SarcoidosisSARCFAMNCT02829853
Clinical and Genetic Study of Familial Sarcoidosis (SARCFAM)
An observational study of Sarcoidosis, run by Hospices Civils de Lyon at 1 site in France.
Trial summary
Major impacts of air pollution are lung diseases such as granulomatous diseases and mainly sarcoidosis. Understanding the respective role of inorganic / nanoparticles and genetic background in these chronic diseases is a major challenge for the management of patients and prevention strategies. Read more about this study
- Who is it for?
- Ages 8 to 80 years
- Conditions the study is for
- Sarcoidosis
- What is being tested?
- Genetic analysis by SANGER and WHOLE EXOME NEXT GENERATION SEQUENCING
- How many people
- 800 participants
- Where
- 1 siteFrance
- Study dates
- Jan 2008to Sep 2016
- Phase
- Observational
- 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 8 to 80 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: patient affected by sarcoidosis
Who may be able to join
- patient affected by sarcoidosis, as defined by clinical criteria such as : chest X-ray staging, pulmonary function tests, biological variables: serum calcium and creatinine, bronchial alveolar lavage cell count and when available, an histological confirmation of the granuloma by biopsy. The disease may be expressed initially as uveitis, cutaneous or other anatomical sites involvement, which must be also confirmed as sarcoidosis-related granuloma by competent pathologists.
Who cannot join
- Any other disease suggesting sarcoidosis and expressed by similar symptoms, as for ex. hilar lymphadenopathy, other forms of uveitis, restrictive pulmonary syndromes .. etc ….
- Any patients for which the follow-up was not available over the 8 year program of the GSF SARCFAM
- age < 8 years old or > 80 years old
Trial locations and contacts
1 site in 1 country.
Yves Pacheco contact
France1 site, 1 recruiting
- Recruiting
Hospices Civils de Lyon / Hopital Edouard Herriot
Lyon, 69003
Yves Pacheco, yves.pacheco@univ-lyon1.fr
About this study
Major impacts of air pollution are lung diseases such as granulomatous diseases and mainly sarcoidosis. Understanding the respective role of inorganic / nanoparticles and genetic background in these chronic diseases is a major challenge for the management of patients and prevention strategies. Granulomas are characterized by giant epithelioid and multinucleated cells, reflecting a severe disturbance in immunological pathways induced both by toxic exposure and genetic predisposition. Previous studies demonstrated that professional environmental context and acute exposures (the World Trade Center disaster) to micro/nanoparticles have a pathogenic impact with a sharp increase in sarcoidosis. Sarcoidosis is a multifactorial disease occurring in a genetically vulnerable context. Many gene variants have been linked to an increased odds-ratio of the disease, such BTNL2, CCDC88B, ANNEXIN A11 involved in regulation of T-cell activation and maturation pathways. We have contributed since 2008 to a national cohort (GSF, 28 centers) of ≈ 800 sarcoidosis patients with familial and sporadic presentation of the disease. This collection has been an exceptional (and worldwide unique) tool for the implementation of an exhaustive clinical database on sarcoidosis, modelling of disease evolution and identification of clinical / genetic criteria differentiating sporadic and familial forms.
The main goals of the project are:
- Completion of the genetic data in order to establish a pattern of gene variants segregating with familial forms of the disease, compared to sporadic one. This will be done by WES (WHOLE EXOME) analysis on the previously collected DNA samples. The informed consent for the patients included the information about the BTNL2 gene, which has been already tested since 2008, and related genes connected to immune pathways, thus allowing a unambiguous information about the research finality of the project.
- Completion of the clinical data about each patient, in cooperation with the GSF network, management of the database established since 2008. The data collected are those which are commonly detailed in the normal follow-up of the patients. The project do not include any new interventions on the patient (neither radiological or invasive tests).
- Specific biological studies might be done on the white blood cells of the patients, and might need in such cases a new blood sampling, both in patients and first degree related healthy controls. Theses specific studies will be presented to an ethical committee (CCP) in order to validate the feasibility in term of 'new intervention' on the cohort. The samples collected will be at the same volume of a classical blood sampling (2*7 ml).
