A multi‐center controlled trial of growth hormone treatment in children with cystic fibrosis

Abstract

SUMMARY Objectives We evaluated safety and efficacy of recombinant human growth hormone (rhGH) for improving growth, lean body mass (LBM), pulmonary function, and exercise tolerance in children with cystic fibrosis (CF) and growth restriction. Study design Multicenter, open-label, controlled clinical trial comparing outcomes in prepubertal children < 14 years with CF, randomized in a 1:1 ratio to receive daily rhGH (Nutropin AQ) or no treatment (control) for 12 months, followed by a 6-month observation (month 18). Safety was monitored at each visit, including assessments of glucose tolerance. Results Sixty-eight subjects were randomized (control n = 32; rhGH n = 36). Mean height standard deviation score (SDS) in the rhGH group increased by 0.5 ± 0.4 at 12 months (mean ± SD, p < 0.001); the control group height SDS remained unchanged. Weight increased by 3.8 ± 1.8 vs 2.8 ± 1.5 kg, (mean ± SD, p = 0.0356) and LBM increased by 3.8 ± 1.8 vs 2.1 ± 1.4 kg (p = 0.0002) in the rhGH group vs controls, respectively. Forced vital capacity increased by 325 ± 319 in the rhGH group compared with 178 ± 152 mL in controls (mean ± SD, p = 0.032). Forced expiratory volume in 1 second improved in both groups with a significant difference between groups after adjustment for baseline severity (LSMeans ± SE: rhGH, 224 ± 37, vs controls, 108 ± 40 mL; p = 0.04). There was no difference between groups in exercise tolerance (6-minute walk distance) at 1 year. Changes in glucose tolerance for the two groups were similar over the 12-month study period, with three subjects developing IGT and one CFRD in each group. One rhGH-treated patient developed increased intracranial pressure. Conclusions Treatment with rhGH in prepubertal children with CF was effective in promoting growth, weight, LBM, lung volume, and lung flows, and had an acceptable safety profile.

Reduced bone length, growth plate thickness, bone content, and IGF-I as a model for poor growth in the CFTR-deficient rat

“…The reduced levels of serum IGF-I observed in the Cftr-/- rats may inpart contribute to the reduced volume of cells in the hypertrophic region of the growth plate. The relationship of the GH/IGF-I axis in linear growth and bone health is well established [ 28 ], and treatment with human GH (hGH) has demonstrated improved growth in CF [ 29 ]. IGF-I treatment has been utilized to improve linear growth in non-CF children [ 30 ], and improves bone density in disease states with reduced anabolic drive (such as anorexia) [ 31 ].…”

Growth and the Growth Hormone-Insulin Like Growth Factor 1 Axis in Children With Chronic Inflammation: Current Evidence, Gaps in Knowledge, and Future Directions

“…The three largest RCT of rhGH in CF all show that HV is approximately 150% higher in the rhGH treated group compared with control/placebo (422,424,425). In the study by Schnabel et al including two doses of rhGH, the "lower" dose of rhGH was comparable to the dose used by Hardin et al (424) and Stavley et al (422).…”

“…The three largest RCT of rhGH in CF all show that HV is approximately 150% higher in the rhGH treated group compared with control/placebo (422,424,425). In the study by Schnabel et al including two doses of rhGH, the "lower" dose of rhGH was comparable to the dose used by Hardin et al (424) and Stavley et al (422). In that study, height velocity in the group treated with the "higher" dose of rhGH of 0.49 mg/kg/wk was approximately 180% higher than the control group; whereas height velocity in the group treated with the "lower" dose of 0.273 mg/ kg/wk was approximately 150% higher than the control group (425) The individuals included in the RCT by Schnabel et al (425) were in mid adolescents as the inclusion criteria was bone age of 8 -18 years, whereas the studies by Hardin et al (424) and Stalvey et al (422) were younger, pre pubertal at baseline.…”

3.19 Nutrition in Cystic Fibrosis

“…While growth parameters and pulmonary function seem to improve in treated patients, the overall benefits to health cannot be determined from the moderate evidence available. One recent multicenter trial in which growth hormone was administered for 12 months to patients with reduced growth and bone age indicated its effectiveness in improving growth and lung volumes [20] . Larger trials with appropriate patient selection are needed in order to establish its safety and effectiveness.…”