Graft Versus Host DiseaseE-mageNCT02707354
Early Detection of Mucosal Abnormalities in Graft-versus-host Disease
A study testing Probe based confocal laser endomicroscopy (Cellvizio) in people with Graft Versus Host Disease, run by Nantes University Hospital at 1 site in France.
Trial summary
Gastro-intestinal graft versus host disease (GVHD) is a major source of morbidity and mortality amongst allogenic hematopoietic stem cell transplantation (Allo-HSCT). The diagnosis is based on histological findings that involve colonic biopsies with a risk of bleeding, especially in case of thrombocytopenia. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Graft Versus Host Disease
- What is being tested?
- Probe based confocal laser endomicroscopy (Cellvizio)
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteFrance
- Study dates
- 3 Jun 2016to 20 Aug 2018
- 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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient at risk for GVHD, i.e. undergoing HSCT for hematologic disorder
- Patient receiving a reduce intensity conditioning
- Aged 18 years or over
- Underlying hematologic disorder in complete remission
- Willing to participate after informed consent signed
Who cannot join
- Patient receiving a myeloablative conditioning regimen
- Patients receiving allo-HSCT from an haploidentical donor or an umbilical cord blood
- Patients receiving a second or beyond allo-HSCT
- Patient with the underlying hematologic disorder in relapse
- Patients having developed a GVHD before inclusion in the study
- Patients having developed engraftment syndrome
Show all 15Show fewer
- Patients receiving corticosteroid upper 0.5 mg/kg/d
- Patients with ongoing uncontrolled medical condition
- Prior history of allergy to fluorescein
- Renal dysfunction
- Suspected or documented bowel obstruction
- Known inflammatory bowel disease
- History of major abdominal intervention
- No contraception
- Breast-feeding or pregnancy
Trial locations and contacts
1 site in 1 country.
About this study
Gastro-intestinal graft versus host disease (GVHD) is a major source of morbidity and mortality amongst allogenic hematopoietic stem cell transplantation (Allo-HSCT). The diagnosis is based on histological findings that involve colonic biopsies with a risk of bleeding, especially in case of thrombocytopenia. Moreover the diagnosis is frequently made at a clinical stage of the disease, after the appearance of gastro-intestinal symptoms. Endo-microscopy is a novel endoscopic technique that allow "optical biopsies" during a conventional endoscopy and has proved its efficiency in several indications. In a pilot study the investigators showed that it had good sensibility and sensitivity compared to histology as gold standard. Therefore this study aim to identify endo-microscopic criteria allowing the early diagnosis of GHVD before its clinical manifestations.
Read the detailed description
The investigators propose a mini-invasive alternative technique to perform biopsies in the terminal part of the colon with rectosigmoidoscopy alone. Confocal laser endomicroscopy, either using an endoscope-based or a probe based technology , aims to decrease the number of standard biopsies and their associated risks, by providing real-time in situ microscopy. In a previous pilot study performed in 15 patients at the University hospital of Nantes, the investigators suggested that combining probe-based confocal laser endomicroscopy (pCLE) and wireless capsule endoscopy (WCE) could detect early mucosal abnormalities suggestive of GVHD and thus be part of a mini-invasive algorithm for early detection of GI-GVHD. However, in this study, the investigators showed that pCLE was a sensitive method for the early diagnosis of GVH with a sensibility of 85% and a specificity of 71.5%. These interesting results are however to put in question due to several reasons. First of all the pCLE criteria used to define a GVHD in this study were established with data stemming of literature in other validated indications such as the MIAMI score for the diagnosis of malignant biliary structures and therefore can turn out not to be as relevant as expected. Secondly the interpretations of the images obtained with pCLE were only interpreted by a single endoscopist who by the way wasn't blinded from the macroscopic appearance of eventual lesions during rectosigmoidoscopy resulting in a bias. Thirdly the number of patient as in a pilot study was probably not sufficient to evaluate the real sensibility and sensitivity of those new indication and technique for the early diagnosis of GVH. All together these observations lead us to the necessity of developing the promising results obtained previously and allow their realization by the creation of an innovating pCLE score : the E-mage score. The different criteria of the score will be established after the one defined in the pilot study reviewed by an expert committee combining anatomo-pathologists and endoscopists to be as objective as possible with quantitative and semi-quantitative assessments focusing particularly on crypt architecture, morphologic and dynamic criteria and fluorescein leakage with a cut off standing as no GVHD, likely GVHD or certain GVHD.
