Phosphoproteomic Profile of Children With Down Syndrome

Down Syndrome Clinical Trial

— PEPS  

Official title:

Exploratory Phosphoproteomic Study to Discover DYRK1A-Dependent Blood Biomarkers in TriSomy 21 Carriers

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06279208
• Other study ID #: 2023-A00272-43
• Status: Recruiting
• Start date: March 18, 2024
• Est. completion date: September 2024

Study information

• Verified date: March 2024
• Source: Perha Pharmaceuticals
• Contact: Emilie Chrétien
• Phone: 0222554572
• Email: chretien[@]perha-pharma.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

One of the major causes of cognitive disorders limiting the learning abilities of children with Down's syndrome is excess activity of the DYRK1A protein kinase, whose gene is located on chromosome 21. Consequently, variations in the level of phosphorylation, and hence activity, of DYRK1A target proteins involved in synaptic transmission, could identify mechanisms underlying these cognitive disorders. Several studies have shown that plasma proteins can reflect a pathophysiological brain state. The investigators plan to carry out a phosphoproteomic study to determine the phosphorylation profile of plasma proteins in children with Down's syndrome, and identify potential DYRK1A-dependent pathophysiological mechanisms and biomarkers involved in the natural course of cognition in children with Down's syndrome.

Description:

During a consultation in their usual care department, dedicated to the care of children with trisomy 21, the children with trisomy 21 and their parents present will be informed about the study. An additional 2 mL of blood (from a blood sample taken as part of the consultation) will be drawn for the study by experienced nurses as part of their usual care. Plasma from this remaining volume will be fixed and analyzed to determine a phosphoproteomic profile. Multidimensional liquid chromatography with ultra-high resolution mass spectrometry will be used to analyze the native proteome and to obtain expression and phosphorylation levels of plasma proteins. Similar procedure will be performed on remaining blood samples of boys without genetic abnormality having blood analysis. Phosphoproteomic profiles of children with Down Syndrome and children without genetic abnormality will be compared to identify specific biomarkers of Down Syndrome.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: September 2024
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 6 Years to 12 Years

Eligibility

Inclusion Criteria:

• Clinical diagnosis of free and homogeneous trisomy 21,
• Body mass index (BMI): 15-25,
• Able to understand the study based on the pictorial information leaflet and give agreement/assent to participate,
• Parent present on the day of the visit to validate their child's consent/assent, if applicable.

Exclusion Criteria:

• Celiac disease,
• Autoimmune dysthyroidism,
• Type I autoimmune diabetes,
• Alopecia,
• Other autoimmune diseases,
• Current infectious pathology,
• History of infantile spasms,
• Autism spectrum disorders,
• Epilepsy,
• Central nervous system infections,
• Leukemia not in remission,
• Anti-inflammatory treatments (NSAIDs, local or systemic corticosteroids).

Related Conditions & MeSH terms

• Down Syndrome
• Syndrome

Intervention

Biological:
• Blood sample
Recovery of plasma from the bottom of a blood collection tube.

Locations

Country	Name	City	State
France	CHU Grenoble	Grenoble
France	Hospices Civils de Lyon	Lyon
France	Institut Jérôme Lejeune	Paris
France	CHU Rennes	Rennes
France	CHU Saint-Etienne	Saint-Etienne

Sponsors (3)

Lead Sponsor	Collaborator
Perha Pharmaceuticals	Göteborg University, Proteas Bioanalytics

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phosphoproteomic profile	The main objective is to determine a phosphoproteomic signature characteristic of the pathophysiological state of trisomy 21. Plasma protein phosphorylation profiles will be analyzed using the Proteas Bioanalytics Inc. platform on blood samples taken from children with trisomy 21, and compared with the phosphorylation profiles of children without trisomy 21 of the same age and sex. Analysis and comparison of trisomy and non-trisomy phosphorylation profiles will reveal a signature characteristic of trisomy 21, potentially reflected by significant differences in plasma protein phosphorylation levels (some of which may be of cerebral origin).	6 months
Secondary	Identification of brain proteins	To determine whether the phosphoproteomic profiles characteristic of trisomy 21 make it possible to identify brain proteins (exosomes),	6 months
Secondary	Impact of environnement on phosphoproteomic profile	To determine whether the differences potentially observed between the phosphoproteomic profiles of children with and without trisomy 21 correlate with the biological and socio-epidemiological data of children with trisomy 21,	6 months
Secondary	Impact of DYRK1A on Down Syndrome specific proteomic profile	Determine whether the differences potentially observed between the phosphoproteomic profiles of children with and without trisomy 21 are correlated with the level of DYRK1A expression,	6 months