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Is There a Sensibility Increased in the Growth Hormone at Child With Prader-Willi Syndrome?

Primary Purpose

Prader-Willi Syndrome, Growth Hormone Deficiency

Status
Completed
Phase
Phase 4
Locations
France
Study Type
Interventional
Intervention
Growth hormone (Genotonorm® or Omnitrope®)
DEXA, blood tests, H.G.P.O, osseous age.
biopsy
Sponsored by
University Hospital, Toulouse
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Prader-Willi Syndrome focused on measuring Prader-Willi Syndrome, Growth Hormone Deficiency

Eligibility Criteria

1 Year - 5 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. SPW and SPW-B :

    • Female or male child of age > or = 1 year
    • Child naïve of treatment by GH and that must begin a treatment with GH
    • Child covered by a national insurance scheme or an equivalent
    • Signature of the informed consent by one of both holders of the parental authority
  2. GHD :

    • Female or male child of age > or = 1 year
    • Child paired for the age (+/-on 1 year) and for the sex with regard to the group SWP
    • Child presenting a GH* deficiency defined by :

    Growth criteria of size (size) < 2 DS) Criteria of speed of growth (speed of growth < 1 DS over the last year) 2 tests of pharmacological stimulation of GH with peak GH max < 20 mUI

    • Child naïve of treatment by GH and that must begin a treatment with GH
    • Child covered by a national insurance scheme or an equivalent
    • Signature of the informed consent by one of both holders of the parental authority * The deficit in GH can be isolated or associated with one or several other hormonal deficits: deficit in TSH, deficit in ACTH, deficit in LH-FSH, deficit in prolactin. The child GHD can thus receive other treatments associated with the growth hormone.
  3. T : controls

    • Female or male child of age > or = 1 year
    • Child paired for the age (+/-on 1 year) and for the sex with regard to the group SWP
    • Child hospitalized at the hospital of the children of the University Hospital of Toulouse for a programmed surgical operation
    • Child covered by a national insurance scheme or an equivalent
    • Signature of the informed consent by one of both holders of the parental authority
  4. SPW-GH-B :

    • Female or male child of age > or = 1 year
    • Child hospitalized for a programmed surgical operation
    • Child covered by a national insurance scheme or an equivalent
    • Child treated with GH for at least 3 month
    • Signature of the informed consent by one of both holders of the parental authority

Exclusion Criteria:

  1. SPW and GHD

    • Child presenting a contraindication to the taking of growth hormone :
    • Growth cartilage welded
    • Tumoral pathology in process of evolution
    • Corticosteroid therapy (not substitute)
    • Allergy known about solvent
    • Badly balanced diabetes
    • Child presenting a hypersensitivity to the active principle or to one of the excipients of Genotonorm ® or Omnitrope ®
    • Child presenting a severe obesity (defined by a report weight / size > 200 %)
    • Child presenting clinical signs ENT (snores associated with a hypertrophy of the adenoids vegetations and\or the tonsils)
    • Child presenting clinical signs evoking a respiratory illness of the sleep (night-respiratory snores, respiratory breaks during the sleep)
  2. SPW-B:

    • Child presenting a hypersensitivity to the local anaesthetic with amide connecion
    • Child presenting a hypersensitivity to the components of the bandage Emlapatch®
    • Child presenting a hypersensitivity to one of the components of the lidocaïne aguettant without conservative®
    • Child presenting a porphyria
    • Child presenting a congenital methemoglobinemia
    • Child presenting a contraindication to Meopa : patients requiring a ventilation in pure oxygen, intracranial High blood pressure, Any change of the state of consciousness, preventing the cooperation of the patient, Pneumothorax, Bubbles of emphysema, Gaseous embolism, Accident of dive, abdominal gaseous Distension, Patient having received recently an ophthalmic gas (SF6, C3F8, C2F6) used in the eye surgery as long as persists a bubble of gas inside the eye and at least during a period of 3 months. Grave postoperative complications can arise in touch with the increase of the pressure intraocular, facial Traumatism interesting the region of application of the mask
  3. T : controls

