Ghrelin Resistance in Adolescents With Idiopathic Scoliosis

Study Overview
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Brief Summary
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Adolescent idiopathic Scoliosis (AIS) is the most common spine pathology. It is opposed to secondary scoliosis due to chronic diseases. Many hypotheses have been made to elucidate the origin of this illness. Recently, the melatonin pathway has been investigated as pinealectomy of the chicken creates a scoliosis that resembles AIS and melatonin supplementation reverses the process. In addition administration of melatonin to AIS patients improved the pathology. However this hypothesis has shown controversial results. Recent studies have demonstrated melatonin cellular resistance in osteoblastic cells from AIS patients. Melatonin acts through G protein coupled receptor (GPCR), mainly using the Gi pathway. In AIS osteoblasts, this pathway is blocked leading to a decrease in the inactivation of the adenylyl cyclase and therefore maintenance of high level of cyclic adenosine monophosphate (cAMP) concentrations in the cells. As modulation of cAMP is important for osteogenesis such resistance may be critical for the initiation or the development of AIS. Gi signalization is used by several other GPCR, thus, this hormonal resistance could logically be found in other hormonal or mediator pathways. A precedent study previously focused on ghrelin in AIS, and demonstrated that AIS patients possess elevated plasmatic values of ghrelin. This study also observed decreased response to ghrelin in AIS cultures osteoblasts.

Official Title
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Ghrelin Cellular Resistance Study in Adolescents With Idiopathic Scoliosis

Conditions
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Scoliosis

Intervention / Treatment
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* Biological: Osteoblast sample


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Group 1 : AIS : spine deformity with angle above 10°,without detected cause Informed consent obtained Group 2 : Secondary scoliosis due to chronic illness, neurologic or syndromic, eligible for spine surgery Spine surgery for reason other than scoliosis Informed consent obtained Exclusion Criteria: Not primary scoliosis No consent Legal obstacle

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 15 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: patients with AIS<br>Patients will have 'Osteoblast sample' | Biological: Osteoblast sample<br>* culture osteoblasts obtained from vertebrae fragments from 30 patients with AIS and from 10 control patients with secondary scoliosis<br>|
| Experimental: control patients<br> | Biological: Osteoblast sample<br>* culture osteoblasts obtained from vertebrae fragments from 30 patients with AIS and from 10 control patients with secondary scoliosis<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Testing ghrelin cellular resistance by intracellular cAMP dosage | Testing ghrelin cellular resistance in AIS by measuring the variation of the intracellular cAMP level in response to ghrelin in osteoblast cells in vitro of AIS patients versus controls | baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ghrelin level in serum | Measure the ghrelin level in the serum of AIS patients versus controls | baseline | 
| ghrelin levels in cellular supernatants | Measure the ghrelin levels in cellular supernatants of osteoblasts from AIS and controls patients in order to evaluate the ghrelin production of the cells. | baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adolescent idiopathic Scoliosis, Ghrelin