Safety and Dosing Study of Glucagon-Like Peptide 2 in Children With Intestinal Failure
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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.
I: Journal of Parenteral and Enteral Nutrition, Bind 41, Nr. 5, 2017, s. 844-852.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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