    • Chronicle pathology in which an abnormality of growth would be involved
    • Other hormonal abnormalities
    • Children receiving a treatment on the long range, corticosteroid therapy in particular, being able to interfere with the sensibility to GH or to the insulin
    • Holder of the parental authority under supervision, guardianship or under protection of justice
    • Participation in another study simultaneously at this one

Sites / Locations

  • CHU Amiens Hôpital Nord Service Pédiatrie - Place Victor Pauchet
  • CHU Angers - 4 rue Larrey
  • CHG Avignon - 305, rue Raoul Follereau
  • CHU Besançon Hôpital Saint Jacques - 2 Place Saint Jacques
  • CHU Bordeaux Hôpital Pellegrin Service endocrinologie de l'enfant - Place Amélie Raba Léon
  • CHU Brest Département de Pédiatrie - 5, ave Foch
  • CHU Dijon Service de pédiatrie - 2, Bd Maréchal de lattre de Tassigny
  • CHU Grenoble Service de pédiatrie - BP 217
  • CHU La Rochelle Service de Pédiatrie - Rue du Dr Schweitzer
  • CHRU Lille Hôpital Jeanne de Flandre service de Pédiatrie
  • CHU Limoges Hôpital Mère Enfant Service Pédiatrie - 8, ave du Larrey
  • CHU Lorient Hôpital du Scorff Pôle Femme Mère Enfant - Rue Guiguen
  • CHU Lyon Hôpital Debrousse service Pédiatrie
  • AP-HM Hôptal La Timone Service de Pédiatrie Mutidisciplinaire
  • CHU Montpellier Hôpital Arnaud de Villeneuve - 371 ave du doyen Gaston Giraud
  • CHU Nantes Hôpital Mère Enfant Service de Pédiatrie
  • CHU Nice Hôpital Archet 2 - 151 route Saint Antoine de Ginestière
  • AP-HP Hôpital Necker Enfants Malades Service d'endocrinologie pédiatrique - 149 route de Sèvres
  • CHU Poitiers Service de Pédiatrie - Rue de la Miléterie
  • CHU Reims Service de Pédiatrie - 47, rue Cognacq-Jay
  • CHU Rouen Hôpital Nicolle - 1, rue de Germont
  • CHU Saint-Etienne Hôpital Nord Service de Pédiatrie
  • CHU Strasbourg Hôpital Haute-Pierre - Avenue Molière
  • CHU Toulouse Hôpital des Enfants Service d'endocrinologie - 330 ave de Grande Bretagne
  • CHRU Tours Centre de Pédiatrie Gatien de Clocheville
  • Hôpital d'Enfants - Rue Morvan

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

SPW

GHD

SPW-B

T

SPW-GH-B

Arm Description

Children presenting a Prader-Willi Syndrome

Patient deficient in Growth Hormone

Patient with Prader-Willi Syndrome who has Biopsy

Patient Control

Patient with Prader-Willi Syndrome taking growth Hormone and who has biopsy

Outcomes

Primary Outcome Measures

Measure of the circulating rates of IGF-I under treatment.
Measure of the circulating rates of IGF-I under treatment.
Measure of the circulating rates of IGF-I under treatment.
Measure of the circulating rates of IGF-I under treatment.
Measure of the circulating rates of IGF-I under treatment.

