Intranasal GHRP-2 Spray Fails to Promote Growth in Children with Growth Hormone Deficiency Despite Increasing GH Secretion
Background
Growth Hormone Deficiency (GHD) in children leads to impaired growth and short stature. Standard treatment involves injections of recombinant human Growth Hormone (GH), which can be burdensome. GH-releasing peptides (GHRPs) like GHRP-2 are potent GH secretagogues, meaning they stimulate the body's own pituitary gland to release GH. The hypothesis was that stimulating this endogenous GH secretion through a more convenient intranasal spray could offer a viable alternative to GH injections for promoting growth. This study aimed to determine if transient increases in endogenous GH, stimulated by nasally administered GHRP-2, could translate into clinically meaningful improvements in height for prepubertal children diagnosed with GHD.
Study Design
This double-blind, placebo-controlled study enrolled 126 prepubertal short children with diagnosed GHD. They were divided into three groups: placebo (P group, n=44), low-dose GHRP-2 (L group, n=41), and high-dose GHRP-2 (H group, n=41). The intervention was an intranasal spray administered twice daily for 48 weeks. Dosing was weight-based: for children <20 kg, the doses were placebo, 50 µg GHRP-2, or 100 µg GHRP-2; for children ≥20 kg, doses were placebo, 100 µg GHRP-2, or 200 µg GHRP-2. The primary endpoint was the change in height standard deviation (SD) score over the treatment period.
Results
After 48 weeks of continuous treatment, intranasal GHRP-2 did not promote growth compared to placebo. The mean change in height SD scores was not significantly different among the three groups. The placebo group showed a change of +0.07 SD, the low-dose GHRP-2 group showed a change of +0.03 SD, and the high-dose GHRP-2 group showed a change of +0.02 SD. Of the initial 126 subjects, 44 in the placebo group, 40 in the low-dose group, and 40 in the high-dose group completed the full study duration. Furthermore, no significant changes in blood IGF-I levels, a key mediator of GH's growth effects, were observed from baseline to the end of the study in any group.
The changes in the mean height SD scores after 48 wk of treatment in the P, L and H groups were 0.07 SD, 0.03 SD, and 0.02 SD, respectively, and thus no significant differences was observed among the 3 groups.
The authors speculate that the transient nature of the GH spike induced by the intranasal spray results in an area under the curve (AUC) of serum GH concentration that is too small to produce the necessary biological effects for sustained growth promotion.
Key Findings
- After 48 weeks, the change in height SD score was +0.07 in the placebo group, +0.03 in the low-dose GHRP-2 group, and +0.02 in the high-dose group.
- No significant differences in height improvement were observed among the placebo, low-dose, and high-dose GHRP-2 groups.
- The study involved 126 prepubertal children with GHD, with 124 completing the 48-week treatment period.
- Blood IGF-I levels showed no significant changes from baseline to 48 weeks in any of the three treatment arms.
- The study concludes that a transient increase in endogenous GH secretion via GHRP-2 spray does not promote growth in GHD patients.
Why It Matters
This study demonstrates a critical nuance in GH secretagogue therapy: simply stimulating a transient pulse of endogenous GH may not be sufficient to drive meaningful clinical outcomes like growth in GHD patients. For individuals or clinicians considering GHRP-2 or similar peptides for growth, this suggests that the delivery method and resulting pharmacokinetic profile are paramount. The lack of effect, even with a potent secretagogue, implies that the sustained elevation of GH and IGF-I levels achieved through standard GH injections is likely necessary for anabolic effects. Therefore, intranasal GHRP-2, despite its convenience, is not a viable substitute for GH therapy in treating GHD. The findings highlight that the total exposure (AUC) to growth hormone, not just the peak concentration, is the critical factor for promoting linear growth, a key consideration for designing future secretagogue protocols.
