NCT02455089

Brief 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
143

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Jun 2015

Longer than P75 for not_applicable

Geographic Reach
1 country

7 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 21, 2015

Completed
1 month until next milestone

First Posted

Study publicly available on registry

May 27, 2015

Completed
5 days until next milestone

Study Start

First participant enrolled

June 1, 2015

Completed
2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2018

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2019

Completed
Last Updated

February 21, 2019

Status Verified

February 1, 2019

Enrollment Period

2.7 years

First QC Date

April 21, 2015

Last Update Submit

February 20, 2019

Conditions

Lupus Erythematosus

Keywords

FlareTherapeutic adjustmentsBiological MarkerImmunologic MarkerPrognosis

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (2)

  • Prognosis score of SLE flare occurence

    Measured every 3 months, up to 1 year (5 blood samples).The Last result before a SLE flare occurence will be used.

  • Pro-inflammatory cytokine blood level.

    Measured every 3 months, up to 1 year (5 blood samples).

Other Outcomes (2)

  • GADD34 RNA level in each mononuclear blood cells (B cells, T cells and monocytes).

    Measured once at the 2nd visit (3 months after the inclusion).

  • GADD34 RNA level in non-mononuclear blood cells

    Measured once at the 2nd visit (3 months after the inclusion).

Study Arms (1)

Test group

EXPERIMENTAL

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

Other: GADD34 RNA level measurement.

Interventions

GADD34 RNA level measurement.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.

Also known as: Experimental: Test group
Test group

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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).

You may not qualify if:

  • 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).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (7)

CHU Grenoble

Grenoble, 38000, France

Location

groupement hospitalier mutualiste de Grenoble

Grenoble, 38000, France

Location

Hopital européen de Marseille

Marseille, 13003, France

Location

CHU Marseille

Marseille, 13005, France

Location

CHR Annecy Genevois

Metz-Tessy, 74370, France

Location

CHU Lyon sud

Pierre-Bénite, 69310, France

Location

CHU Saint Etienne

Saint-Etienne, 42000, France

Location

Related Publications (10)

  • 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.

    PMID: 23584529RESULT

  • 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.

    PMID: 22615568RESULT

  • 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.

    PMID: 22315398RESULT

  • 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.

    PMID: 23144449RESULT

  • 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.

    PMID: 20652065RESULT

  • 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.

    PMID: 11381086RESULT

  • 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.

    PMID: 23754628RESULT

  • 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.

    PMID: 12480667RESULT

  • 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.

    PMID: 22733998RESULT

  • 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.

    PMID: 23452295RESULT

Study Officials

  • Jean-Yves Cesbron, MD

    University Hospital of Grenoble, France.

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NA
Masking
NONE
Purpose
DIAGNOSTIC
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 21, 2015

First Posted

May 27, 2015

Study Start

June 1, 2015

Primary Completion

February 1, 2018

Study Completion

February 1, 2019

Last Updated

February 21, 2019

Record last verified: 2019-02

Data Sharing

IPD Sharing
Will share

No data will be be shared with non associated investigator till publication. Possibility to share after publication, through formol requirement adressed to Grenoble hospital administration (AccueilRecherche@chu-grenoble.fr)

Locations

FR(7)