Clinical trial NCT00256126: Predictive Markers in Growth Hormone Deficiency (GHD) and Turner Syndrome (TS) Children Treated With SAIZEN®
Official title: A Phase IV Open-label Study of Predictive Markers in Growth Hormone Deficient and Turner Syndrome Pre-pubertal Children Treated With SAIZEN®
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Growth Hormone Deficiency
Turner Syndrome
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2005-11-21
Enrollment: 318
Sex: ALL
Minimum age (years): 2
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study aims at identifying the predictive markers after one month of Saizen therapy in Growth Hormone Deficiency (GHD) and Turner Syndrome children.


Eligibility criteria: Inclusion Criteria:

* One of the following diagnoses and candidacy for SAIZEN® therapy:

A) GHD: documented pre-established diagnosis of GHD with a growth hormone (GH) peak response of \<10 microgram per liter (mcg/L) with 2 GH stimulation tests, without priming with oestradiol.

B) Turner syndrome: documented pre-established diagnosis by karyotype.

* Prepubertal status according to Tanner Pre-established history of normal thyroid function or adequate substitution for at least 3 months.
* Weight for stature within the population specific normal range (\>5th and \<95th percentiles) for gender Willingness and ability to comply with the protocol for the duration of the study.
* Parent's or guardian's written informed consent, given before any study related procedure that is not part of the subject's normal medical care, with the understanding that the subject or parent/guardian may withdraw consent at any time without prejudice to future medical care. If the child is old enough to read and write, a separate assent form will be given.

Exclusion Criteria:

* Acquired GHD due to central nervous system tumour, trauma, infection, infiltration (documented by imaging), and history of irradiation or cranial surgery
* Previous treatment with GH, growth hormone-releasing hormone (GHRH), anabolic steroids or any treatment affecting growth.
* Previous treatment with corticosteroids, except in case of topical or inhaled corticosteroid administration for atopic disease. Corticosteroids for hormonal substitution are also allowed if the condition and the treatment regimen have been stable for at least 3 months.
* Severe associated pathology affecting growth such as malnutrition, malabsorption, or bone dysplasia.
* Chronic severe kidney disease.
* Chronic severe liver disease.
* Chronic infectious disease.
* Acute or severe illness during the previous 6 months.
* Significant concomitant illness that would interfere with participation or assessment in this study.
* Active malignancy (except non-melanomatous skin malignancies that have undergone surgical excision and/or biopsy, diagnosis and treatment to resolution)
* History or active Idiopathic intra-cranial hypertension (benign intracranial hypertension or pseudo-tumor cerebri).
* Diabetes Mellitus type I \& II.
* Any autoimmune disease.
* Previous screening failure in this study.
* Use of an investigational drug or participation in another clinical study within the last three months.

Primary outcomes:
measure: Change From Baseline in Insulin Like Growth Factor-1 Standard Deviation Score (IGF-1 SDS) at Month 1
timeFrame: Baseline, Month 1
Secondary outcomes:
measure: Change From Baseline in Insulin-like Growth Factor Binding Protein - 3 (IGFBP-3) Level at Month 1
timeFrame: Baseline, Month 1
measure: Change From Baseline in Fasting Glucose Levels at Month 1
timeFrame: Baseline, Month 1
measure: Change From Baseline in Fasting Insulin Levels at Month 1
timeFrame: Baseline, Month 1
measure: Change From Baseline in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) at Month 1
timeFrame: Baseline, Month 1
measure: Change From Baseline in Bone Alkaline Phosphatase Levels at Month 1
timeFrame: Baseline, Month 1
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
facility: Local Medical Information Office
city: Sydney
country: Australia
facility: Local Medical Information Office
city: Vienna
country: Austria
facility: Local Medical Information Office
city: Mississauga
country: Canada
facility: Local Medical Information Office
city: Paris
country: France
facility: Local Medical InformationOffice
city: Munich
country: Germany
facility: Local Medical Information Office
city: Rome
country: Italy
facility: Local Medical Information Office
city: Oslo
country: Norway
facility: Local Medical Information Office
city: Russia
country: Russian Federation
facility: Local Medical Information Office
city: Singapore
country: Singapore
facility: Local Medical Information Office
city: Madrid
country: Spain
facility: Local Medical Information Office
city: Stockholm
country: Sweden
facility: Local Medical Information Office
city: Feltham
country: United Kingdom
facility: Local Medical Information Office
Study officials:
affiliation: Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References:
citation: Stevens A, Clayton P, Tato L, Yoo HW, Rodriguez-Arnao MD, Skorodok J, Ambler GR, Zignani M, Zieschang J, Della Corte G, Destenaves B, Champigneulle A, Raelson J, Chatelain P. Pharmacogenomics of insulin-like growth factor-I generation during GH treatment in children with GH deficiency or Turner syndrome. Pharmacogenomics J. 2014 Feb;14(1):54-62. doi: 10.1038/tpj.2013.14. Epub 2013 Apr 9.
citation: Stevens A, Murray P, De Leonibus C, Garner T, Koledova E, Ambler G, Kapelari K, Binder G, Maghnie M, Zucchini S, Bashnina E, Skorodok J, Yeste D, Belgorosky A, Siguero JL, Coutant R, Vangsoy-Hansen E, Hagenas L, Dahlgren J, Deal C, Chatelain P, Clayton P. Gene expression signatures predict response to therapy with growth hormone. Pharmacogenomics J. 2021 Oct;21(5):594-607. doi: 10.1038/s41397-021-00237-5. Epub 2021 May 27.
citation: Murray PG, Stevens A, De Leonibus C, Koledova E, Chatelain P, Clayton PE. Transcriptomics and machine learning predict diagnosis and severity of growth hormone deficiency. JCI Insight. 2018 Apr 5;3(7):e93247. doi: 10.1172/jci.insight.93247. eCollection 2018 Apr 5.
citation: Valsesia A, Chatelain P, Stevens A, Peterkova VA, Belgorosky A, Maghnie M, Antoniazzi F, Koledova E, Wojcik J, Farmer P, Destenaves B, Clayton P; PREDICT Investigator group. GH deficiency status combined with GH receptor polymorphism affects response to GH in children. Eur J Endocrinol. 2015 Dec;173(6):777-89. doi: 10.1530/EJE-15-0474. Epub 2015 Sep 4.