Secondary Outcome Measures

Measure of the circulating rate of IGFBP-3, GHBP, ghrelin and apelin.
Measure of physical composition's variation.
Measure of blood sugar level, H.G.P.O., and hyperglycaemia.
Measure of the sensibility at the growth hormone in vitro, on fibroblasts and adipocytes obtained by biopsy.
Measure of the circulating rate of IGFBP-3, GHBP, ghrelin and apelin.
Measure of the circulating rate of IGFBP-3, GHBP, ghrelin and apelin.
Measure of the circulating rate of IGFBP-3, GHBP, ghrelin and apelin.
Measure of physical composition's variation.
Measure of physical composition's variation.
Measure of physical composition's variation.
Measure of blood sugar level, H.G.P.O., and hyperglycaemia.
Measure of blood sugar level, H.G.P.O., and hyperglycaemia.
Measure of blood sugar level, H.G.P.O., and hyperglycaemia.
Measure of the sensibility at the growth hormone in vitro, on fibroblasts and adipocytes obtained by biopsy.
Measure of the sensibility at the growth hormone in vitro, on fibroblasts and adipocytes obtained by biopsy.
Measure of the sensibility at the growth hormone in vitro, on fibroblasts and adipocytes obtained by biopsy.

Full Information

First Posted
November 6, 2009
Last Updated
September 17, 2021
Sponsor
University Hospital, Toulouse
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1. Study Identification

Unique Protocol Identification Number
NCT01298180
Brief Title
Is There a Sensibility Increased in the Growth Hormone at Child With Prader-Willi Syndrome?
Official Title
Is There a Sensibility Increased in the Growth Hormone at Child With Prader-Willi Syndrome?
Study Type
Interventional

2. Study Status

Record Verification Date
September 2021
Overall Recruitment Status
Completed
Study Start Date
January 2009 (undefined)
Primary Completion Date
May 2013 (Actual)
Study Completion Date
May 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Toulouse

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to estimate the sensibility at the growth hormone in vivo at the children presenting a Prader-Willi syndrome (SPW) in comparison with children presenting a deficit in growth hormone (GHD).
Detailed Description
Estimate the sensibility at the growth hormone in vivo at the children presenting a Prader-Willi syndrome (SPW) in comparison with children presenting a deficit in growth hormone (GHD) by the measure of the circulating rates of IGF-I under treatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prader-Willi Syndrome, Growth Hormone Deficiency
Keywords
Prader-Willi Syndrome, Growth Hormone Deficiency

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
111 (Actual)

