Treatment with growth hormone-releasing hormone (GHRH) 1-44 in children with idiopathic growth hormone deficiency: a randomized double-blind dose-effect study. The GHRH European Multicenter Study (GEMS) Group.
One hundred and eleven pre-pubertal children (70 boys, 41 girls, aged 2.5 to 14.3 years) with growth failure (height 2 SD below the mean for chronological age (CA) and height velocity (HV) below the 10th percentile for bone age) due to idiopathic growth hormone deficiency (peak plasma GH < 20 mUI/1 to two standard provocative tests) were treated with GHRH 1-44 NH2. Patient stratification in two classes was performed according to body weight; in each class, patients were randomly allocated to one of seven GHRH doses, from 30 to 300 micrograms/day. GHRH was injected subcutaneously, every evening, for six months in a double-blind fashion. No relationship was found between the absolute or incremental HV during treatment and the dose (range from 1.3-23.1 micrograms/kg/day) of GHRH. However, HV (cm/year) increased from 3.8 +/- 0.1 (mean +/- SEM) before treatment to 6 +/- 0.2 during six months treatment and 47 patients (42%) increased their HV up to at least the mean normal HV for bone age (catch-up growth). Low titer antibodies to GHRH were found in 19 patients (17.1%) at six months; no adverse effect was observed. Our results suggest that patients showing catch-up growth were older, had a height closer to the mean for chronological age and a slower pre-treatment height velocity. Failure to demonstrate a relationship between GHRH dose and changes in growth velocity might be explained by the combination of a placebo effect, insufficient frequency of GHRH administration and heterogeneity of the population.
Lievre
M
M
Unité de Pharmacologie Clinique, Lyon, France.
Chatelain
P
P
Van Vliet
G
G
Olivier
M
M
Blanchard
J
J
Morre
M
M
Boissel
J P
JP
D000293:Adolescent; D001827:Body Height / Q000187:drug effects*; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D013006:Growth Hormone / Q000172:deficiency*; D013007:Growth Hormone-Releasing Hormone / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D010187:Pancreatic Hormones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010349:Patient Compliance; D010446:Peptide Fragments / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D010187:Pancreatic Hormones; D010446:Peptide Fragments; C040786:somatotropin releasing hormone (1-44)amide; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone