E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary objective:To investigate the effect of liraglutide 1.8 mg once daily compared to placebo for 24 weeks on change in HbA1c in patients with type 1 diabetes as an add-on therapy to insulin.
Secondary objectives:To investigate the effect of liraglutide as an add-on therapy to insulin compared to placebo on change in:Weight, insulin dose,hypoglycaemic events, CGM, BMI, body composition, quality of life, treatment satisfaction,food preferences, meal test, CIMT, PWV and 24 hour blood pressure. |
Primært formål:At undersøge effekten af liraglutid 1,8 mg én gang dagligt som et supplement til insulinbehandling sammenlignet med placebo i 24 uger på ændring i HbA1c.
Sekundært formål:At undersøge effekten af liraglutid 1,8 mg én gang dagligt som et supplement til insulinbehandling sammenlignet med placebo på ændring i: vægt, insulindoser, hypoglykæmi, CGM, BMI, kropssammensætning, livskvalitet, problemområder indenfor diabetes, mad præferencer, måltidstest, CIMT, karstivhed og døgn blodtryk. |
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E.1.1.1 | Medical condition in easily understood language |
To investigate the effect of liraglutide on change in HbA1c, weight and hypoglycaemic events in patients with type 1 diabetes. |
At undersøge effekten af liraglutid på ændring i langtidsblodsukker, vægttab og hyppigheden af lavt blodsukker hos patienter med type 1 diabetes. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067584 |
E.1.2 | Term | Type 1 diabetes mellitus |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate the effect of liraglutide 1.8 mg once daily compared to placebo for 24 weeks on change in HbA1c in patients with type 1 diabetes as an adjunctive therapy to insulin treatment.
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At undersøge effekten af liraglutid 1,8 mg én gang dagligt som et supplement til insulinbehandling sammenlignet med placebo i 24 uger på ændring i HbA1c.
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E.2.2 | Secondary objectives of the trial |
To investigate the effect of liraglutide as an adjunctive therapy to insulin treatment compared to placebo on change in: Weight, insulin dose, hypoglycaemic events, glycaemic excursions (time spent in hypo- and hyperglycaemia as measured by CGM), BMI, body composition, quality of life and treatment satisfaction, food preferences, VAS score for appetite, standardised liquid meal test for postprandial glucagon levels and glycaemic excursions, gastric emptying via serum paracetamol measurements, CIMT, PWV and 24 hour blood pressure. |
At undersøge effekten af liraglutid 1,8 mg én gang dagligt som et supplement til insulinbehandling sammenlignet med placebo på ændring i: vægt, insulindoser, hypoglykæmi, CGM, BMI, kropssammensætning, livskvalitet og problemområder indenfor diabetes, mad præferencer, VAS score for appetit, stardardiseret flydende måltidstest for postprandiale glycagonniveauer og glykæmiske parametre, ventrikeltømningshastighed via paracetamol målinger, CIMT, pulsbølgehastighed og døgn blodtryk. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Type 1 diabetes according to WHO criteria ≥ 1 year
• Age ≥ 18 years
• BMI > 25 kg/m2
• HbA1c > 8.0 % at visit 0 |
• Type 1 diabetes i ≥ 1 år
• Alder ≥ 18 år
• BMI > 25 kg/m2
• HbA1c > 8 % ved besøg 0
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E.4 | Principal exclusion criteria |
• Insulin pump treatment
• Hypoglycaemia unawareness (unability to register low blood glucose)
• Diabetic gastroparesis
• Compromised kidney function (eGFR < 60 ml/min/1,73m2), dialysis or kidney transplantation at visit 0
• Liver disease with elevated plasma alanine aminotransferase (ALT) > three times the upper limit of normal (measured at visit 0 with the possibility of one repeat analysis within a week, and the last measured value as being conclusive)
• Acute or chronic pancreatitis
• Inflammatory bowel disease
• Cancer unless in complete remission for > 5 years
• History of thyroid adenoma or carcinoma
• Alcohol/drug abuse
• Fertile women not using contraceptives
• Pregnant or nursing women
• Simultaneous participation in any other clinical intervention trial |
• Insulin pumpe
• Hypoglykæmi unawarenes (manglende føling ved lavt blodsukker)
• Diabetisk gastroparese
• Nedsat nyrefunktion med eGFR < 60 ml/min/1,73 m2, dialyse patient eller nyretransplanteret ved besøg 0
• Leversygdom med ALAT (alanin-aminotransferase) forhøjelse > 3 gange den øvre normalværdi, med mulighed for at gentage analysen indenfor 1 uge, og den sidste måling som værende afgørende
• Akut eller kronisk pankreatitis
• Inflammatorisk tarmsygdom
• Tidligere kræftsygdom, medmindre patienten har været sygdomsfri i > 5 år
• Tidligere godartede eller ondartede knuder i skjoldbryskkirtlen
• Alkohol eller stof misbrug
• Fertile kvinder, der ikke bruger præventionsmidler
• Gravide eller ammende kvinder
• Samtidig deltagelse i et andet klinisk interventionsstudie |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in HbA1c from visit 1 to the end of treatment after 24 weeks of intervention. |
Ændring i HbA1c fra besøg 1 til studieafslutning efter 24 ugers behandling. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At the end of treatment after 24 weeks of intervention. |
Til afslutningsbesøget efter 24 ugers behandling. |
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E.5.2 | Secondary end point(s) |
Changes from visit 1 to the end of treatment after 24 weeks of intervention in:
• Weight
• Insulin dose
• Hypoglycaemic events
• Glycaemic excursions (time spent in hypo- and hyperglycaemia as measured by CGM)
• BMI
• Lean body mass and fat mass composition as determined by Dual-Energy X-ray absorptiometry (DXA) scan
• Quality of life and treatment satisfaction
• Food preferences
• VAS score for appetite
• Standardised liquid mixed meal test for postprandial glucagon levels and glycaemic excursion
• Gastric emptying via serum paracetamol measurements
• Carotis intima media thickness
• Pulse wave velocity
• 24 hour blood pressure and pulse rate |
Ændring fra besøg 1 til studieafslutning efter 24 ugers behandling i:
• Vægt
• Insulindoser
• Tilfælde af hypoglykæmi
• Glykæmiske parametre (tid med hypo- og hyperglykæmi målt ved CGM)
• BMI
• Kropssammensætning målt ved DXA scanning
• Livskvalitet og problemområder indenfor diabetes
• Mad præferencer
• VAS score for appetit
• Stardardiseret flydende måltidstest for postprandiale glycagonniveauer og glykæmiske parametre
• Ventrikeltømningshastighed via paracetamol målinger
• Carotis intima media tykkelsen
• Pulsbølgehastighed
• 24-timers blodtryk og puls |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At the end of treatment after 24 weeks of intervention. |
Til afslutningsbesøget efter 24 ugers behandling. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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• Pregnancy or desire hereof
• Safety considerations as assessed by the investigator
• Withdrawal of informed consent
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• Graviditet eller ønsker herom
• Sikkerhedshensyn vurderet af investigator
• Tilbagetrækning af informeret samtykke |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |