Clinical trial NCT02829476: Ghrelin Resistance in Adolescents With Idiopathic Scoliosis
Official title: Ghrelin Cellular Resistance Study in Adolescents With Idiopathic Scoliosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Scoliosis
Keywords: Adolescent idiopathic Scoliosis
Ghrelin
Lead sponsor: University Hospital, Toulouse
Sponsor class: OTHER
First posted: 2016-07-12
Enrollment: 45
Sex: ALL
Minimum age (years): 12
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Testing ghrelin cellular resistance by intracellular cAMP dosage
timeFrame: baseline
Secondary outcomes:
measure: ghrelin level in serum
timeFrame: baseline
measure: ghrelin levels in cellular supernatants
timeFrame: baseline
Other outcomes:
Locations:
city: Toulouse
country: France
facility: University Hospital of Toulouse
Study officials:
affiliation: University Hospital, Toulouse
name: SALLES Jean-Pierre, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sales de Gauzy J, Gennero I, Delrous O, Salles JP, Lepage B, Accadbled F. Fasting total ghrelin levels are increased in patients with adolescent idiopathic scoliosis. Scoliosis. 2015 Nov 30;10:33. doi: 10.1186/s13013-015-0054-7. eCollection 2015.