Predictive Value of the Insulin-like Growth Factor-1 (IGF-1) Generation Test for the Growth Response to Growth Hormone Treatment (PRED-IGF)

Predictive Value of Baseline and Stimulated Serum IGF-1 and IGFBP-3 During a Dose-escalation IGF-1 Generation Test for the 1 Year Growth Response to Growth Hormone (GH) Therapy in Short Children With Low IGF-1 and a Normal GH Peak in a Provocation Test

The evaluation of a standardized diagnostic test to predict the growth response in a 1 year trial with Growth Hormone (GH) treatment (carried out in the context of regular patient care) in non GH deficient short children with low serum insulin-like growth factor-1 (IGF-1).

Study Overview

• Status: Withdrawn
• Conditions: Idiopathic Short Stature
• Intervention / Treatment: Drug: Nutropin [Somatropin (rDNA origin) for injection]

• Study Type: Interventional
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 10 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 2.0 - 9.0 years for females, 2.0 - 10.0 yrs for males.
• Prepubertal stage (Tanner 1 for breast (B1) in females, or Tanner 1 for genitals (G1) for males).
• Bone age < 10 'years' (males) or < 9 'years' (females) according to Greulich and Pyle. The bone age will be read by the pediatric endocrinologist responsible for the pre-study screening visit.
• Height SDS < -2.5 for ethnically adequate references. For children of Dutch or Western European origin the 1997 nation-wide references for Dutch children will be used. For children of Moroccan or Turkish origin, the respective reference charts will be used. For children of other ethnicities, the 1977 North American (NCHS/WHO) reference will be used, as these charts have been accepted by WHO as world-wide standard from the age of 5 years.

Exclusion Criteria:

• Has a history of hypersensitivity to growth hormone or phenol (conservative added to GH in NutropinAq), or drugs with a similar chemical structure.
• Has abnormal baseline findings, any other medical condition(s) or laboratory findings that, in the opinion of the Investigator, might jeopardise the subject's safety or decrease the chance of obtaining satisfactory data needed to achieve the objective(s) of the study.
• Has a birth weight and/or length below -2 SDS for Swedish reference charts. Patients will not be excluded due to an unknown birth weight or length.
• Has a known cause of short stature, or any significant concomitant disease that is likely to interfere with growth or with the study schedule/objectives, or is a known contraindication to GH treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: NutropinAq

Drug: Nutropin [Somatropin (rDNA origin) for injection]; Doses in the diagnostic protocol are 0.7 and 1.4 mg/m2/day, injected by subcutaneous injection at bedtime for 2 weeks, divided by washout periods of preferably 4 weeks (accepted range 4-6 weeks). An additional period of 2 weeks on 2.8 mg/m2/day (after a washout period of 4-6 weeks) will be added if the IGF-I response on either dosage is insufficient (serum IGF-I SDS <0).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Peak serum IGF-1 level with GH (1.4 mg/m2/day) change from baseline.	Week 2

Secondary Outcome Measures

Outcome Measure	Time Frame
Delta IGF-1 SDS on 0.7 & 1.4 mg GH/m2/day	Baseline, week 2
Delta insulin-like growth factor binding protein-3 (IGFBP-3) standard deviation score (SDS) on 0.7 & 1.4 mg GH/m2/day	Baseline, week 2
Delta of the ratio IGF-1:IGFBP-3 SDS on 0.7 mg & 1.4 mg GH/m2/day	Baseline, week 2
Delta of the ratio IGF-1:IGFBP-2 (insulin-like growth factor binding protein-2) SDS on 0.7 mg & 1.4 mg GH/m2/day	Baseline, week 2
Peak IGFBP-3 SDS on 0.7 mg & 1.4 mg GH/m2/day	Baseline, week 2
Peak of the ratio IGF-1:IGFBP-3 SDS on 0.7 mg & 1.4 mg GH/m2/day	Baseline, week 2
Peak of the ratio IGF-1:IGFBP-2 SDS on 0.7 mg & 1.4 mg GH/m2/day	Baseline, week 2

Collaborators and Investigators

• Sponsor: Ipsen
• Investigators: Study Director: Ipsen Medical Director, MD, Ipsen

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): May 1, 2013
• Primary Completion (ANTICIPATED): May 31, 2013
• Study Completion (ANTICIPATED): May 31, 2013

Study Registration Dates

• First Submitted: August 24, 2011
• First Submitted That Met QC Criteria: September 21, 2011
• First Posted (ESTIMATE): September 22, 2011

Study Record Updates

• Last Update Posted (ACTUAL): August 5, 2019
• Last Update Submitted That Met QC Criteria: August 2, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Genetic Diseases, Inborn; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Developmental; Dwarfism
• Other Study ID Numbers: A-95-58035-017; 2010-019980-13 (EUDRACT_NUMBER)