- Conditions
- Graft Versus Host Disease
- Being tested
- Probe based confocal laser endomicroscopy (Cellvizio)
- Keywords
- GVHD, confocal endomicroscopy
- Medical subject headings
- Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Probe based confocal laser endomicroscopy (Cellvizio)Device
The probe is a miniaturized microscope in the form of a fiber which is inserted through the endoscope and brought into contact with the mucosa. It thus allows for a "live virtual biopsy", that is to say, obtaining real-time microscopic virtual image of the mucosa. It requires an intra-veinous injection of 5 mL of 10% fluorescein diluted in 50 cc of saline serum. The images obtained during the examination will be recorded via the endomicroscopy console so that two endoscopists blinded from the macroscopic and histological findings can review the data.
| Study group | Role | What they receive |
|---|---|---|
| Probe based confocal laser endomicroscopy (Cellvizio) | Experimental | intra-veinous injection of 5 mL of 10% fluorescein diluted in 50 cc of saline serum. The images obtained during the examination will be recorded via the endomicroscopy console. Receives: Device: Probe based confocal laser endomicroscopy (Cellvizio) |
What is being measured
The primary outcome is the main question the study is designed to answer.
E-mage Score
The primary endpoint is the evaluation of E-mage score as a new way to detect the early occurrence of GVH amongst patient undergoing Allo-HSCT, considering its sensibility an sensitivity. The E-mage score will be constructed after an expert committee to define semiquantitative or quantitative criteria allowing the classification of pCLE lesions from no GVH to certain GVH. Those criteria will be set regarding the results of the pilot study. The pCLE images will be interpreted by two endoscopists used to pCLE images and blinded from macroscopic observations. Correlation between the E-mage score calculated for each patient and the gold standard histology will be evaluated and sensibility and specificity of the Emage score will be calculated.
Measured: Once for each patient between day 21 and day 28 after graft
Secondary outcomes (2)
new early paraclinical markers of GVH and correlation with the occurrence of GVHD
Identification of intestinal modifications (microbiota, AMP secretion, phenotype of the enteric nervous system cells, immune phenotype ) presented by each participant
Measured: up to 3 month after graft
GVHD physiopathology
Identification of intestinal modifications (microbiota, AMP secretion, phenotype of the enteric nervous system cells, immune phenotype ) presented by each participant
Measured: within one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Mar 2016 (estimated)
- Study start3 Jun 2016
- Primary completion20 Aug 2018
- Study completion20 Aug 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Graft Versus Host DiseaseStudies of the same condition, open and under way.
- More trials run by Nantes University HospitalThe 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
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nantes University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Emmanuel Coron, MD-PHD, Principal investigator, Nantes University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02707354
- Sponsor's protocol ID
- RC15_0327
- Acronym
- E-mage
- Status last verified
- Aug 2019
- First submitted
- 24 Feb 2016
- Last updated
- 29 Aug 2019
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Detection of Mucosal Abnormalities in Graft-versus-host Disease
- ClinicalTrials.gov ID
- NCT02707354
- Acronym / sponsor ID
- E-mage / RC15_0327
- Conditions
- Graft Versus Host Disease
- Keywords
- GVHD, confocal endomicroscopy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Nantes University HospitalUniversity, hospital or other
- Study start
- 3 Jun 2016 (actual)
- Primary completion
- 20 Aug 2018 (actual)
- Study completion
- 20 Aug 2018 (actual)
- First posted
- 14 Mar 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.
Gastro-intestinal graft versus host disease (GVHD) is a major source of morbidity and mortality amongst allogenic hematopoietic stem cell transplantation (Allo-HSCT). The diagnosis is based on histological findings that involve colonic biopsies with a risk of bleeding, especially in case of thrombocytopenia. Moreover the diagnosis is frequently made at a clinical stage of the disease, after the appearance of gastro-intestinal symptoms. Endo-microscopy is a novel endoscopic technique that allow "optical biopsies" during a conventional endoscopy and has proved its efficiency in several indications. In a pilot study the investigators showed that it had good sensibility and sensitivity compared to histology as gold standard. Therefore this study aim to identify endo-microscopic criteria allowing the early diagnosis of GHVD before its clinical manifestations.
