Diabetes, Diabetes Mellitus, Type 1
Conditions
Brief summary
This trial is conducted in Europe and North America. The aim of this trial is to investigate if liraglutide treatment can increase the proportion of insulin-independent subjects one year after islet cell transplantation who required only one (single-donor) islet cell transplant.
Interventions
DRUGliraglutide
Dose escalation of liraglutide up to 1.2 to 1.8 mg before islet cell transplant until the planned number of transplanted subjects is complete or subject is transplanted. After islet cell transplant, subjects continue to receive the reached liraglutide dose for 52 weeks. Injected subcutaneously(under the skin) once daily.
DRUGplacebo
Dose escalation escalation of liraglutide up to 1.2 to 1.8 mg before islet cell transplant until the planned number of transplanted subjects is complete or subject is transplanted. After islet cell transplant, subjects continue to receive the reached liraglutide placebo dose for 52 weeks. Injected subcutaneously (under the skin) once daily.
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Type 1 diabetes mellitus for at least 5 years * Candidate for islet cell transplantation based upon local accepted practice and guidelines * Reduced awareness of hypoglycaemia
Exclusion criteria
* Treatment with any anti-diabetic medication other than insulin including insulin pump within 4 weeks of trial start * Any previous organ transplantation * A history of acute idiopathic or chronic pancreatitis * Family or personal history of multiple endocrine neoplasia type 2 (MEN2) or familial medullary thyroid carcinoma (FMTC)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion Of Insulin-independent Subjects After Receiving Only One (Single-Donor) Islet Cell Transplant | At week 52 after initial transplantation | Proportion Of Insulin-independent Subjects After Receiving Only One (Single-Donor) Islet Cell Transplant. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Hypoglycaemic Episodes | During week 0 to week 52 | A hypoglycaemic episode was defined as treatment emergent if the onset of the episode was on or after the first day of exposure to randomised treatment and until the last day on randomised treatment. Confirmed hypoglycaemic episodes were categorised either as minor (PG\<3.1 mmol/L \[56 mg/dL\]) or severe (subject unable to treat himself/herself). |
| Proportion of Subjects With HbA1c Below Or Equal to 6.5% At Week 52 That Are Free From Severe Hypoglycaemic Events | From week 0 to week 52 after initial transplantation | Proportion of subjects with HbA1c below or equal to 6.5% at week 52 that were free from severe hypoglycaemic events |
| Proportion of Insulin-Independent Subjects | At 52 weeks after initial transplantation | Proportion of insulin-independent subjects among all randomised subjects who had one or more transplantations after randomisation |
| Change in Islet Cell Yield During Culture | From 0 hours pre-culture to 24 hours to 72 hours | Change in islet cell yield from pre-culture to post-culture |
| Glucose Level Variability And Hypoglycaemia Duration Derived From The Continuous Glucose Monitoring System (CGMS) | At 12 weeks pre-transplant, at 24 weeks post-transplant, 52 weeks post-transplant and 56 weeks (4 weeks after withdrawal of liraglutide or liraglutide placebo) | Change from baseline in glucose level variability and hypoglycaemia at baseline, weekly during liraglutide dose escalation, at 12 weeks pre-transplant, at 24 weeks post-transplant, 52 weeks post-transplant and 56 weeks (4 weeks after withdrawal of liraglutide or liraglutide placebo) |
Countries
Canada, France, Germany, Switzerland, United Kingdom, United States
Participant flow
Recruitment details
The trial was conducted at 3 sites in 3 countries: Canada: 1 site; Switzerland: 1 site; US: 1 site.
Pre-assignment details
All the subjects were on pre-trial insulin at screening.
