ethanol to lower the level of consciousness
  • History of drug abuse
  • Current participation in another diabetes-related clinical trial that, in the judgment of the principle investigator, will compromise the results of the study or the safety of the subject.
  • Use of anti-diabetic medicine (other than insulin), corticosteroids or other drugs affecting glucose metabolism during the study period or within 30 days prior to study start
  • Use of medications that are known to cause QT interval prolongation
  • Presence of pheochromocytoma
  • Other concomitant medical or psychological condition that according to the investigator's assessment makes the individual unsuitable for study participation
  • Females who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods.
  • Females who have different basal insulin pattern depending on their menstrual cycle.
  • Inability to understand the individual information and to give informed consent.

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: Randomisert
  • Intervensjonsmodell: Crossover-oppdrag
  • Masking: Dobbelt

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Aktiv komparator: Ethanol
Drinking a cocktail of ethanol (0.8 g ethanol per kg body weight), diet lemonade and water of 1:1:1 (volume distribution).
Andre navn:
  • Cocktail
Placebo komparator: Non-ethanol
Drinking a cocktail of diet lemonade and water of 1:2 (volume distribution).
Andre navn:
  • Mocktail

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Increase in plasma glucose
Tidsramme: 0-120 min after the first glucagon injection
The primary endpoint is difference in increase in plasma glucose value after the first injection of 100 µg s.c. glucagon on study nights with ethanol vs. study nights without ethanol consumption.
0-120 min after the first glucagon injection

