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

NCT ID: NCT02455089

Last Updated: 2019-02-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

143 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-06-30

Study Completion Date

2019-02-28

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Lupus Erythematosus

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

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Test group

250 SLE patients : All SLE patients included in the study. Intervention : Blood analysis including GADD34 RNA level measurement every 3 months up to 1 year.

They will provided a blood sample every 3 months during a year. The result of GADD34 RNA level in mononuclear blood cells will be correlated to the clinical assessment of a SLE flare during the next 3 months.

A flare occurence will the group

Group Type EXPERIMENTAL

GADD34 RNA level measurement.

Intervention Type OTHER

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.

Interventions

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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.

Intervention Type OTHER

Other Intervention Names

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Experimental: Test group

Eligibility Criteria

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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).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University Hospital, Grenoble

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jean-Yves Cesbron, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital of Grenoble, France.

Locations

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CHU Grenoble

Grenoble, , France

Site Status

groupement hospitalier mutualiste de Grenoble

Grenoble, , France

Site Status

Hopital européen de Marseille

Marseille, , France

Site Status

CHU Marseille

Marseille, , France

Site Status

CHR Annecy Genevois

Metz-Tessy, , France

Site Status

CHU Lyon sud

Pierre-Bénite, , France

Site Status

CHU Saint Etienne

Saint-Etienne, , France

Site Status

Countries

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France

References

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Claudio 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.

Reference Type RESULT
PMID: 23584529 (View on PubMed)

Clavarino G, Claudio 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-beta production and participates in the control of Chikungunya virus infection. PLoS Pathog. 2012;8(5):e1002708. doi: 10.1371/journal.ppat.1002708. Epub 2012 May 17.

Reference Type RESULT
PMID: 22615568 (View on PubMed)

Clavarino G, Claudio 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 dendritic cells. Proc Natl Acad Sci U S A. 2012 Feb 21;109(8):3006-11. doi: 10.1073/pnas.1104491109. Epub 2012 Feb 6.

Reference Type RESULT
PMID: 22315398 (View on PubMed)

Costedoat-Chalumeau N, Galicier L, Aumaitre O, Frances C, Le Guern V, Liote 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, Sacre K, Fain O, Stirnemann J, Cacoub P, Jallouli M, Leroux G, Cohen-Bittan J, Tanguy ML, Hulot JS, Lechat P, Musset L, Amoura Z, Piette JC; Group PLUS. Hydroxychloroquine in systemic lupus erythematosus: results of a French multicentre controlled trial (PLUS Study). Ann Rheum Dis. 2013 Nov;72(11):1786-92. doi: 10.1136/annrheumdis-2012-202322. Epub 2012 Nov 10.

Reference Type RESULT
PMID: 23144449 (View on PubMed)

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.

Reference Type RESULT
PMID: 20652065 (View on PubMed)

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. doi: 10.1083/jcb.153.5.1011.

Reference Type RESULT
PMID: 11381086 (View on PubMed)

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 trials. Arthritis Rheum. 2013 Aug;65(8):2143-53. doi: 10.1002/art.37995.

Reference Type RESULT
PMID: 23754628 (View on PubMed)

Ronnelid 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 B cell hyperactivity in SLE. Ann Rheum Dis. 2003 Jan;62(1):37-42. doi: 10.1136/ard.62.1.37.

Reference Type RESULT
PMID: 12480667 (View on PubMed)

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.

Reference Type RESULT
PMID: 22733998 (View on PubMed)

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.

Reference Type RESULT
PMID: 23452295 (View on PubMed)

Other Identifiers

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2015-A00493-46

Identifier Type: OTHER

Identifier Source: secondary_id

38RC15.010

Identifier Type: -

Identifier Source: org_study_id

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