Study Stopped
GLP-2 Drug product stability concerns
Safety and Dosing Study of Glucagon-like Peptide 2 (GLP-2) in Infants and Children With Intestinal Failure
GLP-2-01
Phase 1-2 Trial of Glucagon-like Peptide 2 (GLP-2) in Infants and Children With Intestinal Failure
2 other identifiers
interventional
13
1 country
4
Brief Summary
This protocol outlines a randomized,open label trial examining the safety, pharmacology and efficacy of Glucagon like peptide 2 (GLP-2) in infants and children with intestinal failure. The investigators hypothesize that GLP-2 given subcutaneously in these patients will be well tolerated, and have similar metabolism to what has been shown in adults. The investigators also expect to show an improvement in the tolerance of enteral nutrition, and a decreased requirement for intravenous feeding.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Jan 2012
Typical duration for phase_1
4 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
January 1, 2012
CompletedFirst Submitted
Initial submission to the registry
April 5, 2012
CompletedFirst Posted
Study publicly available on registry
April 9, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
August 1, 2015
CompletedDecember 23, 2014
December 1, 2014
2.6 years
April 5, 2012
December 19, 2014
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Frequency of Adverse events
During active drug administration, patients will be monitored daily for serious adverse events. Patients will also be monitored (daily, if inpatients, bi weekly if outpatients) for clinically significant changes in safety data, vital signs, physical examination,and injection site reactions. Laboratory values of liver function and renal function will be monitored weekly for inpatients and bi weekly for outpatients. Following discontinuation of the treatment, patients will be monitored at 1 ,6 and 12 months post completion of the therapy.
One year
Pharmacokinetics (Peak serum level. Area under the curve
On days 3 and 42 of the trial, GLP-2 levels will be drawn at time 0 (before injection), 45,90 and 180 minutes post injection. Results will be analyzed for peak levels, and AUC.
Done on Day 3 and 42
Secondary Outcomes (6)
Changes in the Enteral Caloric intake
one year
Nutritional Parameters
one year
Mucosal Morphology
6 weeks
Intrinsic GLP-2 Production
One year
Septic Episodes
6 weeks
- +1 more secondary outcomes
Study Arms (2)
Intestinal Failure in children (>1 year)
EXPERIMENTALChildren requiring parenteral nutrition for \>30% of calories more than 1 year (365) days post surgery will be eligible for treatment with Glucagon-like peptide 2 (20 ug/kg/day) for 6 weeks
GLP-2 in Infants (<1 year of age)
EXPERIMENTALInfants under one year of age with congenital anomalies, or intestinal resection, leaving them with anatomic short bowel syndrome (total remaining small intestine less than 40 % of predicted for gestational age) or with intestinal resection or repaired gastroschisis who have demonstrated dependence on parenteral nutrition at 45 days post operation with the requirement for \>50% of calories by PN (independent of the length of remnant small intestine) will be eligible for treatment with Glucagon-like peptide 2, at a dose of 5, 10 or 20 ug/kg/day.
Interventions
Patients will be treated with 20 ug/kg/day GLP-2, in two doses, given subcutaneously for 3 days (Phase 1). If the treatment is well tolerated, GLP-2 will be continued for a total of 42 days.
Patients will treated with 5, 10 or 20 ug/kg/day of GLP-2, given twice daily by subcutaneous injection. The initial cohort of patients will be treated at 5 ug/kg (n=6), and if this dose is seen to be safe, and levels appropriate, the next group of 6 will be treated at 10 ug/kg/day. If this dose is seen to be safe, and levels appropriate, the final group of 6 will be treated at 20 ug/kg/day. Patients will be given GLP-2 at the assigned dose, subcutaneously for 3 days (Phase 1). If the treatment is well tolerated, GLP-2 will be continued, at the same dose, for a total of 42 days.
Eligibility Criteria
You may qualify if:
- Infants (\< 1 year corrected gestational age) Infants with congenital anomalies, or intestinal resection, leaving them with anatomic short bowel syndrome (total remaining small intestine less than 40 % of predicted for gestational age) will be eligible for treatment in the immediate post-operative period.
- Infants with intestinal resection or repaired gastroschisis who have demonstrated dependence on parenteral nutrition at 45 days post operation with the requirement for \>50% of calories by PN (independent of the length of remnant small intestine).
- Children (\> 1 year corrected gestational age) Children with a requirement for \>30% of calories by PN more than 1 year (365) days post surgery will be eligible.
You may not qualify if:
- Significant extra-intestinal disease (e.g., grade IV intraventricular hemorrhage, severe hypoxic encephalopathy);
- Significant cardiovascular, hemodynamic or respiratory instability, as noted by 1) the requirement for dopamine \> 4 mcg/kg/min, 2) high frequency ventilatory support, 3) extracorporeal membrane oxygenation.
- Hepatic disease defined as direct bilirubin \> 100 umol/L (5.2 mg/dL)
- Renal disease defined as BUN \> 80 or creatinine \> 90 μmol/L (1.5 mg/dL)
- Inborn errors of metabolism necessitating protein restriction or other special diet;
- Ongoing sepsis syndrome, as noted by refractory hypotension, thrombocytopenia, acidosis, and/or bacteremia.
- Primary motility defect such as intestinal pseudo-obstruction.
- Females who are post-pubertal must agree to comply with measures to prevent pregnancy during the study phase.
- Coagulopathy which precludes the use of subcutaneous injections.
- Allergy to GLP-2 or any of the constituent of the GLP-2 IC-115 preparation.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Alberta Children's Hospitallead
- Stollery Children's Hospitalcollaborator
- The Hospital for Sick Childrencollaborator
- British Columbia Children's Hospitalcollaborator
Study Sites (4)
Alberta Children's Hospital
Calgary, Alberta, T3B 6A8, Canada
Stollery Children's Hospital
Edmonton, Alberta, T6G 2C8, Canada
British Columbia Children's Hospital
Vancouver, British Columbia, V6H 3V4, Canada
Hospital for Sick Children
Toronto, Ontario, M5G 1X8, Canada
Related Publications (2)
Sigalet DL, de Heuvel E, Wallace L, Bulloch E, Turner J, Wales PW, Nation P, Wizzard PR, Hartmann B, Assad M, Holst JJ. Effects of chronic glucagon-like peptide-2 therapy during weaning in neonatal pigs. Regul Pept. 2014 Jan 10;188:70-80. doi: 10.1016/j.regpep.2013.12.006. Epub 2013 Dec 22.
PMID: 24368164BACKGROUNDSigalet DL, Lam V, Karnik V, Brindle M, Boctor D, Casey LW, Dicken B, Butterworth S, Stoffman S,de Heuval E, Wright-wilson G, Wallace L. Safety and Dosing Study of Glucagon-like Peptide 2 (GLP-2) in Children With Intestinal Failure DDW Abstract presented at DDW 2014, Chicago IL
RESULT
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
David Sigalet, MD PhD
Alberta Children's Hospital
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Adjunct Professor, Division of Pediatric Surgery
Study Record Dates
First Submitted
April 5, 2012
First Posted
April 9, 2012
Study Start
January 1, 2012
Primary Completion
August 1, 2014
Study Completion
August 1, 2015
Last Updated
December 23, 2014
Record last verified: 2014-12