- Any other projects, submitted to the GSF network will needed a specific registration and ethical committee validation.
- Conditions
- Sarcoidosis
- Being tested
- Genetic analysis by SANGER and WHOLE EXOME NEXT GENERATION SEQUENCING
- Keywords
- SARCOIDOSIS, GRANULOMA DISEASES, GENETICS, PREDISPOSITION, EXOME (WES-NGS)
- Medical subject headings
- Sarcoidosis, Disease Susceptibility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Genetic analysis by SANGER and WHOLE EXOME NEXT GENERATION SEQUENCINGGenetic
Patients with sarcoidosis patients are monitored in the regular follow-up in one of 28 GSF clinical centers. Blood sampling was performed in two 5ml classical heparinized tube, as used for red/white/platelets blood cells analysis. The patients receive complete information on the SARCFAM protocol and sign an informed consent stating that the genetic study will be conducted on the BTNL2 gene and genes related to immunity, including loci other than BTNL2.DNA was extracted from a 1-5 ml sample of blood and stored in frozen conditions until analysis. Genomic DNA is captured using Agilent in-solution enrichment methodology (Human Clinical Research Exome, Agilent) with their biotinylated oligonucleotides probes library, followed by paired-end 75 bases massively parallel sequencing on Illumina HiSEQ 400. For each genomic position, the exomic frequencies (Homo \& HTZ) are determined from all the exomes already sequenced and/or the exome results provided by 1000G, EVS, HapMap database.
| Study group | Role | What they receive |
|---|---|---|
| sporadic cases (SP) | Sporadic cases are defined as patients diagnosed for sarcoidosis, for which the familial history did not reveal any other cases, whatever the relative degree is: 1, 2, 3 or 4. The clinical follow-up and the genetic studies performed in the frame of this project are the same as for the familial group. During the regular follow-up, patients are regularly questioned about the putative occurrence of the disease in their family, and if such a situation occurred, the patient (and his relative) may change from the SP to the familial (FAM) group. In blood samples, genetic analysis by SANGER and WHOLE EXOME NEXT GENERATION SEQUENCING will be done. Receives: Genetic: Genetic analysis by SANGER and WHOLE EXOME NEXT GENERATION SEQUENCING | |
| familial cases (FAM) | Familial cases are defined as patients diagnosed for sarcoidosis with a first and/or second degree relative parent also affected by a well-proven sarcoidosis syndrome. More than 70% of SARCFAM families included two first-degree affected individuals, with both a vertical or horizontal transmission. The Mendelian trait seems to be autosomal dominant. 20 to 30% of the families consists of 3, 4 or more cases, with a subset of families including more than 5 cases. Patients are managed as for the sporadic one, and in such families, an informed consent was also provided with a clear explanation on the complexity of the genetic background of the disease. In blood samples, genetic analysis by SANGER and WHOLE EXOME NEXT GENERATION SEQUENCING will be done. Receives: Genetic: Genetic analysis by SANGER and WHOLE EXOME NEXT GENERATION SEQUENCING |
What is being measured
The primary outcome is the main question the study is designed to answer.
number of mutations founded in the IL34-TIAM gene
Determination of the number of mutations founded in the IL34-TIAM gene which has been described as involved in the formation of granuloma, a key lesion of sarcoidosis
Measured: Day 0
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2016 (estimated)
- Study startJan 2008
- Primary completionSep 2016 (estimated)
- Study completionSep 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for SarcoidosisStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 800 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02829853
- Sponsor's protocol ID
- D50604
- Acronym
- SARCFAM
- Status last verified
- Jul 2016
- First submitted
- 4 Jul 2016
- Last updated
- 12 Jul 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
Calender A, Rollat Farnier PA, Buisson A, Pinson S, Bentaher A, Lebecque S, Corvol H, Abou Taam R, Houdouin V, Bardel C, Roy P, Devouassoux G, Cottin V, Seve P, Bernaudin JF, Lim CX, Weichhart T, Valeyre D, Pacheco Y, Clement A, Nathan N; in the frame of GSF (Groupe Sarcoidose France). Whole exome sequencing in three families segregating a pediatric case of sarcoidosis. BMC Med Genomics. 2018 Mar 6;11(1):23. doi: 10.1186/s12920-018-0338-x.
