A Trial to Evaluate the Correlation Between Spontaneous Catch-up Growth, Clinical Response to Saizen (Recombinant Human Growth Hormone, r-hGH) and Gene Expression Profiling in Children Small for Gestational Age (SGA)

NCT ID: NCT01067352

Last Updated: 2013-12-27

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-02-29
• Study Completion Date: 2009-07-31

Brief Summary

This open, multicentric, randomized, controlled study is planned to evaluate the correlation between gene expression, spontaneous catch-up growth and therapeutic response to Saizen in SGA children.

Detailed Description

This open, multicentric, randomized, controlled study was planned to identify genes activated by hGH in SGA children responders to treatment (making it possible in the near future to better identify SGA children likely to benefit from hGH treatment). Furthermore, the study would hopefully allow to verify which genes were responsible of spontaneous catch-up growth in children with diagnosis of SGA at birth but above the third percentile for height at the age of 24 months, and if these genes were the same activated by hGH during the treatment in participants responders. Sixty children born at term (i.e. after the 37th completed week of gestation) and with a diagnosis of SGA (defined as a length less than tenth percentile according to the Italian reference table published by Bertini and Fabris) were planned to be enrolled in the study. Forty participants (group A) were still less than third percentile for height (according to the Tanner reference table) at the age of 24 months, the remaining 20 (group B) being more than or equal to third percentile (thus showing a spontaneous catch-up growth). Group A was randomized to receive Saizen at the daily dose of 0.067 mg/kg (Group A1) or no treatment (Group A2) for two years. All participants were to undergo full clinical examination and blood chemistry at baseline visit and visit after 1,6,12,18 and 24 months for a period of two years. Gene expression analysis using the Clontech Atlas Human Array was performed in all participants at baseline and after one year in order to identify the possible correlation between catch-up growth (either spontaneous or drug-induced) and expression of some genes.

OBJECTIVES

Primary objective:

• To evaluate the correlation between gene expression profiling and catch-up growth (either spontaneous or drug induced after one year of treatment) in SGA children.

Secondary Objectives:

• To evaluate the percentage of participants not treated who show a spontaneous catch-up growth during the two years of observation.
• To assess the safety and tolerability of early treatment with Saizen

Conditions

Infant, Small for Gestational Age

Keywords

Infant, small for gestational age; Growth hormone; Saizen

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Group A (A1)

Participants were allocated to Group A if were still third percentile for height (according to the Tanner reference table) at the age of 4-6 years. Group A would be then randomized to receive Saizen at the daily dose of 0.035 milligram (mg)/kilogram (kg) (Group A1) or no treatment (Group A2) for two years.

Group Type: EXPERIMENTAL

Recombinant human growth hormone (r-hGH)

Intervention Type: DRUG

Recombinant human GH were administered subcutaneously (s.c) at the daily dose of 0.067 mg/kg of body weight to Group A1.

Group A (A2)

Participants were allocated to Group A if were still third percentile for height (according to the Tanner reference table) at the age of 4-6 years. Group A would be then randomized to receive no treatment (Group A2) for two years.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Group B

Participants were allocated to Group B being third percentile (thus showing a spontaneous catch-up growth).

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Recombinant human growth hormone (r-hGH)

Recombinant human GH were administered subcutaneously (s.c) at the daily dose of 0.067 mg/kg of body weight to Group A1.

Intervention Type: DRUG

Other Intervention Names

Saizen

Eligibility Criteria

Inclusion Criteria

• SGA at birth (defined as a length at birth equal or below the tenth percentile according to the Italian reference table of Bertini and Fabris)
• Age of 24 Months
• Caucasic
• Born at term (i.e. after the 37th completed week of gestation)
• Height equal or below (Group A) or up (Group B) the third percentile at the age of 24 months according to the Tanner reference table
• Sufficient GH secretion (more than 10 nanogram (ng)/milliliter (ml)) at least to one of the tests commonly used at that age (glucagon, Levo-dopa, arginine, clonidine, Growth Hormone Releasing Hormone (GHRH), GH integrated secretion)
• Normal level of Thyroid-stimulating hormone (THS), Free Triiodothyronine (FT3), Free Thyroxine (FT4), Insulin-like growth factor 1(IGF-1), insulin and haemoglobin A1c (HbA1c)
• Normal level of Immunoglobulin A (IgA)
• Children parents willing to comply with the protocol for the whole duration of the study
• A written Informed Consent before the baseline visit must be obtained from the parent(s) / legal guardian(s)

Exclusion Criteria

• Congenital malformations (including Silver-Russel syndrome)
• Known abnormal karyotype, especially in girls
• Twins
• Severe psychomotor retardation
• Previous or ongoing treatment with anabolic steroids or r-hGH
• Treatments interfering with the immune system (including bacterial lysate)
• Severe chronic illnesses
• Autoimmune diseases

• Minimum Eligible Age: 4 Years
• Maximum Eligible Age: 6 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Serono S.P.A., Italy

INDUSTRY

Sponsor Role: collaborator

Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Responsible

Role: STUDY_DIRECTOR

Merck Serono S.P.A., Italy

Locations

Merck Serono S.p.A.

Roma, , Italy

Countries

Italy

Other Identifiers

IMP23681

Identifier Type: -

Identifier Source: org_study_id