Growth Hormone Treatment for the Prevention of Short Stature in Young Girls With Turner Syndrome Before the Age of 4 Years

Collaborative Study to Assess the Effects of Treatment With Recombinant Growth Hormone Saizen® in the Prevention of Short Stature in Young Girls Suffering From Turner Syndrome Before the Age of 4 Years. Original French Title: Etude Collaborative Pour apprécier Les Effets du Traitement Par l'Hormone de Croissance Recombinante SAIZEN® Dans le Retard de Croissance de la Fillette Atteinte de Syndrome de Turner Avant l'âge de 4 Ans

The objective of this study is to evaluate the efficacy and safety of recombinant human growth hormone (r-hGH) treatment in girls with Turner Syndrome under the age of 4 years. After 4 years of treatment, height in these girls will be compared with an historical control group of untreated girls with Turner Syndrome, matched for age and height at baseline.

Study Overview

• Status: Completed
• Conditions: Turner's Syndrome
• Intervention / Treatment: Drug: r-hGH

• Study Type: Interventional
• Enrollment (Actual): 115
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Paris, France, 75935
    • Hôpital Robert Debré

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 4 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Young girls with turner syndrome proved by karyotype
• Growth hormone secretion confirmed with ornithin stimulation test
• Normal glucidic metabolism confirmed by assessment of HbA1c
• None associated severe pathology which could have impact on growth (i.e. renal insufficiency, decompensated heart failure)
• No previous or associated treatment with anabolic or sexual steroids
• Known parental height

Exclusion Criteria:

• Severe associated pathology with impact on growth
• Concomitant treatment with impact on growth
• Previous or associated treatment with anabolic steroids
• Associated growth hormone deficiency

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: r-hGH; Participants (girls) will receive r-hGH as a subcutaneous injection administered by a parent in the evening. During Years 1-2, the dose of r-hGH received will depend on participants' baseline height standard deviation score (SDS) relative to the general population standard: participants with a height SDS of -2 standard deviation (SD) or lower will receive 0.05 milligrams per kilogram (mg/kg) per day r-hGH and those with a height SDS between -1 and -2 SD will receive 0.035 mg/kg per day r-hGH. After 2 years of treatment, all participants will receive a fixed dose of 0.05 mg/kg per day for a further 2 years.	Drug: r-hGH; Subcutaneous administration.; Other Names: Saizen®
No Intervention: Historical Control; This arm will include matching (age and height) historical control participants (girls) with turner syndrome, who were born between 1961 and 1990 and were untreated.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Height SDS at Year 4	Height SDS was calculated as height minus reference mean height divided by standard deviation of the reference population. Height SDS reflects the height relative to a reference population of the same age and gender.	Year 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Abnormal Glycated Hemoglobin (HbA1c) Levels	HbA1c develops when hemoglobin, a protein within red blood cells that carries oxygen throughout the body, joins with glucose in the blood, becoming glycated. The higher the level of glucose in the blood, the higher the level of HbA1c is detectable on red blood cells. The normal range for HbA1c is 4 percent (%) to 5.9%. Number of participants, who had abnormal HbA1c levels any time during the assessment, were reported.	Baseline up to Year 2
Difference Between Bone Age (BA) and Chronological Age (CA) (BA-CA)	BA was determined using left wrist and hand X-ray. CA was determined using the date of birth. Difference of BA and CA (BA-CA) was reported.	Baseline, Year 1, Year 2
Number of Participants With Anti r-hGH Antibodies		Baseline up to Year 2
Number of Participants With Abnormal Insulin-Like Growth Factor 1 (IGF1) Levels	The normal range for IGF1 levels is 45 to 117 nanogram per milliliter (ng/mL) for girls aged less than (<) 3 years and 80 to 236 ng/mL for girls aged 3 to 6 years. Values outside the normal range were considered abnormal. Number of participants, who had abnormal IGF1 levels any time during the assessment, were reported.	Baseline up to Year 2
Number of Participants Who Reached Normal Height at Year 4	Participants with normal height were those who attained a height which was within +/- 2 height SDS of reference population standard. Height SDS was calculated as height minus reference mean height divided by standard deviation of the reference population. Height SDS reflects the height relative to a reference population of the same age and gender.	Year 4

Collaborators and Investigators

• Sponsor: Merck KGaA, Darmstadt, Germany

Publications and helpful links

General Publications

• Linglart A, Cabrol S, Berlier P, Stuckens C, Wagner K, de Kerdanet M, Limoni C, Carel JC, Chaussain JL; French Collaborative Young Turner Study Group. Growth hormone treatment before the age of 4 years prevents short stature in young girls with Turner syndrome. Eur J Endocrinol. 2011 Jun;164(6):891-7. doi: 10.1530/EJE-10-1048. Epub 2011 Mar 11.

Study record dates

Study Major Dates

• Study Start (Actual): February 29, 1992
• Primary Completion (Actual): March 31, 1999
• Study Completion (Actual): August 31, 2010

Study Registration Dates

• First Submitted: February 5, 2010
• First Submitted That Met QC Criteria: February 9, 2010
• First Posted (Estimate): February 10, 2010

Study Record Updates

• Last Update Posted (Actual): December 14, 2018
• Last Update Submitted That Met QC Criteria: June 12, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: Growth hormone; Turner syndrome; early treatment; r-hGH
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Endocrine System Diseases; Disease; Gonadal Disorders; Disorders of Sex Development; Urogenital Abnormalities; Congenital Abnormalities; Genetic Diseases, Inborn; Musculoskeletal Diseases; Bone Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Chromosome Disorders; Bone Diseases, Developmental; Sex Chromosome Disorders; Sex Chromosome Disorders of Sex Development; Syndrome; Turner Syndrome; Gonadal Dysgenesis; Dwarfism
• Other Study ID Numbers: GF 5834