Clinical trial NCT01088412: Observational Study of Somatropin Treatment in Children
Official title: The Genetics and Neuroendocrinology of Short Stature International Study (GeNeSIS)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Growth Hormone (GH) Deficiency
Short Stature Homeobox Containing Gene (SHOX) Deficiency
SHOX Deficiency-related Disorder
Non-GH-deficient Growth Disorders
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2010-03-17
Enrollment: 22845
Sex: ALL
Minimum age (years): 1
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Clinics and private practices

Brief summary: GeNeSIS is an open-label, multinational, multicenter, observational study to evaluate the safety and effectiveness of Humatrope treatment.

GeNeSIS is a modular program that includes:

* Core study: Evaluating the safety and effectiveness of Humatrope in the observational setting
* Genetic Analysis Sub-study: Investigating the genetic defects underlying growth hormone (GH) deficiency and non-GH-deficient growth disorders
* Growth Prediction Sub-study: Working to validate and refine specific models to accurately predict growth response to GH
* Short Stature Homeobox containing gene (SHOX) Deficiency Sub-study: Elucidating the clinical, endocrine and radiological features of participants with SHOX deficiency due to loss of, or mutation in the SHOX gene (including participants with Turner syndrome)
* Neoplasia Sub-study: To characterize the natural history of neoplastic disease, especially in relation to recurrence/progression of primary neoplasia or development of secondary neoplasia in children with a history of neoplasia


Eligibility criteria: Inclusion Criteria:

All participants participating in GeNeSIS must be enrolled in the core study. Participants for whom written consent to release information is provided may enter the core study if they meet any of the following inclusion guidelines:

* Treatment with Humatrope for improvement of growth.
* No treatment with somatropin in participants with a history of neoplasia or in those with any SHOX deficiency-related disorder.

Exclusion Criteria:

* Participants with closed epiphyses are not eligible for GeNeSIS entry. However, participants may remain in the study if epiphyseal closure occurs during study participation.

Primary outcomes:
measure: Type 2 Diabetes Mellitus in GH-treated Participants
timeFrame: Year 15
measure: Primary Malignancies in Participant Without Previous Cancer History
timeFrame: Year 15
measure: Final Height (FH) Gain by Diagnostic Group
timeFrame: Baseline through Year 15
Secondary outcomes:
measure: Percentage of Participants With Defects in Genes Associated With Pituitary Development
timeFrame: Baseline through Year 15
measure: Predicted First Year Height Gain Versus Actual First Year Height Gain
timeFrame: Baseline through Year 15
measure: Change From Baseline to Final Height in Anthropometric Measures for Participants With SHOX Deficiency
timeFrame: Baseline, Year 15
measure: Percentage of Participants With Recurrent Neoplasms and Second Neoplasms in Childhood Cancer Survivors
timeFrame: Baseline through Year 15
measure: Percentage of Participants With De Novo Neoplasms
timeFrame: Baseline through Year 15
measure: Diabetes Mellitus (DM) in Somatropin-Treated Children With Different Short Stature Diagnoses
timeFrame: Baseline through Year 15
Other outcomes:
Locations:
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon-Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References:
citation: Child CJ, Zimmermann AG, Chrousos GP, Cummings E, Deal CL, Hasegawa T, Jia N, Lawrence S, Linglart A, Loche S, Maghnie M, Perez Sanchez J, Polak M, Predieri B, Richter-Unruh A, Rosenfeld RG, Yeste D, Yorifuji T, Blum WF. Safety Outcomes During Pediatric GH Therapy: Final Results From the Prospective GeNeSIS Observational Program. J Clin Endocrinol Metab. 2019 Feb 1;104(2):379-389. doi: 10.1210/jc.2018-01189.
citation: Deal C, Kirsch S, Chanoine JP, Lawrence S, Cummings E, Rosolowsky ET, Marks SD, Jia N, Child CJ; GeNeSIS National Board on behalf of the GeNeSIS Canada Investigators. Growth hormone treatment of Canadian children: results from the GeNeSIS phase IV prospective observational study. CMAJ Open. 2018 Sep 10;6(3):E372-E383. doi: 10.9778/cmajo.20180020. Print 2018 Jul-Sep.
citation: Quigley CA, Child CJ, Zimmermann AG, Rosenfeld RG, Robison LL, Blum WF. Mortality in Children Receiving Growth Hormone Treatment of Growth Disorders: Data From the Genetics and Neuroendocrinology of Short Stature International Study. J Clin Endocrinol Metab. 2017 Sep 1;102(9):3195-3205. doi: 10.1210/jc.2017-00214.
citation: Blum WF, Deal C, Zimmermann AG, Shavrikova EP, Child CJ, Quigley CA, Drop SL, Cutler GB Jr, Rosenfeld RG. Development of additional pituitary hormone deficiencies in pediatric patients originally diagnosed with idiopathic isolated GH deficiency. Eur J Endocrinol. 2013 Nov 22;170(1):13-21. doi: 10.1530/EJE-13-0643. Print 2014 Jan.
citation: Deal C, Hasselmann C, Pfaffle RW, Zimmermann AG, Quigley CA, Child CJ, Shavrikova EP, Cutler GB Jr, Blum WF. Associations between pituitary imaging abnormalities and clinical and biochemical phenotypes in children with congenital growth hormone deficiency: data from an international observational study. Horm Res Paediatr. 2013;79(5):283-92. doi: 10.1159/000350829. Epub 2013 May 16.
citation: Child CJ, Zimmermann AG, Scott RS, Cutler GB Jr, Battelino T, Blum WF; GeNeSIS International Advisory Board. Prevalence and incidence of diabetes mellitus in GH-treated children and adolescents: analysis from the GeNeSIS observational research program. J Clin Endocrinol Metab. 2011 Jun;96(6):E1025-34. doi: 10.1210/jc.2010-3023. Epub 2011 Apr 13.