Detailed description
The investigators propose a mini-invasive alternative technique to perform biopsies in the terminal part of the colon with rectosigmoidoscopy alone. Confocal laser endomicroscopy, either using an endoscope-based or a probe based technology , aims to decrease the number of standard biopsies and their associated risks, by providing real-time in situ microscopy. In a previous pilot study performed in 15 patients at the University hospital of Nantes, the investigators suggested that combining probe-based confocal laser endomicroscopy (pCLE) and wireless capsule endoscopy (WCE) could detect early mucosal abnormalities suggestive of GVHD and thus be part of a mini-invasive algorithm for early detection of GI-GVHD. However, in this study, the investigators showed that pCLE was a sensitive method for the early diagnosis of GVH with a sensibility of 85% and a specificity of 71.5%. These interesting results are however to put in question due to several reasons. First of all the pCLE criteria used to define a GVHD in this study were established with data stemming of literature in other validated indications such as the MIAMI score for the diagnosis of malignant biliary structures and therefore can turn out not to be as relevant as expected. Secondly the interpretations of the images obtained with pCLE were only interpreted by a single endoscopist who by the way wasn't blinded from the macroscopic appearance of eventual lesions during rectosigmoidoscopy resulting in a bias. Thirdly the number of patient as in a pilot study was probably not sufficient to evaluate the real sensibility and sensitivity of those new indication and technique for the early diagnosis of GVH. All together these observations lead us to the necessity of developing the promising results obtained previously and allow their realization by the creation of an innovating pCLE score : the E-mage score. The different criteria of the score will be established after the one defined in the pilot study reviewed by an expert committee combining anatomo-pathologists and endoscopists to be as objective as possible with quantitative and semi-quantitative assessments focusing particularly on crypt architecture, morphologic and dynamic criteria and fluorescein leakage with a cut off standing as no GVHD, likely GVHD or certain GVHD.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Probe based confocal laser endomicroscopy (Cellvizio) | Experimental | Device: Probe based confocal laser endomicroscopy (Cellvizio)intra-veinous injection of 5 mL of 10% fluorescein diluted in 50 cc of saline serum. The images obtained during the examination will be recorded via the endomicroscopy console. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patient at risk for GVHD, i.e. undergoing HSCT for hematologic disorder
- Patient receiving a reduce intensity conditioning
- Aged 18 years or over
- Underlying hematologic disorder in complete remission
- Willing to participate after informed consent signed
Key exclusion criteria (15 listed)
- Patient receiving a myeloablative conditioning regimen
- Patients receiving allo-HSCT from an haploidentical donor or an umbilical cord blood
- Patients receiving a second or beyond allo-HSCT
- Patient with the underlying hematologic disorder in relapse
- Patients having developed a GVHD before inclusion in the study
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 |
|---|---|---|
| Probe based confocal laser endomicroscopy (Cellvizio)The probe is a miniaturized microscope in the form of a fiber which is inserted through the endoscope and brought into contact with the mucosa. It thus allows for a "live virtual biopsy", that is to say, obtaining real-time microscopic virtual image of the mucosa. It requires an intra-veinous injection of 5 mL of 10% fluorescein diluted in 50 cc of saline serum. The images obtained during the examination will be recorded via the endomicroscopy console so that two endoscopists blinded from the macroscopic and histological findings can review the data. | Device | Probe based confocal laser endomicroscopy (Cellvizio) |
Primary outcome
E-mage Score
Time frame: Once for each patient between day 21 and day 28 after graft
The primary endpoint is the evaluation of E-mage score as a new way to detect the early occurrence of GVH amongst patient undergoing Allo-HSCT, considering its sensibility an sensitivity. The E-mage score will be constructed after an expert committee to define semiquantitative or quantitative criteria allowing the classification of pCLE lesions from no GVH to certain GVH. Those criteria will be set regarding the results of the pilot study. The pCLE images will be interpreted by two endoscopists used to pCLE images and blinded from macroscopic observations. Correlation between the E-mage score calculated for each patient and the gold standard histology will be evaluated and sensibility and specificity of the Emage score will be calculated.
2 secondary outcomes
new early paraclinical markers of GVH and correlation with the occurrence of GVHD
Time frame: up to 3 month after graft
GVHD physiopathology
Time frame: within one year
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 29 Aug 2019.
- Individual participant dataSharing planned: No
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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.
Emmanuel Coron, MD-PHD principal investigator
Nantes University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Probe based confocal laser endomicroscopy (Cellvizio) in people with Graft Versus Host Disease, run by Nantes University Hospital 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 5 inclusion and 15 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 29 Aug 2019. 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?
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?
E-mage Score (time frame: Once for each patient between day 21 and day 28 after graft). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 29 Aug 2019.