Prognosis Assessment of the Increase of GADD34 Gene Expression for Patient Suffering From Systemic Lupus Erythematosus

Lupus Erythematosus Clinical Trial

— GADD34-LES  

Official title:

Prognosis Assessment of the Increase of GADD34 Gene Expression for Patient Suffering From Systemic Lupus Erythematosus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02455089
• Other study ID #: 38RC15.010
• Secondary ID: 2015-A00493-46
• Status: Completed
• Phase: N/A
• Start date: June 2015
• Est. completion date: February 2019

Study information

• Verified date: February 2019
• Source: University Hospital, Grenoble
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Given that GADD34 has been described as a potential key regulator of pro-inflammatory cytokine production in human and elevated blood marker in SLE patients, this study aim to prove that the GADD34 RNA level in mononuclear blood cells can be used as a prognostic marker to assess the risk of SLE flare.

Description:

Systemic lupus erythematosus (SLE) has a prevalence estimated between 1 and 6 per 10000 individuals and concerns over 30 000 patients in France for example. As of today, there isn't any reliable specific blood analysis that can be used to assess the prognosis of SLE, that means predict a SLE flare. The discovery of such a blood test could allow a better patients' monitoring in order to help doctors to better adapt treatments (lowering background treatments when they are not needed and increase them ahead of a potential flare when the risk assessment raises).

In SLE patients, a recent study shows elevated levels of GADD34 RNA in mononuclear blood cells : higher than twice the control levels for 36 of the 60 SLE patients and ten times higher than the control levels for 13 of the 60 SLE patients.

Given that GADD34 has been described as a potential key regulator of pro-inflammatory cytokine production in human and elevated blood marker in SLE patients, this study aim to prove that the GADD34 RNA level in mononuclear blood cells can be used as a prognostic marker to assess the risk of SLE flare.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 143
• Est. completion date: February 2019
• Est. primary completion date: February 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

• Inclusion Criteria:

• man and women over 18 Years old.

• suffering from SLE (American College of Rheumatology criteria).

• without SLE flare for 3 months.

• with a signed consent and social security affiliation (required in France).

• Exclusion Criteria:

• Viral infection within 15 days.

• Other chronic inflammatory disease.

• People with special protection (defined in articles : L1121- §5-8 et articles L3212-§1-3 of French health care law).

Related Conditions & MeSH terms

• Lupus Erythematosus
• Lupus Erythematosus, Systemic

Intervention

Other:
• GADD34 RNA level measurement.
Blood analysis including GADD34 RNA level measurement is performed every 3 months up to 1 year for SLE patients. A modal including physical exam, standard biological results and GADD34 RNA level is correlated to a SLE flare occurence in the next 3 months.

Locations

Country	Name	City	State
France	CHU Grenoble	Grenoble
France	groupement hospitalier mutualiste de Grenoble	Grenoble
France	CHU Marseille	Marseille
France	Hopital européen de Marseille	Marseille
France	CHR Annecy Genevois	Metz-Tessy
France	CHU Lyon sud	Pierre-Bénite
France	CHU Saint Etienne	Saint Etienne

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Grenoble

Country where clinical trial is conducted

France, 

References & Publications (10)

Cláudio N, Dalet A, Gatti E, Pierre P. Mapping the crossroads of immune activation and cellular stress response pathways. EMBO J. 2013 May 2;32(9):1214-24. doi: 10.1038/emboj.2013.80. Epub 2013 Apr 12. Review. — View Citation

Clavarino G, Cláudio N, Couderc T, Dalet A, Judith D, Camosseto V, Schmidt EK, Wenger T, Lecuit M, Gatti E, Pierre P. Induction of GADD34 is necessary for dsRNA-dependent interferon-ß production and participates in the control of Chikungunya virus infecti — View Citation

Clavarino G, Cláudio N, Dalet A, Terawaki S, Couderc T, Chasson L, Ceppi M, Schmidt EK, Wenger T, Lecuit M, Gatti E, Pierre P. Protein phosphatase 1 subunit Ppp1r15a/GADD34 regulates cytokine production in polyinosinic:polycytidylic acid-stimulated dendri — View Citation

