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Efficacy Study of Recombinant Growth Hormone on Muscle Function in Children Long-term Treated With Glucocorticoid

Phase 3
Completed
Conditions
Chronic Disease
Glucocorticoid Therapy, Response to
Growth Retardation
Interventions
Device: GH treatment
Registration Number
NCT00813189
Lead Sponsor
Association REMEDE
Brief Summary

Children suffering from chronic disease and receiving long-term glucocorticoid therapy suffer over years from severe growth retardation and profoundly altered body composition. They consist in a marked increase in fat mass and a decrease in lean body mass. Published studies have shown that Growth Hormone (GH) treatment in children with Juvenile Idiopathic Arthritis can improve body composition by increasing lean mass and by preventing increase in fat mass. The aim of the present protocol is to evaluate whether the increase in lean body mass observed during GH treatment is associated with changes in muscle strength and mass.

In order to be able to evaluate the effect of GH on the muscle a comparative group is needed. Therefore it will be proposed to delay in a group of patients the start of Growth Hormone(GH) treatment by 6 months. As most publications have shown a maximum effect of GH within the first year of treatment, six months should be enough to evaluate short-term effect of GH on the muscle. Therefore, this study will be a randomized trial: immediate start of Growth Hormone (GH) treatment versus start of Growth Hormone treatment 6 months later. After 6 months all children will be treated with GH. Therefore, the follow-up will be one year after baseline.

Detailed Description

The aim of the present protocol is to evaluate the effects of GH treatment in long-term steroid treated children, on muscle mass, and muscle strength. It will be an open, randomized, controlled, 2-parallel group study. The follow-up in this study will be one year. The objective of this study will be to evaluate short-term effects of GH treatment on muscle mass, muscle strength and body composition in children suffering from various diseases requiring steroid therapy. Expected pathologies are juvenile idiopathic arthritis, nephrotic syndrome, uveitis, systemic diseases and organ transplantation. Changes in muscle mass will be assessed by measuring the muscle and sub-cutaneous fat on the cross sectional area of the thigh by MRI. MRI offer the advantage of non-invasive technique, allowing serial and accurate measurements.Muscle strength will be performed by serial muscular testing of different muscular groups. Body composition will be assessed by DEXA. DEXA allows rapid, accurate and highly reproductible determination not only of bone mass but also of lean and fat mass of the whole body, with very low radiation exposure.It appears to be the most sensitive method for assessment of muscle wasting as well as of fat repartition that contribute to Cushing's appearance in steroid treated patients.

The present study will be performed in children with growth retardation related to long-term glucocorticoid treatment These patients had never been treated with GH. In order to be able to evaluate the effect of GH on the muscle a comparative group is needed. Therefore it will be proposed in the study to delay in a group of patient the start of GH treatment by 6 months. Six months should be enough to evaluate short-term effect of GH on the muscle and most publication have shown a maximum effect of GH within the first year of treatment. Therefore, this study will be a randomized trial: immediate start of GH treatment versus start of GH treatment 6 months later. After 6 months all children will be treated with GH. The dose administered in the present trial will be a GH dose already tested in glucocorticoid treated children (0.46 mg/kg/week)

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
30
Inclusion Criteria
  • Measured Height below -2 SD
  • Bone age below 13 years for a boy and below 11 years for a girl
  • Glucocorticosteroid treatment for 12 months at least
  • Glucocorticosteroid dose above or equal to 0.2 mg/kg/day of prednisone or equivalent dose over the last 12 months
  • Glucocorticosteroid treatment is anticipated to be sustained for 1 more year at least
  • The child benefits of the French social security cover
  • Child who has never been treated by GH.
  • Evidence of a personally signed and dated informed consent document indicating that the patient's parents/guardians and from the patient himself/herself if he/she is able to receive and understand the information have been informed of all pertinent aspects of the study.
  • No glucose intolerance or diabetes mellitus on an Oral Glucose Tolerance Test dated less than 3 months
Exclusion Criteria
  • Severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results and, in the judgment of the investigator, would make the subject inappropriate for entry into this trial.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
1 : early start (GH treatment) groupGH treatmentin the early start group, patients were treated with growth hormone for one year immediately after randomisation
Primary Outcome Measures
NameTimeMethod
The main criteria of efficacy will be - the mean strength changes assessed as a composite score (mean of the relative changes of the ten muscle functions tested): ∆ strength as % of baseline values :6 months-baseline.6 months
Secondary Outcome Measures
NameTimeMethod
Strength changes assessed as a composite score (mean of the relative changes of the ten muscle functions tested) as % of baseline values : 12 months-baseline and 12 months- 6 months, 18 months- 6 months for group B patients18 months

Trial Locations

Locations (1)

Hôpital Robert Debré

🇫🇷

Paris, France

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