8. Arms, Groups, and Interventions

Arm Title
SPW
Arm Type
Experimental
Arm Description
Children presenting a Prader-Willi Syndrome
Arm Title
GHD
Arm Type
Experimental
Arm Description
Patient deficient in Growth Hormone
Arm Title
SPW-B
Arm Type
Experimental
Arm Description
Patient with Prader-Willi Syndrome who has Biopsy
Arm Title
T
Arm Type
Experimental
Arm Description
Patient Control
Arm Title
SPW-GH-B
Arm Type
Experimental
Arm Description
Patient with Prader-Willi Syndrome taking growth Hormone and who has biopsy
Intervention Type
Drug
Intervention Name(s)
Growth hormone (Genotonorm® or Omnitrope®)
Intervention Description
drug : the treatment will be begun in progressive dose by beginning by ¼ of the dose the first week, then ½ of the dose the second week, then 3/4 of the dose the third week and total dose the fourth week.
Intervention Type
Procedure
Intervention Name(s)
DEXA, blood tests, H.G.P.O, osseous age.
Intervention Description
SPW, GHD, SPW-B : blood tests : centralized dosage H.G.P.O : adjusted to children's age.
Intervention Type
Procedure
Intervention Name(s)
biopsy
Intervention Description
Biopsy : Cutaneous and fat tissue biopsy.
Primary Outcome Measure Information:
Title
Measure of the circulating rates of IGF-I under treatment.
Time Frame
Before starting treatment: baseline (J0)
Title
Measure of the circulating rates of IGF-I under treatment.
Time Frame
1 month (M1)
Title
Measure of the circulating rates of IGF-I under treatment.
Time Frame
3 month (M3)
Title
Measure of the circulating rates of IGF-I under treatment.
Time Frame
6 month (M6)
Title
Measure of the circulating rates of IGF-I under treatment.
Time Frame
1 year (M12)
Secondary Outcome Measure Information:
Title
Measure of the circulating rate of IGFBP-3, GHBP, ghrelin and apelin.
Time Frame
Before starting treatment (J0)
Title
Measure of physical composition's variation.
Time Frame
Before starting treatment (J0)
Title
Measure of blood sugar level, H.G.P.O., and hyperglycaemia.
Time Frame
Before starting treatment (J0)
Title
Measure of the sensibility at the growth hormone in vitro, on fibroblasts and adipocytes obtained by biopsy.
Time Frame
Before starting treatment (J0)
Title
Measure of the circulating rate of IGFBP-3, GHBP, ghrelin and apelin.
Time Frame
3 months (M3)
Title
Measure of the circulating rate of IGFBP-3, GHBP, ghrelin and apelin.
Time Frame
6 months (M6)
Title
Measure of the circulating rate of IGFBP-3, GHBP, ghrelin and apelin.
Time Frame
1 year (M12)
Title
Measure of physical composition's variation.
Time Frame
3 months (M3)
Title
Measure of physical composition's variation.
Time Frame
6 months (M6)
Title
Measure of physical composition's variation.
Time Frame
1 year (M12)
Title
Measure of blood sugar level, H.G.P.O., and hyperglycaemia.
Time Frame
3 months (M3)
Title
Measure of blood sugar level, H.G.P.O., and hyperglycaemia.
Time Frame
6 months (M6)
Title
Measure of blood sugar level, H.G.P.O., and hyperglycaemia.
Time Frame
1 year (M12)
Title
Measure of the sensibility at the growth hormone in vitro, on fibroblasts and adipocytes obtained by biopsy.
Time Frame
3 months (M3)
Title
Measure of the sensibility at the growth hormone in vitro, on fibroblasts and adipocytes obtained by biopsy.
Time Frame
6 months (M6)
Title
Measure of the sensibility at the growth hormone in vitro, on fibroblasts and adipocytes obtained by biopsy.
Time Frame
1 year (M12)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
5 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: SPW and SPW-B : Female or male child of age > or = 1 year Child naïve of treatment by GH and that must begin a treatment with GH Child covered by a national insurance scheme or an equivalent Signature of the informed consent by one of both holders of the parental authority GHD : Female or male child of age > or = 1 year Child paired for the age (+/-on 1 year) and for the sex with regard to the group SWP Child presenting a GH* deficiency defined by : Growth criteria of size (size) < 2 DS) Criteria of speed of growth (speed of growth < 1 DS over the last year) 2 tests of pharmacological stimulation of GH with peak GH max < 20 mUI Child naïve of treatment by GH and that must begin a treatment with GH Child covered by a national insurance scheme or an equivalent Signature of the informed consent by one of both holders of the parental authority * The deficit in GH can be isolated or associated with one or several other hormonal deficits: deficit in TSH, deficit in ACTH, deficit in LH-FSH, deficit in prolactin. The child GHD can thus receive other treatments associated with the growth hormone. T : controls Female or male child of age > or = 1 year Child paired for the age (+/-on 1 year) and for the sex with regard to the group SWP Child hospitalized at the hospital of the children of the University Hospital of Toulouse for a programmed surgical operation Child covered by a national insurance scheme or an equivalent Signature of the informed consent by one of both holders of the parental authority SPW-GH-B : Female or male child of age > or = 1 year Child hospitalized for a programmed surgical operation Child covered by a national insurance scheme or an equivalent Child treated with GH for at least 3 month Signature of the informed consent by one of both holders of the parental authority Exclusion Criteria: SPW and GHD Child presenting a contraindication to the taking of growth hormone : Growth cartilage