PubMed 29510755
Study at a glance
From the registry record, last updated by the sponsor on 12 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical and Genetic Study of Familial Sarcoidosis (SARCFAM)
- ClinicalTrials.gov ID
- NCT02829853
- Acronym / sponsor ID
- SARCFAM / D50604
- Conditions
- Sarcoidosis
- Keywords
- SARCOIDOSIS, GRANULOMA DISEASES, GENETICS, PREDISPOSITION, EXOME (WES-NGS)
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 800 participants (estimated)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- Jan 2008
- Primary completion
- Sep 2016 (estimated)
- Study completion
- Sep 2016 (estimated)
- First posted
- 12 Jul 2016 (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.
Major impacts of air pollution are lung diseases such as granulomatous diseases and mainly sarcoidosis. Understanding the respective role of inorganic / nanoparticles and genetic background in these chronic diseases is a major challenge for the management of patients and prevention strategies. Granulomas are characterized by giant epithelioid and multinucleated cells, reflecting a severe disturbance in immunological pathways induced both by toxic exposure and genetic predisposition. Previous studies demonstrated that professional environmental context and acute exposures (the World Trade Center disaster) to micro/nanoparticles have a pathogenic impact with a sharp increase in sarcoidosis. Sarcoidosis is a multifactorial disease occurring in a genetically vulnerable context. Many gene variants have been linked to an increased odds-ratio of the disease, such BTNL2, CCDC88B, ANNEXIN A11 involved in regulation of T-cell activation and maturation pathways. We have contributed since 2008 to a national cohort (GSF, 28 centers) of ≈ 800 sarcoidosis patients with familial and sporadic presentation of the disease. This collection has been an exceptional (and worldwide unique) tool for the implementation of an exhaustive clinical database on sarcoidosis, modelling of disease evolution and identification of clinical / genetic criteria differentiating sporadic and familial forms.
The main goals of the project are:
- Completion of the genetic data in order to establish a pattern of gene variants segregating with familial forms of the disease, compared to sporadic one. This will be done by WES (WHOLE EXOME) analysis on the previously collected DNA samples. The informed consent for the patients included the information about the BTNL2 gene, which has been already tested since 2008, and related genes connected to immune pathways, thus allowing a unambiguous information about the research finality of the project.
- Completion of the clinical data about each patient, in cooperation with the GSF network, management of the database established since 2008. The data collected are those which are commonly detailed in the normal follow-up of the patients. The project do not include any new interventions on the patient (neither radiological or invasive tests).
- Specific biological studies might be done on the white blood cells of the patients, and might need in such cases a new blood sampling, both in patients and first degree related healthy controls. Theses specific studies will be presented to an ethical committee (CCP) in order to validate the feasibility in term of 'new intervention' on the cohort. The samples collected will be at the same volume of a classical blood sampling (2*7 ml).
