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

20 de julho de 2017 atualizado por: 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.

Visão geral do estudo

Tipo de estudo

Intervencional

Inscrição (Real)

12

Estágio

  • Fase 4

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Locais de estudo

      • Hvidovre, Dinamarca, 2650
        • Hvidovre University Hospital

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

18 anos a 70 anos (Adulto, Adulto mais velho)

Aceita Voluntários Saudáveis

Não

Gêneros Elegíveis para o Estudo

Tudo

Descrição

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.

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

  • Finalidade Principal: Tratamento
  • Alocação: Randomizado
  • Modelo Intervencional: Atribuição cruzada
  • Mascaramento: Dobro

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Comparador Ativo: Ethanol
Drinking a cocktail of ethanol (0.8 g ethanol per kg body weight), diet lemonade and water of 1:1:1 (volume distribution).
Outros nomes:
  • Coquetel
Comparador de Placebo: Non-ethanol
Drinking a cocktail of diet lemonade and water of 1:2 (volume distribution).
Outros nomes:
  • Mocktail

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Increase in plasma glucose
Prazo: 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

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Peak plasma glucose
Prazo: 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
Prazo: 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)
Prazo: 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)
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Changes in plasma glucagon, measured as incremental peak
Prazo: 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
Prazo: 0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Changes in insulin, measured as incremental peak
Prazo: 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
Prazo: 0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Changes in growth hormones, measured as incremental peak
Prazo: 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
Prazo: 0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Changes in serum corticole, measured as incremental peak
Prazo: 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
Prazo: 0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Changes in plasma ethanol, measured as incremental peak
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Changes in triglycerides, measured as incremental peak
Prazo: 0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Average in blood pressure
Prazo: 0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Average heart rate
Prazo: 0-240 min after the first glucagon injection
0-240 min after the first glucagon injection
Intensity of hypoglycemia
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 0-6 hours after start of sleep
Area under the curve during sleep
0-6 hours after start of sleep
Nocturnal changes in corticol
Prazo: 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
Prazo: 0-6 hours after start of sleep
Area under the curve during sleep
0-6 hours after start of sleep
Nocturnal changes in ketones
Prazo: 0-6 hours after start of sleep
Area under the curve during sleep
0-6 hours after start of sleep
Nocturnal changes in ethanol
Prazo: 0-6 hours after start of sleep
Area under the curve during sleep
0-6 hours after start of sleep
Nocturnal changes in glucagon
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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.
Prazo: 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.
Prazo: 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.
Prazo: 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)
Prazo: 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)
Prazo: 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)
Prazo: 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)
Prazo: 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
Prazo: -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
Prazo: -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
Prazo: -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
Prazo: -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
Prazo: -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)
Prazo: -2 to 4 days after study visits
Intentions to treat analysis
-2 to 4 days after study visits

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Investigadores

  • Investigador principal: Ajenthen Ranjan, MD, Hvidovre University Hospital

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo

1 de agosto de 2016

Conclusão Primária (Real)

26 de janeiro de 2017

Conclusão do estudo (Real)

26 de janeiro de 2017

Datas de inscrição no estudo

Enviado pela primeira vez

11 de agosto de 2016

Enviado pela primeira vez que atendeu aos critérios de CQ

23 de agosto de 2016

Primeira postagem (Estimativa)

26 de agosto de 2016

Atualizações de registro de estudo

Última Atualização Postada (Real)

24 de julho de 2017

Última atualização enviada que atendeu aos critérios de controle de qualidade

20 de julho de 2017

Última verificação

1 de julho de 2017

Mais Informações

Termos relacionados a este estudo

Plano para dados de participantes individuais (IPD)

Planeja compartilhar dados de participantes individuais (IPD)?

INDECISO

Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .

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