E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Growth disorder in children born small for gestational age |
Vækstforstyrrelser hos børn med lav fødselsvægt |
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E.1.1.1 | Medical condition in easily understood language |
Growth disorder in children with low birth weight |
Vækstforstyrrelser hos børn med lav fødselsvægt |
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E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10040600 |
E.1.2 | Term | Short stature |
E.1.2 | System Organ Class | 100000004848 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the effects of insulin sensitization using Metformin on the circulating levels of IGF-1 over 6 months in SGA children started on GH treatment |
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E.2.2 | Secondary objectives of the trial |
1. To determine the effects of the intervention over 6 months on height velocity, insulin sensitivity, insulin secretion and glucose tolerance
2. To determine the effects of Metformin treatment on IGF-1 levels, height velocity, insulin sensitivity and body composition after 6 months of discontinuation of Metformin.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion Criteria:
• SGA children eligible for GH treatment according to EMA and NICE criteria
• Gestational age at birth >28 weeks
• Age 4-9 years in girls and 4-10 years in boys
• Prepubertal at start of treatment
• Naïve to GH therapy
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E.4 | Principal exclusion criteria |
Inclusion Criteria:
• SGA children eligible for GH treatment according to EMA and NICE criteria
• Gestational age at birth >28 weeks
• Age 4-9 years in girls and 4-10 years in boys
• Prepubertal at start of treatment
• Naïve to GH therapy
Exclusion Criteria
• Known or suspected allergy to GH
• Known or suspected hypersensitivity or allergy to Metformin
• Previous participation in a GH trial
• Severe learning difficulties
• Previous or active malignancy
• Benign intracranial hypertension
• Diabetes
• Growth failure due to chronic diseases, syndromes, or chromosomal anomalies
• Cardiac, pulmonary, hepatic or renal diseases associated with significant decompensation
• Psychological problems likely to lead to significant non-compliance
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E.5 End points |
E.5.1 | Primary end point(s) |
Circulating levels of IGF-I over 6 months in SGA children started on Metformin/placebo and Growth hormone |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After 6 and 12 months of growth hormone treatment |
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E.5.2 | Secondary end point(s) |
Effects of the intervention over 6 months on height velocity, insulin sensitivity, insulin secretion and glucose tolerance |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After 6 and 12 months of treatment |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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After 12 months of treatment |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |