Safety and Dosing Study of Glucagon-Like Peptide 2 in Children With Intestinal Failure

Research output: Contribution to journalJournal articleResearchpeer-review

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Safety and Dosing Study of Glucagon-Like Peptide 2 in Children With Intestinal Failure. / Sigalet, David L; Brindle, Mary; Boctor, Dana; Casey, Linda; Dicken, Bryan; Butterworth, Sonia; Lam, Viona; Karnik, Vikram; de Heuvel, Elaine; Hartmann, Bolette; Holst, Jens.

In: Journal of Parenteral and Enteral Nutrition, Vol. 41, No. 5, 2017, p. 844-852.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Sigalet, DL, Brindle, M, Boctor, D, Casey, L, Dicken, B, Butterworth, S, Lam, V, Karnik, V, de Heuvel, E, Hartmann, B & Holst, J 2017, 'Safety and Dosing Study of Glucagon-Like Peptide 2 in Children With Intestinal Failure', Journal of Parenteral and Enteral Nutrition, vol. 41, no. 5, pp. 844-852. https://doi.org/10.1177/0148607115609566

APA

Sigalet, D. L., Brindle, M., Boctor, D., Casey, L., Dicken, B., Butterworth, S., ... Holst, J. (2017). Safety and Dosing Study of Glucagon-Like Peptide 2 in Children With Intestinal Failure. Journal of Parenteral and Enteral Nutrition, 41(5), 844-852. https://doi.org/10.1177/0148607115609566

Vancouver

Sigalet DL, Brindle M, Boctor D, Casey L, Dicken B, Butterworth S et al. Safety and Dosing Study of Glucagon-Like Peptide 2 in Children With Intestinal Failure. Journal of Parenteral and Enteral Nutrition. 2017;41(5):844-852. https://doi.org/10.1177/0148607115609566

Author

Sigalet, David L ; Brindle, Mary ; Boctor, Dana ; Casey, Linda ; Dicken, Bryan ; Butterworth, Sonia ; Lam, Viona ; Karnik, Vikram ; de Heuvel, Elaine ; Hartmann, Bolette ; Holst, Jens. / Safety and Dosing Study of Glucagon-Like Peptide 2 in Children With Intestinal Failure. In: Journal of Parenteral and Enteral Nutrition. 2017 ; Vol. 41, No. 5. pp. 844-852.

Bibtex

@article{2eee8c801352491ea4ee146e126a8c4e,
title = "Safety and Dosing Study of Glucagon-Like Peptide 2 in Children With Intestinal Failure",
abstract = "BACKGROUND AND AIMS: A glucagon-like peptide 2 (GLP-2) analogue is approved for adults with intestinal failure, but no studies of GLP-2 have included children. This study examined the pharmacokinetics, safety, and nutritional effects of GLP-2 in children with intestinal failure.METHODS: Native human GLP-2(1-33) was synthesized following good manufacturing practices. In an open-label trial, with parental consent, 7 parenteral nutrition-dependent pediatric patients were treated with subcutaneous GLP-2 (20 µg/kg/d) for 3 days (phase 1) and, if tolerated, continued for 42 days (phase 2). Nutritional treatment was directed by the primary caregivers. Patients were followed to 1 year.RESULTS: Seven patients were enrolled (age: 4.0 ± 0.8 years; bowel length, mean ± SEM: 24{\%} ± 4{\%} of predicted). All were parenteral nutrition dependent since birth, receiving 44{\%} ± 5{\%} of calories by parenteral nutrition. GLP-2 treatment had no effect on vital signs (blood pressure, heart rate, and temperature) and caused no significant adverse events. Peak GLP-2 levels were 380 pM (day 3) and 295 pM (day 42), with no change in half-life or endogenous GLP-2 levels. Nutritional indices showed a numeric improvement in Z scores and citrulline levels; the Z score was maintained while citrulline levels returned to baseline once GLP-2 was discontinued.CONCLUSIONS: GLP-2 was well tolerated in children, with a pharmacokinetic profile similar to that of adults. There were no changes in endogenous GLP-2 release or metabolism. These results suggest that GLP-2 ligands may be safely used in pediatric patients; larger trials are suggested to investigate nutritional effects.",
author = "Sigalet, {David L} and Mary Brindle and Dana Boctor and Linda Casey and Bryan Dicken and Sonia Butterworth and Viona Lam and Vikram Karnik and {de Heuvel}, Elaine and Bolette Hartmann and Jens Holst",
note = "{\circledC} 2015 American Society for Parenteral and Enteral Nutrition.",
year = "2017",
doi = "10.1177/0148607115609566",
language = "English",
volume = "41",
pages = "844--852",
journal = "Journal of Parenteral and Enteral Nutrition",
issn = "0148-6071",
publisher = "SAGE Publications",
number = "5",

