Lupus ErythematosusGADD34-LESNCT02455089
Prognosis Assessment of the Increase of GADD34 Gene Expression for Patient Suffering From Systemic Lupus Erythematosus
A study testing GADD34 RNA level measurement. in people with Lupus Erythematosus, run by University Hospital, Grenoble at 7 sites in France.
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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Lupus Erythematosus
- What is being tested?
- GADD34 RNA level measurement.
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 143 participants
- Where
- 7 sitesFrance
- Study dates
- Jun 2015to Feb 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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).
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
France7 sites
CHU Grenoble
Grenoble, 38000
groupement hospitalier mutualiste de Grenoble
Grenoble, 38000
Hopital européen de Marseille
Marseille, 13003
CHU Marseille
Marseille, 13005
CHR Annecy Genevois
Metz-Tessy, 74370
CHU Lyon sud
Pierre-Bénite, 69310
CHU Saint Etienne
Saint-Etienne, 42000
About this study
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.
Read the detailed 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.
- Conditions
- Lupus Erythematosus
- Being tested
- GADD34 RNA level measurement.
- Keywords
- Flare, Therapeutic adjustments, Biological Marker, Immunologic Marker, Prognosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GADD34 RNA level measurement.Other
Also called Experimental: Test group
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Other: GADD34 RNA level measurement. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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: 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
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: 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.
Correlation between GADD34 RNA increase or decrease and interferon-alpha, interferon-beta, interleukin-6 and interleukine-17 levels.
Measured: Measured every 3 months, up to 1 year (5 blood samples).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 May 2015 (estimated)
- Study startJun 2015
- Primary completionFeb 2018
- Study completionFeb 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Lupus ErythematosusStudies of the same condition, open and under way.
- More trials run by University Hospital, GrenobleThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 143 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Grenoble
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jean-Yves Cesbron, MD, Principal investigator, University Hospital of Grenoble, France.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02455089
- Sponsor's protocol ID
- 38RC15.010
- Other IDs
- 2015-A00493-46
- Acronym
- GADD34-LES
- Status last verified
- Feb 2019
- First submitted
- 21 Apr 2015
- Last updated
- 21 Feb 2019
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: 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)
Publications
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.
PubMed 23584529Clavarino 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.
PubMed 22615568Clavarino 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.
PubMed 22315398Costedoat-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.
PubMed 23144449Niewold 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.
PubMed 20652065Novoa 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.
PubMed 11381086Petri 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.
PubMed 23754628Ronnelid 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.
PubMed 12480667Wang 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.
PubMed 22733998Yap 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.
PubMed 23452295
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prognosis Assessment of the Increase of GADD34 Gene Expression for Patient Suffering From Systemic Lupus Erythematosus
- ClinicalTrials.gov ID
- NCT02455089
- Acronym / sponsor ID
- GADD34-LES / 38RC15.010
- Conditions
- Lupus Erythematosus
- Keywords
- Flare, Therapeutic adjustments, Biological Marker, Immunologic Marker, Prognosis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 143 participants (actual)
- Lead sponsor
- University Hospital, GrenobleUniversity, hospital or other
- Study start
- Jun 2015 (actual)
- Primary completion
- Feb 2018 (actual)
- Study completion
- Feb 2019 (actual)
- First posted
- 27 May 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Test group | Experimental | Other: GADD34 RNA level measurement.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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
Key exclusion criteria (3 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GADD34 RNA level measurement.Also: Experimental: Test groupBlood 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. | Other | Test group |
Primary outcome
GADD34 RNA level
Time frame: Measured every 3 months, up to 1 year (5 blood samples).The Last result before a SLE flare occurence will be used.
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.
2 secondary outcomes
Prognosis score of SLE flare occurence
Time frame: 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.
Time frame: Measured every 3 months, up to 1 year (5 blood samples).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2019.
- Results publication: PubMed 23584529Claudio 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.
- Results publication: PubMed 22615568Clavarino 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.
- Results publication: PubMed 22315398Clavarino 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.
- Results publication: PubMed 23144449Costedoat-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.
- Results publication: PubMed 20652065Niewold 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.
- Results publication: PubMed 11381086Novoa 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.
- Results publication: PubMed 23754628Petri 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.
- Results publication: PubMed 12480667Ronnelid 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.
- Results publication: PubMed 22733998Wang 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.
- Results publication: PubMed 23452295Yap 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.
- Individual participant dataSharing planned: Yes. 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)
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jean-Yves Cesbron, MD principal investigator
University Hospital of Grenoble, France.
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing GADD34 RNA level measurement. in people with Lupus Erythematosus, run by University Hospital, Grenoble at 7 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
GADD34 RNA level (time frame: Measured every 3 months, up to 1 year (5 blood samples).The Last result before a SLE flare occurence will be used.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02455089, which also lists 10 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Feb 2019.