Efficacy and Safety of Liraglutide in Subjects With Type 1 Diabetes Undergoing Islet Cell Transplantation

• Sponsor: Novo Nordisk A/S (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01206101
• Collaborator: (none)
• Enrollment: 3
• Locations: 16
• Arms: 2
• Actual Duration (Months): 14.4
• Patients Per Site: 0.2
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Diabetes; Diabetes Mellitus, Type 1	Drug: liraglutide; Drug: placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 3 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A 52 Week Randomized, Double-Blind, Placebo Controlled, Parallel Group, Multi-Center, Multinational Trial In Islet Cell Transplant Subjects With Type 1 Diabetes Mellitus To Determine If The Early Use Of Liraglutide As An Adjunct To Standard Care Increases The Proportion Of Subjects Achieving Insulin Independence After First Transplantation
• Actual Study Start Date: Mar 21, 2012
• Actual Primary Completion Date: Jun 3, 2013
• Actual Study Completion Date: Jun 3, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Liraglutide	Drug: liraglutide; 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.; Drug: placebo; 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.
Placebo Comparator: Liraglutide placebo	Drug: placebo; 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.

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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).

2. 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

3. 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

4. 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

5. 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)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novo Nordisk Investigational Site	Duarte	California	United States	91010
2	Novo Nordisk Investigational Site	Chicago	Illinois	United States	60612
3	Novo Nordisk Investigational Site	Boston	Massachusetts	United States	02114
4	Novo Nordisk Investigational Site	Madison	Wisconsin	United States	53792-0001
5	Novo Nordisk Investigational Site	Edmonton	Alberta	Canada	T6G 2C8
6	Novo Nordisk Investigational Site	Vancouver	British Columbia	Canada	V5Z 1M9
7	Novo Nordisk Investigational Site	Besancon		France	25030
8	Novo Nordisk Investigational Site	Grenoble		France	38043
9	Novo Nordisk Investigational Site	Lille		France	59037
10	Novo Nordisk Investigational Site	MONTPELLIER cedex 5		France	34295
11	Novo Nordisk Investigational Site	Strasbourg		France	67091
12	Novo Nordisk Investigational Site	Dresden		Germany	01307
13	Novo Nordisk Investigational Site	Genève 14		Switzerland	1211
14	Novo Nordisk Investigational Site	Zürich		Switzerland	8091
15	Novo Nordisk Investigational Site	Headington		United Kingdom	OX3 7LE
16	Novo Nordisk Investigational Site	London		United Kingdom	SE5 9RS

Sponsors and Collaborators

• Novo Nordisk A/S

Investigators

• Study Director: Global Clinical Registry (GCR, 1452), Novo Nordisk A/S

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Clinical Trials at Novo Nordisk

Publications

None provided.

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT01206101
• Other Study ID Numbers: NN2211-3619; 2009-013090-18; U1111-1114-8952
• First Posted: Sep 21, 2010
• Last Update Posted: Mar 30, 2017
• Last Verified: Feb 1, 2017

• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1; Liraglutide

Study Results

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 Detail	All the subjects were on pre-trial insulin at screening.

Arm/Group Title	Liraglutide	Liraglutide Placebo
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	2	1
COMPLETED	0	0
NOT COMPLETED	2	1

Baseline Characteristics

Arm/Group Title	Liraglutide	Liraglutide Placebo	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	2	1	3
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	2 100%	1 100%	3 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	1 50%	1 100%	2 66.7%
Male	1 50%	0 0%	1 33.3%

Outcome Measures

1. Primary Outcome

Title	Proportion Of Insulin-independent Subjects After Receiving Only One (Single-Donor) Islet Cell Transplant
Description	Proportion Of Insulin-independent Subjects After Receiving Only One (Single-Donor) Islet Cell Transplant.
Time Frame	At week 52 after initial transplantation

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Liraglutide	Liraglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	0	0

2. Secondary Outcome

Title	Number of Hypoglycaemic Episodes
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Liraglutide	Liraglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	0	0

3. Secondary Outcome

Title	Proportion of Subjects With HbA1c Below Or Equal to 6.5% At Week 52 That Are Free From Severe Hypoglycaemic Events
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Liraglutide	Liraglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	0	0

4. Secondary Outcome

Title	Proportion of Insulin-Independent Subjects
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Liraglutide	Liraglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	0	0

5. Secondary Outcome

Title	Change in Islet Cell Yield During Culture
Description	Change in islet cell yield from pre-culture to post-culture
Time Frame	From 0 hours pre-culture to 24 hours to 72 hours

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Liraglutide	Liraglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	0	0

6. Secondary Outcome

Title	Glucose Level Variability And Hypoglycaemia Duration Derived From The Continuous Glucose Monitoring System (CGMS)
Description	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Liraglutide	Liraglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	0	0

Adverse Events

Time Frame	Adverse events were collected from week 0 to week 52.
Adverse Event Reporting Description	Safety analysis set includes all subjects who received at least one dose of the trial product or its comparator.
Arm/Group Title	Liraglutide		Liraglutide Placebo
Arm/Group Description	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.		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.
All Cause Mortality
	Liraglutide		Liraglutide Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Liraglutide		Liraglutide Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/1 (0%)
Other (Not Including Serious) Adverse Events
	Liraglutide		Liraglutide Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/2 (100%)		1/1 (100%)
Gastrointestinal disorders
Gastric ulcer	0/2 (0%)	0	1/1 (100%)	1
Nausea	2/2 (100%)	2	1/1 (100%)	1
Vomiting	1/2 (50%)	1	0/1 (0%)	0
General disorders
Fatigue	1/2 (50%)	1	0/1 (0%)	0
Pyrexia	0/2 (0%)	0	1/1 (100%)	1
Infections and infestations
Pharyngitis	0/2 (0%)	0	1/1 (100%)	1
Investigations
Computerised tomogram abnormal	0/2 (0%)	0	1/1 (100%)	1
Metabolism and nutrition disorders
Decreased appetite	1/2 (50%)	1	0/1 (0%)	0
Hypoglycaemia	1/2 (50%)	3	0/1 (0%)	0
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain	0/2 (0%)	0	1/1 (100%)	1
Nervous system disorders
Headache	1/2 (50%)	1	1/1 (100%)	1
Psychiatric disorders
Depression	0/2 (0%)	0	1/1 (100%)	1
Respiratory, thoracic and mediastinal disorders
Nasal congestion	0/2 (0%)	0	1/1 (100%)	1

Limitations/Caveats

Due to the premature termination of the trial prior to islet cell transplantation in any randomised subject, no results are available.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Novo Nordisk maintains the right to be informed of any Investigator plans for publication and to review any scientific paper, presentation, communication or other information concerning the investigation described in this protocol. Any such communication must be submitted in writing to the Novo Nordisk trial manager prior to submission for comments. Comments will be given within four weeks from receipt of the planned communication.