welded Tumoral pathology in process of evolution Corticosteroid therapy (not substitute) Allergy known about solvent Badly balanced diabetes Child presenting a hypersensitivity to the active principle or to one of the excipients of Genotonorm ® or Omnitrope ® Child presenting a severe obesity (defined by a report weight / size > 200 %) Child presenting clinical signs ENT (snores associated with a hypertrophy of the adenoids vegetations and\or the tonsils) Child presenting clinical signs evoking a respiratory illness of the sleep (night-respiratory snores, respiratory breaks during the sleep) SPW-B: Child presenting a hypersensitivity to the local anaesthetic with amide connecion Child presenting a hypersensitivity to the components of the bandage Emlapatch® Child presenting a hypersensitivity to one of the components of the lidocaïne aguettant without conservative® Child presenting a porphyria Child presenting a congenital methemoglobinemia Child presenting a contraindication to Meopa : patients requiring a ventilation in pure oxygen, intracranial High blood pressure, Any change of the state of consciousness, preventing the cooperation of the patient, Pneumothorax, Bubbles of emphysema, Gaseous embolism, Accident of dive, abdominal gaseous Distension, Patient having received recently an ophthalmic gas (SF6, C3F8, C2F6) used in the eye surgery as long as persists a bubble of gas inside the eye and at least during a period of 3 months. Grave postoperative complications can arise in touch with the increase of the pressure intraocular, facial Traumatism interesting the region of application of the mask T : controls Chronicle pathology in which an abnormality of growth would be involved Other hormonal abnormalities Children receiving a treatment on the long range, corticosteroid therapy in particular, being able to interfere with the sensibility to GH or to the insulin Holder of the parental authority under supervision, guardianship or under protection of justice Participation in another study simultaneously at this one
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Maithé TAUBER, MD
Organizational Affiliation
University Hospital, Toulouse
Official's Role
Principal Investigator
Facility Information:
Facility Name
CHU Amiens Hôpital Nord Service Pédiatrie - Place Victor Pauchet
City
Amiens
ZIP/Postal Code
80054
Country
France
Facility Name
CHU Angers - 4 rue Larrey
City
Angers
ZIP/Postal Code
49000
Country
France
Facility Name
CHG Avignon - 305, rue Raoul Follereau
City
Avignon
ZIP/Postal Code
84902
Country
France
Facility Name
CHU Besançon Hôpital Saint Jacques - 2 Place Saint Jacques
City
Besancon
ZIP/Postal Code
25000
Country
France
Facility Name
CHU Bordeaux Hôpital Pellegrin Service endocrinologie de l'enfant - Place Amélie Raba Léon
City
Bordeaux
ZIP/Postal Code
33076
Country
France
Facility Name
CHU Brest Département de Pédiatrie - 5, ave Foch
City
Brest
ZIP/Postal Code
29609
Country
France
Facility Name
CHU Dijon Service de pédiatrie - 2, Bd Maréchal de lattre de Tassigny
City
Dijon
ZIP/Postal Code
21000
Country
France
Facility Name
CHU Grenoble Service de pédiatrie - BP 217
City
Grenoble
ZIP/Postal Code
38043
Country
France
Facility Name
CHU La Rochelle Service de Pédiatrie - Rue du Dr Schweitzer
City
La Rochelle
ZIP/Postal Code
17000
Country
France
Facility Name
CHRU Lille Hôpital Jeanne de Flandre service de Pédiatrie
City
Lille
ZIP/Postal Code
59037
Country
France
Facility Name
CHU Limoges Hôpital Mère Enfant Service Pédiatrie - 8, ave du Larrey
City
Limoges
ZIP/Postal Code
87042
Country
France
Facility Name
CHU Lorient Hôpital du Scorff Pôle Femme Mère Enfant - Rue Guiguen
City
Lorient
ZIP/Postal Code
56100
Country
France
Facility Name
CHU Lyon Hôpital Debrousse service Pédiatrie
City
Lyon
ZIP/Postal Code
69322
Country
France
Facility Name
AP-HM Hôptal La Timone Service de Pédiatrie Mutidisciplinaire
City
Marseille
ZIP/Postal Code
13385
Country
France
Facility Name
CHU Montpellier Hôpital Arnaud de Villeneuve - 371 ave du doyen Gaston Giraud
City
Montpellier
ZIP/Postal Code
34000
Country
France
Facility Name
CHU Nantes Hôpital Mère Enfant Service de Pédiatrie
City
Nantes
ZIP/Postal Code
44093
Country
France
Facility Name
CHU Nice Hôpital Archet 2 - 151 route Saint Antoine de Ginestière
City
Nice
ZIP/Postal Code
06202
Country
France
Facility Name
AP-HP Hôpital Necker Enfants Malades Service d'endocrinologie pédiatrique - 149 route de Sèvres
City
Paris
ZIP/Postal Code
75015
Country
France
Facility Name
CHU Poitiers Service de Pédiatrie - Rue de la Miléterie
City
Poitiers
ZIP/Postal Code
86021
Country
France
Facility Name
CHU Reims Service de Pédiatrie - 47, rue Cognacq-Jay
City
Reims
ZIP/Postal Code
51092
Country
France
Facility Name
CHU Rouen Hôpital Nicolle - 1, rue de Germont
City
Rouen
ZIP/Postal Code
76000
Country
France
Facility Name
CHU Saint-Etienne Hôpital Nord Service de Pédiatrie
City
Saint-etienne
ZIP/Postal Code
42055
Country
France
Facility Name
CHU Strasbourg Hôpital Haute-Pierre - Avenue Molière
City
Strasbourg
ZIP/Postal Code
67200
Country
France
Facility Name
CHU Toulouse Hôpital des Enfants Service d'endocrinologie - 330 ave de Grande Bretagne
City
Toulouse
ZIP/Postal Code
31059
Country
France
Facility Name
CHRU Tours Centre de Pédiatrie Gatien de Clocheville
City
Tours
ZIP/Postal Code
37044
Country
France
Facility Name
Hôpital d'Enfants - Rue Morvan
City
Vandoeuvre Les Nancy
ZIP/Postal Code
54511
Country
France

