Severe Decrease of Growth Velocity in Children With Anorexia Nervosa.Therapeutic Trial of Growth Hormone (OREX)

Study Description

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Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Anorexia Nervosa; Interruption of Growth; Delayed Puberty; Osteopenia With Failure of Acquisition of Bone Mass	Drug: SOMATROPINE* : Norditropine® simplexx®; Biological: Placebo	Phase 2; Phase 3

Detailed Description:

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	15 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Triple (Participant, Care Provider, Investigator)
Primary Purpose:	Treatment
Official Title:	Severe Decrease of Growth Velocity in Children With Anorexia Nervosa. Therapeutic Trial of Growth Hormone
Study Start Date :	March 2013
Estimated Primary Completion Date :	March 2022
Estimated Study Completion Date :	March 2022

Arms and Interventions

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
Active Comparator: SOMATROPINE* : Norditropine® simplexx®; SOMATROPINE* : Norditropine® simplexx®	Drug: SOMATROPINE* : Norditropine® simplexx®; SOMATROPINE* : Norditropine® simplexx® - 15 mg/1,5 ml, injectable solution:Treatment with hGH is administered at a dose of 0.05 mg / kg / day (0.35 mg / kg / week) subcutaneously daily, preferably in the evening. The dose of hGH treatment will be adjusted according to weight gain, and reduced by 10% if the serum values of IGF-I SDS above 2.5 on 2 consecutive determinations at 3-month intervals are discovered by the biologist.; Other Name: SOMATROPINE
Placebo Comparator: Placebo; Placebo	Biological: Placebo; Treatment with placebo is administered at a dose of 0.05 mg / kg / day (0.35 mg / kg / week) subcutaneously daily, preferably in the evening. The dose of placebo will be adjusted according to weight gain, and reduced by 10% if the serum values of IGF-I SDS above 2.5 on 2 consecutive determinations at 3-month intervals are discovered by the biologist.

Outcome Measures

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Primary Outcome Measures :

1. the growth-velocity [ Time Frame: 1 year ]
   the growth velocity will be evaluated 1 year after the start of the trial (cm/1an) compared between the group with the placebo and hGH

Secondary Outcome Measures :

1. growth-velocity [ Time Frame: 2 years ]
   The secondary endpoints will be the growth-velocity expressed in SDS that will be assessed between the 2 arms at the end of the two years of clinical trial.
2. Body composition [ Time Frame: 2 years ]
   The data of body composition that will be assessed between the 2 arms at the end of the two years of 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.
3. Psychological changes [ Time Frame: 2 years ]
   Psychological changes that will be assessed between the 2 arms at the end of the two years of clinical trial.

Eligibility Criteria

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Ages Eligible for Study:	8 Years to 203 Months (Child)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

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Locations

France
Robert Debré Hospital
Paris, France, 75019

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

Novo Nordisk A/S

Investigators

Principal Investigator:	Leger Juliane, PhD	Assistance Publique - Hôpitaux de Paris

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:	NCT01626833 History of Changes
Other Study ID Numbers:	P090903; 2010-018560-16 ( EudraCT Number )
First Posted:	June 25, 2012
Last Update Posted:	March 2, 2018
Last Verified:	February 2018

Keywords provided by Assistance Publique - Hôpitaux de Paris:

anorexia nervosa; GH; Growth velocity

Additional relevant MeSH terms:

Anorexia; Anorexia Nervosa; Bone Diseases, Metabolic; Puberty, Delayed; Signs and Symptoms, Digestive; Signs and Symptoms; Feeding and Eating Disorders; Mental Disorders	Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Gonadal Disorders; Endocrine System Diseases; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs