Severe Decrease of Growth Velocity in Children With Anorexia Nervosa.Therapeutic Trial of Growth Hormone
Severe Decrease of Growth Velocity in Children With Anorexia Nervosa.Therapeutic Trial of Growth Hormone
Anorexia nervosa may be responsible for a catch- down or even an interruption of growth,
 delayed puberty and osteopenia with failure of acquisition of bone mass. The recovery of
 normal nutrition usually leads to a resumption of growth and pubertal development. However,
 despite a therapeutic nutritional and psychotherapeutic satisfactory approach, some patients
 have a significant short stature with reduced adult final height and a deficit of bone mass.
 The main objective is to evaluate the effect of growth hormone (hGH) treatment on the growth
 velocity in prepubertal children or children in early puberty with anorexia nervosa and
 significant reduction of height velocity. This is a single-center, controlled, randomized and
 double-blind clinical trial evaluating the efficacy of hGH treatment for 1 year against a
 placebo, on the growth velocity of prepubertal or children in early puberty with Anorexia
 nervosa and major catch-down.This period is followed by the evaluation of the hGH treatment
 in children receiving placebo and continued hGH treatment in the treatment arm for 1 year, in
 total 2 years of study for each child. This second period corresponds to an ethical
 consideration giving secondarily access to treatment for patients in the placebo group.
Patients will be evaluated at baseline and at 3, 6, 9, 12, 15, 18, 21 and 24 months after the
 start of the trial. This evaluation will include a clinical evaluation and a biological
 (IGF-I, IGFBP-3, leptin, ghrelin, adiponectin, mineral metabolism, thyroid function, 24 hours
 urinary cortisol, as well as conventional electrolyte tolerance parameters), psychological
 and nutritional study body composition by absorptiometry at 0, 12 and 24 months. Evaluations
 will be conducted at the Center for Clinical Investigation at Hospital Robert Debre. The
 primary endpoint will be the linear growth rate 1 year after the start of the trial expressed
 in cm/1 year in the group with hGH compared to the placebo group. The secondary endpoints
 will be the height velocity expressed in SDS (standard deviation score), the data of body
 composition and psychological changes that will be assessed between the 2 arms at the end of
 the two years of the clinical trial. The data of body composition obtained by dual photon
 absorptiometry and biological data of mineral metabolism and growth factors are expressed in
 Z score compared to normal references that we have established in France, in healthy subjects
 according to age, gender and pubertal stage.
Inclusion Criteria:

 -  Medical screening.

 -  Female and male subjects aged 8-16 years and 11 months, with clinical anorexia nervosa
 and / or reference to the diagnostic criteria of DSM-IV (1) before or at early puberty
 (Tanner stage 1 or 2) and with a prolonged Catch-Down for at least 18 months (HV ≤ 2
 cm / year), with bone age ≤ 12 years in girls and ≤14 years in boys.

 -  Anorexia nervosa diagnosed at least 1 year before the study

 -  Growth velocity documented for at least 18 months before inclusion

 -  As with any child with a severe Catch-Down an assessment of GH secretion must be
 performed before inclusion (in the context of care) in the trial, which is not
 conditioned by the GH peak value : GH value of <20 miu / L will lead to the production
 of a brain MRI (in the context of care) that have to be normal (normal
 hypothalamic-pituitary axis and absence of tumor pathology) to allow Inclusion of the
 patient.

 -  Normal glucose tolerance

 -  Stable metabolic state with of weight gain of at least 10% of body weight from the
 time the body mass index was the lowest in relation to the occurrence of the disease
 and normal blood electrolytes (no hypokalemia) .

 -  Subjects whose holders have signed parental consent

 -  Subjects whose holders of parental authority are affiliated to a social security
 scheme

 -  CMU (CMU universal medical coverage).

 Exclusion Criteria:

 -  Subjects in the mid-puberty (Tanner stage 3 or 4) or with menarche.

 -  Subjects with a chromosomal abnormality or other chronic disease associated chronic
 requiring long-term treatment.

 -  Impaired glucose tolerance or diabetes.

 -  Inability of the patient or the medical team to ensure the progress and monitoring
 under the protocol.

 -  Participation in another trial.

 -  Bradycardia ≤ 50 bpm.

 -  Children whose holders of parental authority are not beneficiaries of social security

 -  Contra-indication to SOMATROPINE