Growth Hormone Deficiency in Adult Prader-Willi Syndrome Patients: Preliminary Findings from a 4-site Study of Genotropin Treatment

 Harriette Mogul¹, Michael Frey¹,  Barbara Y. Whitman², Susan E. Myers², Phillip D.K. Lee³, William Zipf⁴, Belinda Pinyard⁴

¹Medical College of New York, Valhalla, NY; ²Department of Pediatrics, St. Louis University School of Medicine, 1465 S. Grand, St. Louis, MO 63104; ³University of California at Los Angeles, Los Angeles, CA; ⁴Columbus,Ohio. 

 Introduction: Growth hormone (GH) replacement with Genotropin is currently approved for children with Prader-Willi syndrome (PWS) with demonstrable growth failure. Additionally, GH replacement is approved for adult patients with documented growth hormone deficiency (GHD) including GH deficient PWS subjects. Studies of GH replacement in children and adolescents with PWS suggest that GH replacement may have important health benefits for affected adults, but GH replacement has not been studied in this adult population. Accordingly, we are conducting a multi-center, open label 12-month trial to evaluate dose optimization,  safety and efficacy of Genotropin® in GHD adults with PWS and to compare these findings to other GHD adults.

 Methods: A total of 40 subjects will be enrolled at four sites.  Inclusion criteria include: (1) molecular diagnosis of PWS, (2) age > 18 years, (3) naïve to or off GH replacement for 12 months, (4) basal IGF-1 < 1 S.D. for age and gender, (5) ability to participate in a clinical trial of injectables, and (6) evidence of dietary control of weight gain. Exclusion criteria include: (1) major systemic illness including congestive heart failure at or greater than stage 3, (2) severe mental retardation precluding cooperation, (3) active malignancy, (4) poorly controlled Type 2 diabetes (Hgb A1_C =>8%), (5) evidence of retinopathy, and (6) previous allergic reaction to GH or carrier.

 Results and Discussion: This initial report will summarize preliminary study findings in 23 subjects.  Baseline studies included glucose tolerance tests with insulin levels, EKG, ECHO and carotid imaging studies and DEXA for body composition and bone density. Quality of life and behavioral characteristics were measured at baseline and regular study intervals. Twenty-two subjects met study criteria for growth hormone deficiency based on a peak GH of less than 5 ng/dl after provocative stimulation with L-dopa.

 Mean baseline characteristics of the study population included age 30.1 (s.e. 2.1) years, peak growth hormone level of 2.5 ng/ml (s.e. = .60 ng/ml, norm >=5 ng/ml); and IGF-1 level of 118 ng/ml,

(-1SD for age and gender for all subjects). Genotropin was initiated at a dose of 0.2 mg daily, with monthly increments of 0.2 mg until IGF-1 levels were maintained between 0 and + 2SD for age and gender at  for two successive months without side effects.

 Growth hormone replacement was well tolerated by all study subjects with no reported emergent adverse events. Most adults, including those in group homes, were able to administer their own injections with supervision. An illustrative case example including lab values and anthropometrics will be presented. Results from this study will provide detailed information on the efficacy and safety of short-term GH treatment in GH deficient adults with PWS.

July 2003