- Any other projects, submitted to the GSF network will needed a specific registration and ethical committee validation.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| sporadic cases (SP) | – | Genetic: Genetic analysis by SANGER and WHOLE EXOME NEXT GENERATION SEQUENCINGSporadic cases are defined as patients diagnosed for sarcoidosis, for which the familial history did not reveal any other cases, whatever the relative degree is: 1, 2, 3 or 4. The clinical follow-up and the genetic studies performed in the frame of this project are the same as for the familial group. During the regular follow-up, patients are regularly questioned about the putative occurrence of the disease in their family, and if such a situation occurred, the patient (and his relative) may change from the SP to the familial (FAM) group. In blood samples, genetic analysis by SANGER and WHOLE EXOME NEXT GENERATION SEQUENCING will be done. |
| familial cases (FAM) | – | Genetic: Genetic analysis by SANGER and WHOLE EXOME NEXT GENERATION SEQUENCINGFamilial cases are defined as patients diagnosed for sarcoidosis with a first and/or second degree relative parent also affected by a well-proven sarcoidosis syndrome. More than 70% of SARCFAM families included two first-degree affected individuals, with both a vertical or horizontal transmission. The Mendelian trait seems to be autosomal dominant. 20 to 30% of the families consists of 3, 4 or more cases, with a subset of families including more than 5 cases. Patients are managed as for the sporadic one, and in such families, an informed consent was also provided with a clear explanation on the complexity of the genetic background of the disease. In blood samples, genetic analysis by SANGER and WHOLE EXOME NEXT GENERATION SEQUENCING will be done. |
Who may qualify
- Ages
- 8 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- patient affected by sarcoidosis
Key inclusion criteria (1 listed)
- patient affected by sarcoidosis, as defined by clinical criteria such as : chest X-ray staging, pulmonary function tests, biological variables: serum calcium and creatinine, bronchial alveolar lavage cell count and when available, an histological confirmation of the granuloma by biopsy. The disease may be expressed initially as uveitis, cutaneous or other anatomical sites involvement, which must be also confirmed as sarcoidosis-related granuloma by competent pathologists.
Key exclusion criteria (3 listed)
- Any other disease suggesting sarcoidosis and expressed by similar symptoms, as for ex. hilar lymphadenopathy, other forms of uveitis, restrictive pulmonary syndromes .. etc ….
- Any patients for which the follow-up was not available over the 8 year program of the GSF SARCFAM
- age < 8 years old or > 80 years old
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 |
|---|---|---|
| Genetic analysis by SANGER and WHOLE EXOME NEXT GENERATION SEQUENCINGPatients with sarcoidosis patients are monitored in the regular follow-up in one of 28 GSF clinical centers. Blood sampling was performed in two 5ml classical heparinized tube, as used for red/white/platelets blood cells analysis. The patients receive complete information on the SARCFAM protocol and sign an informed consent stating that the genetic study will be conducted on the BTNL2 gene and genes related to immunity, including loci other than BTNL2.DNA was extracted from a 1-5 ml sample of blood and stored in frozen conditions until analysis. Genomic DNA is captured using Agilent in-solution enrichment methodology (Human Clinical Research Exome, Agilent) with their biotinylated oligonucleotides probes library, followed by paired-end 75 bases massively parallel sequencing on Illumina HiSEQ 400. For each genomic position, the exomic frequencies (Homo \& HTZ) are determined from all the exomes already sequenced and/or the exome results provided by 1000G, EVS, HapMap database. | Genetic | familial cases (FAM), sporadic cases (SP) |
Primary outcome
number of mutations founded in the IL34-TIAM gene
Time frame: Day 0
Determination of the number of mutations founded in the IL34-TIAM gene which has been described as involved in the formation of granuloma, a key lesion of sarcoidosis
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jul 2016.
- Derived from this study: PubMed 29510755Calender A, Rollat Farnier PA, Buisson A, Pinson S, Bentaher A, Lebecque S, Corvol H, Abou Taam R, Houdouin V, Bardel C, Roy P, Devouassoux G, Cottin V, Seve P, Bernaudin JF, Lim CX, Weichhart T, Valeyre D, Pacheco Y, Clement A, Nathan N; in the frame of GSF (Groupe Sarcoidose France). Whole exome sequencing in three families segregating a pediatric case of sarcoidosis. BMC Med Genomics. 2018 Mar 6;11(1):23. doi: 10.1186/s12920-018-0338-x.
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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.
Yves Pacheco contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Sarcoidosis, run by Hospices Civils de Lyon at 1 site 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 1 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: status not confirmed, as of the sponsor's last update on 12 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Alain Calender (33 (0)4 72 11 73 80, alain.calender@chu-lyon.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
number of mutations founded in the IL34-TIAM gene (time frame: Day 0). 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 NCT02829853, which also lists 1 linked publication.
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 12 Jul 2016.