Intestinal FailurePhase 1/2GLP-2-01NCT01573286

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

A Phase 1/2 study testing Glucagon-Like Peptide 2 and Glucagon like peptide-2 in people with Intestinal Failure and Short Bowel Syndrome, run by Alberta Children's Hospital at 4 sites in Canada.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages Up to 18 years
Conditions the study is for: Intestinal Failure, Short Bowel Syndrome
What is being tested?: Glucagon-Like Peptide 2 and Glucagon like peptide-2
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 13 participants
Where: 4 sitesCanada
Study dates: Jan 2012to Aug 2015
Phase: Phase 1/2
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages Up to 18 years
All sexes
No healthy volunteers
Child, Adult

Who may be able to join

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.

Who cannot join

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.

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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.

Trial locations and contacts

4 sites in 1 country.

Canada4 sites

Alberta Children's Hospital
Calgary, Alberta, T3B 6A8
Stollery Children's Hospital
Edmonton, Alberta, T6G 2C8
Hospital for Sick Children
Toronto, Ontario, M5G 1X8
British Columbia Children's Hospital
Vancouver, British Columbia, V6H 3V4

Other trials in Canada

About this study

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

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.

Read the 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
Being tested: Glucagon-Like Peptide 2, Glucagon like peptide-2
Keywords: Infant Nutrition Disorders, Childhood nutrition disorders, malnutrition, post surgical syndromes, necrotising enterocolitis, intestinal atresia, gastroschisis
Medical subject headings: Intestinal Failure, Short Bowel Syndrome, Infant Nutrition Disorders, Malnutrition, Enterocolitis, Necrotizing, Intestinal Atresia, Gastroschisis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Glucagon-Like Peptide 2Drug
Also called Glucagon-like peptide-2 (Lot: IC-115) Mfg. University of Calgary
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.
Glucagon like peptide-2Drug
Also called Glucagon-like peptide-2 (Lot: IC-115) Mfg. University of Calgary
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.

Study groups in NCT01573286
Study group	Role	What they receive
Intestinal Failure in children (>1 year)	Experimental	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 Receives: Drug: Glucagon-Like Peptide 2
GLP-2 in Infants (<1 year of age)	Experimental	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. Receives: Drug: Glucagon like peptide-2

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: Done on Day 3 and 42

Secondary outcomes (6)

Changes in the Enteral Caloric intake
During active drug administration, changes in the proportion of total enteral calories tolerated (Including discontinuation of parenteral nutrition) will be monitored twice weekly (hospital inpatients) and weekly (for outpatients). Following the phase of active treatment, patients will be followed at 1, 6, and 12 months.
Measured: one year
Nutritional Parameters
During the phase of active treatment, nutritional parameters; weight gain, maintenance of growth (z scores), Liver function, albumin, protein levels, C-reactive protein, electrolytes, renal function (creatinine levels) will be monitored twice weekly (hospital inpatients) and weekly (for outpatients). Following the phase of active treatment, patients will be followed at 1, 6, and 12 months.
Measured: one year
Mucosal Morphology
If procedures requiring sedation or surgery are done during the phase of active drug administration, intestinal biopsies will be requested, to quantify changes in crypt cell proliferation and apoptosis index, and intestinal morphology (villus height and/or crypt depth) between pre-treatment surgical samples, and specimens obtained while under treatment.
Measured: 6 weeks
Intrinsic GLP-2 Production
At the beginning of the active treatment, and during week 5, intrinsic meal stimulated GLP-2 production will be assessed. During followup, these values will be assessed at 1,6 and 12 months post-treatment
Measured: One year
Septic Episodes
During the treatment phase, the number of septic episodes, and the type of infecting organisms will be recorded.
Measured: 6 weeks
Serum Citrulline Levels
Citrulline levels as a measure of intestinal mucosal mass will be assessed at time 0, and on the last day of active treatment. During followup, these values will be assessed at 1,6 and 12 months post-treatment
Measured: One year.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 2012Aug 2015

First posted9 Apr 2012 (estimated)
Study startJan 2012
Primary completionAug 2014
Study completionAug 2015 (estimated)

Why it stopped: GLP-2 Drug product stability concerns

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Intestinal FailureStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 13 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01573286
Sponsor's protocol ID: GLP-2-01
Other IDs: 150979
Acronym: GLP-2-01
Status last verified: Dec 2014
First submitted: 5 Apr 2012
Last updated: 23 Dec 2014
Results posted: No
Data monitoring committee: Yes

Publications

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.
PubMed 24368164
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

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 23 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase 1-2 Trial of Glucagon-like Peptide 2 (GLP-2) in Infants and Children With Intestinal Failure
ClinicalTrials.gov ID: NCT01573286
Acronym / sponsor ID: GLP-2-01 / GLP-2-01
Conditions: Intestinal Failure, Short Bowel Syndrome
Keywords: Infant Nutrition Disorders, Childhood nutrition disorders, malnutrition, post surgical syndromes, necrotising enterocolitis, intestinal atresia, gastroschisis
Phase: Phase 1/2
Study type: Interventional
Recruitment status: TerminatedReason stopped: GLP-2 Drug product stability concerns
Enrolment: 13 participants (actual)
Lead sponsor: Alberta Children's HospitalUniversity, hospital or other
Collaborators: Stollery Children's Hospital, The Hospital for Sick Children, British Columbia Children's Hospital
Study start: Jan 2012
Primary completion: Aug 2014 (actual)
Study completion: Aug 2015 (estimated)
First posted: 9 Apr 2012 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Infants will be allocated sequentially to a group (n = 6 per group) treated with GLP-2 at 5,10, or 20 μg/kg/day.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Intestinal Failure in children (>1 year)	Experimental	Drug: Glucagon-Like Peptide 2Children 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)	Experimental	Drug: Glucagon like peptide-2Infants 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.

Who may qualify

Ages: Up to 18 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult

Key inclusion criteria (3 listed)

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.

Key exclusion criteria (11 listed)

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;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Glucagon-Like Peptide 2Also: Glucagon-like peptide-2 (Lot: IC-115) Mfg. University of CalgaryPatients 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	Intestinal Failure in children (>1 year)
Glucagon like peptide-2Also: Glucagon-like peptide-2 (Lot: IC-115) Mfg. University of CalgaryPatients 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.	Drug	GLP-2 in Infants (<1 year of age)

Primary outcome

Frequency of Adverse events
Time frame: One year
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.
Pharmacokinetics (Peak serum level. Area under the curve
Time frame: Done on Day 3 and 42
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.

6 secondary outcomes

Changes in the Enteral Caloric intake
Time frame: one year
Nutritional Parameters
Time frame: one year
Mucosal Morphology
Time frame: 6 weeks
Intrinsic GLP-2 Production
Time frame: One year
Septic Episodes
Time frame: 6 weeks
Serum Citrulline Levels
Time frame: One year.

Results and safety

The study was stopped early (reason given: GLP-2 Drug product stability concerns). Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 23 Dec 2014.
Background: PubMed 24368164Sigalet 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.
Results publicationSigalet 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

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

David Sigalet, MD PhD study director

Alberta Children's Hospital

4 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Glucagon-Like Peptide 2 and Glucagon like peptide-2 in people with Intestinal Failure and Short Bowel Syndrome, run by Alberta Children's Hospital at 4 sites in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 23 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: GLP-2 Drug product stability concerns). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Frequency of Adverse events (time frame: One year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01573286, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Dec 2014.