NCT01573286

Safety and Dosing Study of Glucagon-like Peptide 2 (GLP-2) in Infants and Children With Intestinal Failure

Phase 1-2 Trial of Glucagon-like Peptide 2 (GLP-2) in Infants and Children With Intestinal Failure

• Status: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 13 (actual)
• Sponsor: Alberta Children's Hospital · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

GLP-2 (1-33) is a naturally occurring peptide which is important in controlling the function of the intestine. In previous studies our group has shown that serum levels of GLP-2 correlate with intestinal function in human neonates. Low levels of GLP-2 are predictive of intestinal malabsorption and the development of the so called "Short Bowel Syndrome". GLP-2 has been shown to be specifically trophic for the GI tract, especially for the small intestine. This proposal outlines a Phase 1 and 2 trial using subcutaneous administration, twice daily of GLP-2 in human infants and children with Intestinal Failure, typically from Short Bowel Syndrome, using varying doses, assigned in a prospective, randomized protocol, with open label monitoring. The investigational plan is to begin with the Phase 1 trial, administering GLP 2 at varying doses (infants assigned to doses of 5,10, or 20 μg/kg/day, children greater than 1 year dosed at 20 μg/kg/day, given via twice daily subcutaneous injection). Eligible subjects will be infants (less than 12 months corrected gestational age) with either major resection (remaining small intestine less than 40% of predicted length for gestational age), or demonstrated intestinal failure after intestinal resection/abdominal surgery/gastroschisis (Requirement for parenteral nutrition greater than 50% of total calories, more than 45 days after the last surgery). Infants will be allocated sequentially to a group (n = 6 per group) treated with GLP-2 at 5,10, or 20 μg/kg/day. Older children (greater than 1 year of age), requiring PN for \>30% calories\> one year post surgery will also be eligible; these patients will be dosed at 20 μg/kg/day (via twice daily subcutaneous injection) n= 7. Patients will be followed on the principle of intention to treat after initial randomization. The endpoints will be monitoring for safety, and recording of adverse events and a pharmacokinetic profile at 3 days. If the hormone is well tolerated these studies will be extended into a phase 2 study, for an additional 39 days; monitoring safety, patient tolerance of enteral nutrition, growth, citrulline levels, nutrient absorptive capacity, liver function and repeat pharmacokinetic studies.

Conditions

• Intestinal Failure
• Short Bowel Syndrome

Interventions

Type	Name	Description
DRUG	Glucagon-Like Peptide 2	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.
DRUG	Glucagon like peptide-2	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.

Timeline

• Start date: 2012-01-01
• Primary completion: 2014-08-01
• Completion: 2015-08-01
• First posted: 2012-04-09
• Last updated: 2014-12-23

Locations

4 sites across 1 country: Canada