Costedoat-Chalumeau N, Galicier L, Aumaître O, Francès C, Le Guern V, Lioté F, Smail A, Limal N, Perard L, Desmurs-Clavel H, Boutin du LT, Asli B, Kahn JE, Pourrat J, Sailler L, Ackermann F, Papo T, Sacré K, Fain O, Stirnemann J, Cacoub P, Jallouli M, Ler — View Citation

Niewold TB, Clark DN, Salloum R, Poole BD. Interferon alpha in systemic lupus erythematosus. J Biomed Biotechnol. 2010;2010:948364. doi: 10.1155/2010/948364. Epub 2010 Jun 29. Review. — View Citation

Novoa I, Zeng H, Harding HP, Ron D. Feedback inhibition of the unfolded protein response by GADD34-mediated dephosphorylation of eIF2alpha. J Cell Biol. 2001 May 28;153(5):1011-22. — View Citation

Petri MA, van Vollenhoven RF, Buyon J, Levy RA, Navarra SV, Cervera R, Zhong ZJ, Freimuth WW; BLISS-52 and BLISS-76 Study Groups. Baseline predictors of systemic lupus erythematosus flares: data from the combined placebo groups in the phase III belimumab — View Citation

Rönnelid J, Tejde A, Mathsson L, Nilsson-Ekdahl K, Nilsson B. Immune complexes from SLE sera induce IL10 production from normal peripheral blood mononuclear cells by an FcgammaRII dependent mechanism: implications for a possible vicious cycle maintaining — View Citation

Wang S, Kaufman RJ. The impact of the unfolded protein response on human disease. J Cell Biol. 2012 Jun 25;197(7):857-67. doi: 10.1083/jcb.201110131. Review. — View Citation

Yap DY, Lai KN. The role of cytokines in the pathogenesis of systemic lupus erythematosus - from bench to bedside. Nephrology (Carlton). 2013 Apr;18(4):243-55. doi: 10.1111/nep.12047. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	GADD34 RNA level in each mononuclear blood cells (B cells, T cells and monocytes).	GADD34 RNA level is measured respectively in B cells, T cells and monocytes and is compared with each other.; RNA levels have no unit,they are rates compared with a housekeeping gene RNA level as unit. This outcome is measured only for 30 patients.	Measured once at the 2nd visit (3 months after the inclusion).
Other	GADD34 RNA level in non-mononuclear blood cells	GADD34 RNA level is measured respectively in non-mononuclear blood cells and is compared with GADD34 RNA level in mononuclear blood cells.; RNA levels have no unit,they are rates compared with a housekeeping gene RNA level as unit. This outcome is measured only for 30 patients.	Measured once at the 2nd visit (3 months after the inclusion).
Primary	GADD34 RNA level	GADD34 RNA level in mononuclear blood cells in the last 3 months before a SLE flare occurence.; RNA levels have no unit,they are rates compared with a housekeeping gene RNA level as unit.; To avoid any bias in primary outcome, SLE Flare occurence is assessed with both patient and investigator blinded from Gadd34 RNA level.	Measured every 3 months, up to 1 year (5 blood samples).The Last result before a SLE flare occurence will be used.
Secondary	Prognosis score of SLE flare occurence	Prognosis score of SLE flare occurence using a modal including GADD34 RNA increase, SLEDAI score and Physician Global Assessment (PGA).; This modal is compared to the gold standard modal which use only PGA and SLEDAI Score in term of sensibility and specificity.	Measured every 3 months, up to 1 year (5 blood samples).The Last result before a SLE flare occurence will be used.
Secondary	Pro-inflammatory cytokine blood level.	Correlation between GADD34 RNA increase or decrease and interferon-alpha, interferon-beta, interleukin-6 and interleukine-17 levels.	Measured every 3 months, up to 1 year (5 blood samples).