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- Hansen-Pupp, Ingrid, et al.
(författare)
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Continuous longitudinal infusion of rhIGF-1/rhIGFBP-3 in extremely preterm infants: Evaluation of feasibility in a phase II study
- 2017
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Ingår i: Growth Hormone and IGF Research. - : Elsevier BV. - 1096-6374. ; 36, s. 44-51
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Tidskriftsartikel (refereegranskat)abstract
- Objective To evaluate the feasibility of continuous longitudinal intravenous infusion of recombinant human insulin-like growth factor-1/recombinant human insulin-like growth factor binding protein-3 (rhIGF-1/rhIGFBP-3) for prevention of retinopathy of prematurity and other complications in extremely preterm infants (< 28 weeks' gestational age), based on initial sections of a phase II randomized controlled trial. Design The phase II trial was designed in four sections (A–D); we report pharmacokinetic and adverse events (AEs) data pooled for Sections B and C. Infants in these study sections received rhIGF-1/rhIGFBP-3 or standard neonatal care up to postmenstrual age (weeks + days) 28 + 6 (Section B) or 29 + 6 (Section C). Dosing was variable/individualized and intended to establish serum IGF-1 within physiological intrauterine levels. Results Nineteen infants were enrolled across Sections B/C: nine received rhIGF-1/rhIGFBP-3 and 10 standard neonatal care. Among the nine infants treated with study drug, mean (SD) dose was 95.1 (10.6) μg/kg/day and mean (SD) duration of infusion was 14.2 (6.1) days. Eight of nine (88.9%) treated infants had two or more dose changes during treatment. Mean serum IGF-1 levels during treatment were 23 μg/L among treated infants compared with 14 μg/L in control infants. Overall, 66.3% of IGF-1 measurements for treated infants were within target levels (20–60 μg/L) versus 17.3% for control infants. Overall incidence of adverse events (AEs) was similar for treated versus control infants; AEs were generally as expected in this population, and no AEs were considered related to study treatment. There was no observed increase in infection rates (considered a possible risk with continuous intravenous infusion) between treated and control infants. Rates of hypoglycemia (considered a possible risk with IGF-1 treatment) were also similar between groups. There was one fatal serious AE of cardiac tamponade in the treated group (not considered treatment related). Conclusion Infusion of rhIGF-1/rhIGFBP-3 increased serum concentrations of IGF-1 and attainment of target levels relative to standard neonatal care. rhIGF-1/rhIGFBP-3 infusion was well tolerated with no safety signals. Although further work is required to optimize the dose regimen for attainment of physiological intrauterine levels, we believe the results reported support the feasibility of rhIGF-1/rhIGFBP-3 continuous longitudinal infusion in extremely preterm infants. The trial is registered at ClinicalTrials.gov (NCT01096784). © 2017 The Authors
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- Hellgren, Gunnel, 1961, et al.
(författare)
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The growth hormone receptor exon 3-deleted/full-length polymorphism and response to growth hormone therapy in prepubertal idiopathic short children
- 2015
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Ingår i: Growth Hormone & IGF Research. - : Elsevier BV. - 1096-6374 .- 1532-2238. ; 25:3, s. 127-135
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The primary aim of the study was to evaluate d3-GHR as a possible cause of increased GH sensitivity in children with delayed infancy-childhood transition (DICT). The secondary aim was to investigate the impact of the GHR exon 3 deleted/full-length (d3/f1) polymorphism on GH treatment response in prepubertal children classified as having idiopathic short stature (ISS). Design: Study subjects included 167 prepubescent longitudinally followed children classified as having ISS. Children were randomized to standard-dose GH treatment (33 mu g kg(-1) day(-1)), to double-dose treatment (67 mu g kg(-1) day(-1)), or to an untreated control group. Growth and metabolic outcome were evaluated at birth (n = 166), after one year of treatment (n = 59) and at adult height (n = 145). Genotyping of the GHR d3/f1 polymorphism was performed using TaqMan SNP genotyping of tagSNP rs6873545. Results: Birth and early growth data did not reach the predetermined level of statistical significance for difference between genotypes. Growth and IGF-1 response after one year of GH treatment did not differ between genotypes. IGFBP-3(SDS) was higher in untreated d3-GHR carriers than in untreated fl/fl individuals, whereas there was insufficient evidence for higher IGFBP-3(SDS) in treated d3-GHR carriers. Genotype did not explain the growth response to treatment, and no differences in height(SDS), height gain, or difference in height to midparental height(SDS) between genotype groups were found at adult height. Conclusion: The common GHR d3/fl polymorphism is probably not a cause of DICT in children with ISS, and our results do not suggest that the d3-GHR genotype is associated with increased sensitivity to GH in children with ISS.
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- Hellström, Ann, 1959, et al.
(författare)
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IGF-I in the clinics: Use in retinopathy of prematurity
- 2016
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Ingår i: Growth Hormone & Igf Research. - : Elsevier BV. - 1096-6374. ; 30-31, s. 75-80
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Tidskriftsartikel (refereegranskat)abstract
- Retinopathy of prematurity is a potentially blinding disease, which is associated with low neonatal IGF-I serum concentrations and poor growth. In severe cases impaired retinal vessel growth is followed by pathologic neovascularization, which may lead to retinal detachment. IGF-I may promote growth even in catabolic states. Treating preterm infants with recombinant human (rh) IGF-I to concentrations normally found during gestation has been suggested to have a preventative effect on ROP. A recent phase 2 study treating infants (gestational age between 23 weeks + 0 days and 27 weeks +6 days) with rhIGF-I/IGF binding protein-3 until 30 postmenstrual weeks showed no effect on ROP but a 53% reduction in severe bronchopulmonary dysplasia and 44% reduction in severe intraventricular hemorrhage. Oxygen is a major risk factor for ROP and during the phase 2 study oxygen saturation targets were increased to 90-95%, due to national guidelines, which might have affected ROP rate and severity making increased IGF-I a weaker preventative factor for ROP.
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- Hoybye, C, et al.
(författare)
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Status of long-acting-growth hormone preparations--2015
- 2015
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Ingår i: Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society. - : Elsevier BV. - 1532-2238. ; 25:5, s. 201-206
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Tidskriftsartikel (refereegranskat)
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