Participants by arm
| Arm | Count |
|---|---|
| Liraglutide Liraglutide was injected subcutaneously once-daily. The dose of liraglutide was escalated up to 1.8 mg (or 1.2 mg if 1.8 mg not tolerated) prior to islet cell transplant and continued until one year after the first transplant in each subject. | 2 |
| Liraglutide Placebo Liraglutide placebo was injected subcutaneously once-daily. The dose of liraglutide placebo was escalated up to 1.8 mg (or 1.2 mg if 1.8 mg not tolerated) prior to islet cell transplant and continued until one year after the first transplant in each subject. | 1 |
| Total | 3 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Unclassified | 1 | 0 |
Baseline characteristics
| Characteristic | Liraglutide | Liraglutide Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 1 Participants | 0 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 2 | 1 / 1 |
| serious Total, serious adverse events | 0 / 2 | 0 / 1 |
Outcome results
Primary
Proportion Of Insulin-independent Subjects After Receiving Only One (Single-Donor) Islet Cell Transplant
Proportion Of Insulin-independent Subjects After Receiving Only One (Single-Donor) Islet Cell Transplant.
Time frame: At week 52 after initial transplantation
Population: Full analysis set (FAS) - all randomised subjects who underwent one or more transplantations after randomisation. Due to the premature termination of the trial prior to islet cell transplantation in any randomised subject, no formal statistical analyses were performed.
Secondary
Change in Islet Cell Yield During Culture
Change in islet cell yield from pre-culture to post-culture
Time frame: From 0 hours pre-culture to 24 hours to 72 hours
Population: Full analysis set (FAS) - all randomised subjects who underwent one or more transplantations after randomisation. Due to the premature termination of the trial prior to islet cell transplantation in any randomised subject, no formal statistical analyses were performed.
Secondary
Glucose Level Variability And Hypoglycaemia Duration Derived From The Continuous Glucose Monitoring System (CGMS)
Change from baseline in glucose level variability and hypoglycaemia at baseline, weekly during liraglutide dose escalation, at 12 weeks pre-transplant, at 24 weeks post-transplant, 52 weeks post-transplant and 56 weeks (4 weeks after withdrawal of liraglutide or liraglutide placebo)
Time frame: At 12 weeks pre-transplant, at 24 weeks post-transplant, 52 weeks post-transplant and 56 weeks (4 weeks after withdrawal of liraglutide or liraglutide placebo)
Population: Full analysis set (FAS) - all randomised subjects who underwent one or more transplantations after randomisation. Due to the premature termination of the trial prior to islet cell transplantation in any randomised subject, no formal statistical analyses were performed.
Secondary
Number of Hypoglycaemic Episodes
A hypoglycaemic episode was defined as treatment emergent if the onset of the episode was on or after the first day of exposure to randomised treatment and until the last day on randomised treatment. Confirmed hypoglycaemic episodes were categorised either as minor (PG\<3.1 mmol/L \[56 mg/dL\]) or severe (subject unable to treat himself/herself).
Time frame: During week 0 to week 52
Population: Full analysis set (FAS) - all randomised subjects who underwent one or more transplantations after randomisation. Due to the premature termination of the trial prior to islet cell transplantation in any randomised subject, no formal statistical analyses were performed.
Secondary
Proportion of Insulin-Independent Subjects
Proportion of insulin-independent subjects among all randomised subjects who had one or more transplantations after randomisation
Time frame: At 52 weeks after initial transplantation
Population: Full analysis set (FAS) - all randomised subjects who underwent one or more transplantations after randomisation. Due to the premature termination of the trial prior to islet cell transplantation in any randomised subject, no formal statistical analyses were performed.
Secondary
Proportion of Subjects With HbA1c Below Or Equal to 6.5% At Week 52 That Are Free From Severe Hypoglycaemic Events
Proportion of subjects with HbA1c below or equal to 6.5% at week 52 that were free from severe hypoglycaemic events
Time frame: From week 0 to week 52 after initial transplantation
Population: Full analysis set (FAS) - all randomised subjects who underwent one or more transplantations after randomisation. Due to the premature termination of the trial prior to islet cell transplantation in any randomised subject, no formal statistical analyses were performed.