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

Primary Purpose

Anorexia Nervosa, Interruption of Growth, Delayed Puberty

Status

Completed

Phase

Phase 2

Locations

France

Study Type

Interventional

Intervention

SOMATROPINE* : Norditropine® simplexx®

Placebo

About this trial

This is an interventional treatment trial for Anorexia Nervosa focused on measuring anorexia nervosa, GH, Growth velocity

Eligibility Criteria

8 Years - 203 Months (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Robert Debré Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

SOMATROPINE* : Norditropine® simplexx®

Placebo

Arm Description

SOMATROPINE* : Norditropine® simplexx®

Placebo

Outcomes

Primary Outcome Measures

the growth-velocity

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

growth-velocity

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.

Body composition

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.

Psychological changes

Psychological changes that will be assessed between the 2 arms at the end of the two years of clinical trial.

Full Information

NCT ID

NCT01626833

First Posted

June 21, 2012

Last Updated

June 7, 2021

Sponsor

Assistance Publique - Hôpitaux de Paris

Collaborators

Novo Nordisk A/S

1. Study Identification

Unique Protocol Identification Number

NCT01626833

Brief Title

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

Acronym

OREX

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2021

Overall Recruitment Status

Completed

Study Start Date

March 2013 (Actual)

Primary Completion Date

March 2021 (Actual)

Study Completion Date

March 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Assistance Publique - Hôpitaux de Paris

Collaborators

Novo Nordisk A/S

4. Oversight

Data Monitoring Committee

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Anorexia Nervosa, Interruption of Growth, Delayed Puberty, Osteopenia With Failure of Acquisition of Bone Mass

Keywords

anorexia nervosa, GH, Growth velocity

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

15 (Actual)

8. Arms, Groups, and Interventions

Arm Title

SOMATROPINE* : Norditropine® simplexx®

Arm Type

Active Comparator

Arm Description

SOMATROPINE* : Norditropine® simplexx®

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo

Intervention Type

Drug

Intervention Name(s)

SOMATROPINE* : Norditropine® simplexx®

Other Intervention Name(s)

SOMATROPINE

Intervention Description

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.

Intervention Type

Biological

Intervention Name(s)

Placebo

Intervention Description

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.

Primary Outcome Measure Information:

Title

the growth-velocity

Description

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

Time Frame

1 year

Secondary Outcome Measure Information:

Title

growth-velocity

Description

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.

Time Frame

2 years

Title

Body composition

Description

Time Frame

2 years

Title

Psychological changes

Description

Psychological changes that will be assessed between the 2 arms at the end of the two years of clinical trial.

Time Frame

2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

8 Years

Maximum Age & Unit of Time

203 Months

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Leger Juliane, PhD

Organizational Affiliation

Assistance Publique - Hôpitaux de Paris

Official's Role

Principal Investigator

Facility Information:

Facility Name

Robert Debré Hospital

City

Paris

ZIP/Postal Code

75019

Country

France

12. IPD Sharing Statement

Citations:

PubMed Identifier

33772303

Citation

Leger J, Fjellestad-Paulsen A, Bargiacchi A, Pages J, Chevenne D, Alison M, Alberti C, Guilmin-Crepon S. One Year of GH Treatment for Growth Failure in Children With Anorexia Nervosa: A Randomized Placebo-Controlled Trial. J Clin Endocrinol Metab. 2021 Jun 16;106(7):e2535-e2546. doi: 10.1210/clinem/dgab203.

Results Reference

derived

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

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