}

RIS

TY - JOUR

T1 - Safety and Dosing Study of Glucagon-Like Peptide 2 in Children With Intestinal Failure

AU - Sigalet, David L

AU - Brindle, Mary

AU - Boctor, Dana

AU - Casey, Linda

AU - Dicken, Bryan

AU - Butterworth, Sonia

AU - Lam, Viona

AU - Karnik, Vikram

AU - de Heuvel, Elaine

AU - Hartmann, Bolette

AU - Holst, Jens

N1 - © 2015 American Society for Parenteral and Enteral Nutrition.

PY - 2017

Y1 - 2017

N2 - BACKGROUND AND AIMS: A glucagon-like peptide 2 (GLP-2) analogue is approved for adults with intestinal failure, but no studies of GLP-2 have included children. This study examined the pharmacokinetics, safety, and nutritional effects of GLP-2 in children with intestinal failure.METHODS: Native human GLP-2(1-33) was synthesized following good manufacturing practices. In an open-label trial, with parental consent, 7 parenteral nutrition-dependent pediatric patients were treated with subcutaneous GLP-2 (20 µg/kg/d) for 3 days (phase 1) and, if tolerated, continued for 42 days (phase 2). Nutritional treatment was directed by the primary caregivers. Patients were followed to 1 year.RESULTS: Seven patients were enrolled (age: 4.0 ± 0.8 years; bowel length, mean ± SEM: 24% ± 4% of predicted). All were parenteral nutrition dependent since birth, receiving 44% ± 5% of calories by parenteral nutrition. GLP-2 treatment had no effect on vital signs (blood pressure, heart rate, and temperature) and caused no significant adverse events. Peak GLP-2 levels were 380 pM (day 3) and 295 pM (day 42), with no change in half-life or endogenous GLP-2 levels. Nutritional indices showed a numeric improvement in Z scores and citrulline levels; the Z score was maintained while citrulline levels returned to baseline once GLP-2 was discontinued.CONCLUSIONS: GLP-2 was well tolerated in children, with a pharmacokinetic profile similar to that of adults. There were no changes in endogenous GLP-2 release or metabolism. These results suggest that GLP-2 ligands may be safely used in pediatric patients; larger trials are suggested to investigate nutritional effects.

AB - BACKGROUND AND AIMS: A glucagon-like peptide 2 (GLP-2) analogue is approved for adults with intestinal failure, but no studies of GLP-2 have included children. This study examined the pharmacokinetics, safety, and nutritional effects of GLP-2 in children with intestinal failure.METHODS: Native human GLP-2(1-33) was synthesized following good manufacturing practices. In an open-label trial, with parental consent, 7 parenteral nutrition-dependent pediatric patients were treated with subcutaneous GLP-2 (20 µg/kg/d) for 3 days (phase 1) and, if tolerated, continued for 42 days (phase 2). Nutritional treatment was directed by the primary caregivers. Patients were followed to 1 year.RESULTS: Seven patients were enrolled (age: 4.0 ± 0.8 years; bowel length, mean ± SEM: 24% ± 4% of predicted). All were parenteral nutrition dependent since birth, receiving 44% ± 5% of calories by parenteral nutrition. GLP-2 treatment had no effect on vital signs (blood pressure, heart rate, and temperature) and caused no significant adverse events. Peak GLP-2 levels were 380 pM (day 3) and 295 pM (day 42), with no change in half-life or endogenous GLP-2 levels. Nutritional indices showed a numeric improvement in Z scores and citrulline levels; the Z score was maintained while citrulline levels returned to baseline once GLP-2 was discontinued.CONCLUSIONS: GLP-2 was well tolerated in children, with a pharmacokinetic profile similar to that of adults. There were no changes in endogenous GLP-2 release or metabolism. These results suggest that GLP-2 ligands may be safely used in pediatric patients; larger trials are suggested to investigate nutritional effects.

U2 - 10.1177/0148607115609566

DO - 10.1177/0148607115609566

M3 - Journal article

C2 - 26471991

VL - 41

SP - 844

EP - 852

JO - Journal of Parenteral and Enteral Nutrition

JF - Journal of Parenteral and Enteral Nutrition

SN - 0148-6071

IS - 5

ER -

ID: 150706402