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

NCT ID: NCT01573286

Last Updated: 2014-12-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

13 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-01-31

Study Completion Date

2015-08-31

Brief Summary

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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

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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

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Intestinal Failure Short Bowel Syndrome

Keywords

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Infant Nutrition Disorders Childhood nutrition disorders malnutrition post surgical syndromes necrotising enterocolitis intestinal atresia gastroschisis

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Intestinal Failure in children (>1 year)

Children 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

Group Type EXPERIMENTAL

Glucagon-Like Peptide 2

Intervention Type DRUG

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.

GLP-2 in Infants (<1 year of age)

Infants 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.

Group Type EXPERIMENTAL

Glucagon like peptide-2

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type 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.

Intervention Type DRUG

Other Intervention Names

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Glucagon-like peptide-2 (Lot: IC-115) Mfg. University of Calgary Glucagon-like peptide-2 (Lot: IC-115) Mfg. University of Calgary

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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.
* Absorptive defects (such as microvillus inclusion disease)
* 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.
Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Stollery Children's Hospital

OTHER

Sponsor Role collaborator

The Hospital for Sick Children

OTHER

Sponsor Role collaborator

British Columbia Children's Hospital

OTHER

Sponsor Role collaborator

Alberta Children's Hospital

OTHER

Sponsor Role lead

Responsible Party

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David Sigalet MD PhD

Adjunct Professor, Division of Pediatric Surgery

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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David Sigalet, MD PhD

Role: STUDY_DIRECTOR

Alberta Children's Hospital

Locations

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Alberta Children's Hospital

Calgary, Alberta, Canada

Site Status

Stollery Children's Hospital

Edmonton, Alberta, Canada

Site Status

British Columbia Children's Hospital

Vancouver, British Columbia, Canada

Site Status

Hospital for Sick Children

Toronto, Ontario, Canada

Site Status

Countries

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Canada

References

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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.

Reference Type BACKGROUND
PMID: 24368164 (View on PubMed)

Sigalet 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

Reference Type RESULT

Other Identifiers

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150979

Identifier Type: OTHER

Identifier Source: secondary_id

GLP-2-01

Identifier Type: -

Identifier Source: org_study_id