12. IPD Sharing Statement

Citations:
PubMed Identifier
24406482
Citation
Cadoudal T, Buleon M, Sengenes C, Diene G, Desneulin F, Molinas C, Eddiry S, Conte-Auriol F, Daviaud D, Martin PG, Bouloumie A, Salles JP, Tauber M, Valet P. Impairment of adipose tissue in Prader-Willi syndrome rescued by growth hormone treatment. Int J Obes (Lond). 2014 Sep;38(9):1234-40. doi: 10.1038/ijo.2014.3. Epub 2014 Jan 10.
Results Reference
result
PubMed Identifier
34040195
Citation
Eddiry S, Diene G, Molinas C, Salles J, Auriol FC, Gennero I, Bieth E, Skryabin BV, Rozhdestvensky TS, Burnett LC, Leibel RL, Tauber M, Salles JP. SNORD116 and growth hormone therapy impact IGFBP7 in Prader-Willi syndrome. Genet Med. 2021 Sep;23(9):1664-1672. doi: 10.1038/s41436-021-01185-y. Epub 2021 May 26.
Results Reference
result
PubMed Identifier
24916642
Citation
Bieth E, Eddiry S, Gaston V, Lorenzini F, Buffet A, Conte Auriol F, Molinas C, Cailley D, Rooryck C, Arveiler B, Cavaille J, Salles JP, Tauber M. Highly restricted deletion of the SNORD116 region is implicated in Prader-Willi Syndrome. Eur J Hum Genet. 2015 Feb;23(2):252-5. doi: 10.1038/ejhg.2014.103. Epub 2014 Jun 11.
Results Reference
result

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Is There a Sensibility Increased in the Growth Hormone at Child With Prader-Willi Syndrome?

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