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Peak plasma glucose
Tidsramme: 0-240 min after the first glucagon injection
Maximal plasma glucose after the first and second glucagon injection
0-240 min after the first glucagon injection
Increase in plasma glucose
Tidsramme: 0-120 min after the second glucagon injection
Increase in plasma glucose caused by the second glucagon injection.
0-120 min after the second glucagon injection
Total AUC(0-120)
Tidsramme: 0-240 min after the first glucagon injection
Total area under the glucose curve from 0-120 minutes after each glucagon injection
0-240 min after the first glucagon injection
PI-AUC(0-120)
Tidsramme: 0-240 min after the first glucagon injection
positive incremental area under the glucose curve from 0-120 minutes after each glucagon injection
0-240 min after the first glucagon injection
Tmax
Tidsramme: 0-240 min after the first glucagon injection
Time-to-peak glucose value after each glucagon injection glucagon injection
0-240 min after the first glucagon injection
Time above 4.0mM
Tidsramme: 0-240 min after the first glucagon injection
Duration of glucose above 4.0 mmol/l after first and second glucagon injection
0-240 min after the first glucagon injection
Time above baseline
Tidsramme: 0-240 min after the first glucagon injection
Duration of glucose above baseline after first and second glucagon injection
0-240 min after the first glucagon injection
Rescue rates
Tidsramme: 0-240 min after the first glucagon injection
Numbers of first and second glucagon injections that raises PG > 4.9 mmol/l
0-240 min after the first glucagon injection
Hyperglycemia rates
Tidsramme: 0-240 min after the first glucagon injection
Number of first and second glucagon injections that raises PG > 7.1 mmol/l
0-240 min after the first glucagon injection
Changes in plasma ketone bodies, measured as area under the curve
Tidsramme: 0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Changes in plasma ketone bodies, measured as incremental peak
Tidsramme: 0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Changes in plasma glucagon, measured as area under the curve
Tidsramme: 0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Changes in plasma glucagon, measured as incremental peak
Tidsramme: 0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Changes in insulin, measured as area under the curve
Tidsramme: 0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Changes in insulin, measured as incremental peak
Tidsramme: 0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Changes in growth hormones, measured as area under the curve
Tidsramme: 0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Changes in growth hormones, measured as incremental peak
Tidsramme: 0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Changes in serum corticole, measured as area under the curve
Tidsramme: 0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Changes in serum corticole, measured as incremental peak
Tidsramme: 0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Changes in plasma ethanol, measured as area under the curve
Tidsramme: 0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Changes in plasma ethanol, measured as incremental peak
Tidsramme: 0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Changes in free fatty acids, measured as area under the curve
Tidsramme: 0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Changes in free fatty acids, measured as incremental peak
Tidsramme: 0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Changes in triglycerides, measured as area under the curve
Tidsramme: 0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Changes in triglycerides, measured as incremental peak
Tidsramme: 0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Average in blood pressure
Tidsramme: 0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Average heart rate
Tidsramme: 0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Intensity of hypoglycemia
Tidsramme: 0-240 min after the first glucagon injection
Average changes in Edinburgh Hypoglycaemia Scale over time during insulin and glucagon phase
0-240 min after the first glucagon injection
Cognitive impairment
Tidsramme: 0-240 min after the first glucagon injection
Average scores in cognitive test 30 min before each glucagon injection.
0-240 min after the first glucagon injection
Side effects
Tidsramme: 0-240 min after the first glucagon injection
Average visual analogue scale score from 0-180 min for nausea and headache after glucagon injection
0-240 min after the first glucagon injection
Incidence of vomiting
Tidsramme: 0-240 min after the first glucagon injection
Incidence of vomiting after 0-4 hours after each glucagon injection.
0-240 min after the first glucagon injection
Meal induced glucose excursion
Tidsramme: 0-3 hours after meal
Total and incremental area under the glucose curve from 0-120 and 0-240 min after eating the mixed meal
0-3 hours after meal
Meal induced hormonal changes
Tidsramme: 0-3 hours after meal
Total and incremental area under the glucose curve from 0-120 and 0-240 min after eating the mixed meal
0-3 hours after meal
Nocturnal changes in plasma glucose
Tidsramme: 0-6 hours after start of sleep
Area under the curve during sleep
0-6 hours after start of sleep
Nocturnal changes in corticol
Tidsramme: 0-6 hours after start of sleep
Area under the curve during sleep
0-6 hours after start of sleep
Nocturnal changes in growth hormone
Tidsramme: 0-6 hours after start of sleep
Area under the curve during sleep
0-6 hours after start of sleep
Nocturnal changes in ketones
Tidsramme: 0-6 hours after start of sleep
Area under the curve during sleep
0-6 hours after start of sleep
Nocturnal changes in ethanol
Tidsramme: 0-6 hours after start of sleep
Area under the curve during sleep
0-6 hours after start of sleep
Nocturnal changes in glucagon
Tidsramme: 0-6 hours after start of sleep
Area under the curve during sleep
0-6 hours after start of sleep
Difference between the first second glucagon injection and between both study visits in peak change plasma glucose
Tidsramme: 0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Difference between glucagon injections on both study visits in positive incremental area under the glucose curve from 0-120 minutes
Tidsramme: 0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Difference between glucagon injections on both study visits in total area under the glucose curve from 0-120 minutes
Tidsramme: 0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Difference between glucagon injections on both study visits in time-to-peak glucose value
Tidsramme: 0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Difference between glucagon injections on both study visits in duration of glucose above 4.0 mmol/l after first and second glucagon injection
Tidsramme: 0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Difference between glucagon injections on both study visits in duration of glucose above baseline after first and second glucagon injection
Tidsramme: 0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Difference in glucose sensor data on study night with alcohol vs. study night without alcohol - Mean absolute relative difference (MARD) values of glucose sensors compared with YSI from 7 PM- 8 AM.
Tidsramme: 0-10 hours after meal
Intentions to treat analysis
0-10 hours after meal
Difference in glucose sensor data on study night with alcohol vs. study night without alcohol - Precision absolute relative difference (PARD) 120 min before and 120 after each glucagon injection.
Tidsramme: 0-10 hours after meal
Intentions to treat analysis
0-10 hours after meal
Difference in glucose sensor data on study night with alcohol vs. study night without alcohol - MARD values between glucose sensors 0-120 minutes after each glucagon injection.
Tidsramme: 0-10 hours after meal
Intentions to treat analysis
0-10 hours after meal
Difference in glucose sensor data within 2 days after study night with alcohol vs. study night without alcohol - Time in range (glucose sensor value =4.0-10.0mmol/l)
Tidsramme: 0-2 days after the first glucagon injection
Intentions to treat analysis
0-2 days after the first glucagon injection
Difference in glucose sensor data within 2 days after study night with alcohol vs. study night without alcohol - Time in hypoglycaemia (glucose sensor value < 4.0 mmol/l)
Tidsramme: 0-2 days after the first glucagon injection
Intentions to treat analysis
0-2 days after the first glucagon injection
Difference in glucose sensor data within 2 days after study night with alcohol vs. study night without alcohol - Time in hyperglycaemia (glucose sensor value >10.0mmol/l)
Tidsramme: 0-2 days after the first glucagon injection
Intentions to treat analysis
0-2 days after the first glucagon injection
Difference in glucose sensor data within 2 days after study night with alcohol vs. study night without alcohol - Number of hypoglycaemia episodes (glucose sensor value < 4.0 mmol/l)
Tidsramme: 0-2 days after the first glucagon injection
Intentions to treat analysis
0-2 days after the first glucagon injection
Difference in glucose sensor data between the study period with and without alcohol - Clarke- Error Grid analysis for both sensors compared with YSI during study visit
Tidsramme: -2 to 4 days after study visits
Intentions to treat analysis
-2 to 4 days after study visits
Difference in glucose sensor data between the study period with and without alcohol - PARD values from day 1-7
Tidsramme: -2 to 4 days after study visits
Intentions to treat analysis
-2 to 4 days after study visits
Difference in glucose sensor data between the study period with and without alcohol - PARD values <4.0 mmol/L from day 1-7
Tidsramme: -2 to 4 days after study visits
Intentions to treat analysis
-2 to 4 days after study visits
Difference in glucose sensor data between the study period with and without alcohol - PARD values 4.0-10.0 mmol/L from day 1-7
Tidsramme: -2 to 4 days after study visits
Intentions to treat analysis
-2 to 4 days after study visits
Difference in glucose sensor data between the study period with and without alcohol PARD values >10.0 mmol/L from day 1-7
Tidsramme: -2 to 4 days after study visits
Intentions to treat analysis
-2 to 4 days after study visits
Difference in glucose sensor data between the study period with and without alcohol - Number of hypoglycaemia episodes (glucose sensor value < 4.0 mmol/l)
Tidsramme: -2 to 4 days after study visits
Intentions to treat analysis
-2 to 4 days after study visits

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Etterforskere

  • Hovedetterforsker: Ajenthen Ranjan, MD, Hvidovre University Hospital

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. august 2016

Primær fullføring (Faktiske)

26. januar 2017

Studiet fullført (Faktiske)

26. januar 2017

Datoer for studieregistrering

Først innsendt

11. august 2016

Først innsendt som oppfylte QC-kriteriene

23. august 2016

Først lagt ut (Anslag)

26. august 2016

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

24. juli 2017

Siste oppdatering sendt inn som oppfylte QC-kriteriene

20. juli 2017

Sist bekreftet

1. juli 2017

Mer informasjon

Begreper knyttet til denne studien

Plan for individuelle deltakerdata (IPD)

Planlegger du å dele individuelle deltakerdata (IPD)?

UBESLUTTE

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

Kliniske studier på Placebo

3
Abonnere