GH has metabolic, but no pulmonary effect in those with cystic fibrosis

Exercise performance was linked to mortality in this patient population.

Issue: July 2007

Treatment with growth hormone did not result in any improvement in the lung function of patients with cystic fibrosis, according to results of a recent study.

Patients with cystic fibrosis often have abnormal growth rates and body weight compared with people without the disease. Data from a multicenter, randomized, double blind, placebo-controlled study have indicated that no significant effect on pulmonary function resulted from 24 weeks of GH treatment. The results of the study were published in Pediatrics.

“Growth hormone has a metabolic effect but no direct effect on lung function in patients with cystic fibrosis,” Felix Ratjen, MD, PhD, head of the division of respiratory medicine and Sellers Chair of Cystic Fibrosis at Hospital for Sick Children, Toronto, told Endocrine Today.

Due to the lack of effect on lung function, treatment probably will not be changed by these observations, Ratjen said.

Two fixed dosages

The study was designed to compare the efficacy and safety of two fixed dosages of recombinant human GH or placebo in patients with cystic fibrosis. It was conducted in 12 German cystic fibrosis centers between January 2001 and February 2004.

Patients were randomly assigned to one of three treatment arms: 0.070 mg/kg body weight per day somatropin (Genotropin, Pfizer), 0.039 mg/kg body weight per day somatropin, or placebo. After the 24-week double-blind treatment period, patients assigned to GH therapy maintained their current dosage and patients assigned placebo were assigned to either the high or low GH-dosage treatment regimen.

“Exercise performance is linked to survival in these patients,” Ratjen said. “Patients with poorer exercise tolerance die earlier; therefore, the hope was that if exercise tolerance is improved that this will also be important for a patient’s outcome.”

Compared with baseline the forced expiratory volume in one second did not change significantly for patients treated with GH. A trend existed toward an increase in absolute forced vital capacity in both the low-dose and high-dose GH treatment groups. Neither was statistically significant compared to placebo.

“These data show that you need longer studies to look at lung function decline, which may be positively affected by GH and which then would indicate that this treatment really changes the course of lung disease in these patients,” Ratjen said.

In contrast, both treatment groups had an increase in absolute oxygen uptake during treatment compared with placebo, which had no increase (P=.05 for both). During the open-label period, patients previously assigned placebo had increases in work rate and mean oxygen uptake as well.

Metabolic components

Absolute growth velocity increased in both the high- (P=.025) and low-dose (P=.018) groups. The change in height observed in the treatment group was negatively associated with age (P<.0001). During the open- label period, there was a 4.7 cm/year change in growth velocity for the entire study population.

Patients assigned GH also had a increase in IGF-I during the treatment period compared with no change in the placebo group (P<.002). IGFBP-3 increased in the treatment group (P<.05) and decreased in patients assigned placebo.

“Because the primary effects of GH in cystic fibrosis are metabolic rather than pulmonary, the potential respiratory benefits of GH treatment may not translate into short-term increases in lung function,” the researchers wrote. – by Leah Lawrence

For more information:
Schnabel D, Grasemann, Staab D, et al. A multicenter, randomized, double-blind, placebo-controlled trial to evaluate the metabolic and respiratory effects of growth hormone in children with cystic fibrosis. Pediatrics. 2007;119:1230-1238.