Crohn's DiseaseTOPICNCT06244849
TOward a Better Understanding of the autoPhagy Machinery for the Identification of Potential Novel Biomarkers and Therapeutic Targets in Crohn's Disease - TOPIC Study
A study testing Blood samples, Stool simple and Ileocolonic biopsies in people with Crohn's Disease, run by Hospices Civils de Lyon at 2 sites in France.
Trial summary
Crohn's disease (CD) belongs to chronic inflammatory bowel diseases (IBD) affecting over 2 million individuals in the North America and 3.2 million in Europe with an increasing incidence rate in newly industrialized countries experiencing a westernization of lifestyle (1). Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Crohn's Disease
- What is being tested?
- Blood samples, Stool simple and Ileocolonic biopsies
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 170 participants
- Where
- 2 sitesFrance
- Study dates
- 1 Jun 2024to 1 Jan 2026
- 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 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- For patients and non-IBD controls :
- Existing pregnancy, lactation, or intended pregnancy within the next 15 months
- History of disease, including mental/emotional disorder that might interfere with their participation in the study
- Serious secondary illnesses of an acute or chronic nature, which in the opinion of the investigator renders the patient unsuitable for inclusion into the study
- Inability to comply with the protocol requirements
- Presence of an ileo-/colonic stoma
Show all 21Show fewer
- Patients with known colonic stricture and exclusive or predominant anal or perineal Crohn's disease lesions
- Known previous or concurrent malignancy (other than that considered surgically cured, with no evidence for recurrence for 5 years)
- Short bowel syndrome
- Concomitant Clostridium difficile superinfection
- Indeterminate colitis
- Concomitant leukocyte apheresis
- Patients who will be exposed to antibiotics 4 weeks prior the inclusion, given the potential impact on the detection of AIEC colonization in ileal biopsies
- Patients who denied the protocol, not ability to accept or sign consent of the protocol
- Subject involved in another interventional research with an exclusion period still in progress at inclusion
- Pregnant women, women in labor or breastfeeding women*.
- Persons deprived of their liberty by a judicial or administrative decision
- Persons under psychiatric care
- Persons admitted to a health or social institution for purposes other than research
- Adults subject to a legal protection measure (guardianship, curatorship)
- Subject involved in another clinical trial
Trial locations and contacts
2 sites in 1 country.
BOSCHETTI Gilles, Pr contact
France2 sites
CHU Estaing
Clermont-Ferrand, 63000
BUISSON Anthony, Pr, 04 73 75 05 23 ext. +33, a-buisson@hotmail.fr
Centres Hospitalier Lyon Sud
Pierre-Bénite, 69495
NANCEY Stéphane, Pr, 04 78 86 12 89 ext. +33, Stephane.nancey@chu-lyon.fr
About this study
Crohn's disease (CD) belongs to chronic inflammatory bowel diseases (IBD) affecting over 2 million individuals in the North America and 3.2 million in Europe with an increasing incidence rate in newly industrialized countries experiencing a westernization of lifestyle (1). This highly disabling disease affects patients' life in several ways with severe complications requiring surgery for half of them and is responsible for considerable economic burdens (2,3). Decades of research displayed that CD pathogenesis is determined by inappropriate immune responses towards luminal microbiota in genetically susceptible hosts. Genome-wide association studies (GWAS) have identified autophagy as one of the main pathways associated with susceptibility to CD (4-6). Autophagy is a dynamic process of the lysosomal catabolism, called autophagy flux, which is crucial to degrade and recycle obsolete and deleterious cytosolic components of the cell (7). Autophagy is also the main cell-autonomous process to fight intracellular microorganisms by degrading them, and by contributing to antimicrobial host immune responses. However, the functional consequences of polymorphisms affecting autophagy-associated genes on the dynamic process of autophagy and its real impact on CD pathogenesis remain largely unknown. In addition, CD is associated with a gut microbiota dysbiosis, as exemplified by the higher prevalence of AIEC (a bacterium eliminated by autophagy) in ileal mucosa of CD patients (8-10). Hence, autophagy defect, linked to autophagy SNPs, could contribute to CD-related dysbiosis and to CD activity and severity.
Beyond, CD-associated abnormalities of the autophagy flux may affect the composition of the autophagic cargoes, as well as the one of other vesicular pathway, such as exosomes, known to influence autophagy. These impairments could affect at longer term both cell activities and immune responses, especially in antigen presenting cells, which drive host immune responses.
The TOPIC project concerns translational research, in which we plan to generate a prospective cohort of CD patients giving up the unique opportunity to collect clinical data, to analyse simultaneously the autophagy flux, genetic variants of interest (from blood samples) and intestinal microbiota (from intestinal samples) and allowing to perform more fundamental studies. The results of the fundamental part will allow a better understanding of the pathophysiology of CD, and ultimately better management of these patients.
- Conditions
- Crohn's Disease
- Being tested
- Blood samples, Stool simple, Ileocolonic biopsies
- Keywords
- Crohn disease, Autophagy flux, Intestinal microbiota, Biomarker, Non-inflammatory bowel diseases
- Medical subject headings
- Crohn Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood samplesBiological
A 28 mL (5 EDTA tubes of 4 mL and 2 dry tubes) venous blood will be collected added to the standard blood analysis performed in routine
Stool simpleBiological
A fresh stool sample will be collected and conserved at room temperature until shipment
Ileocolonic biopsiesBiological
An ileo-colonoscopy with 10 ileal biopsies scheduled in their regular medical follow-up will be performed
| Study group | Role | What they receive |
|---|---|---|
| Patient with Crohn disease (n=150) | Other | CD patients requiring to undergo an ileo-colonoscopy for routine investigations (assessment of disease activity or complications as stricture or screening of colorectal cancer for CD) Receives: Biological: Blood samples; Biological: Stool simple; Biological: Ileocolonic biopsies |
| Patient without Crohn disease (n=20) | Other | Non-IBD patients (control) requiring to undergo an ileo-colonoscopy for routine investigations (screening for colorectal cancer or diagnosis of irritable bowel syndrome for controls). Receives: Biological: Blood samples; Biological: Stool simple; Biological: Ileocolonic biopsies |
What is being measured
The primary outcome is the main question the study is designed to answer.
Autophagy flux
Difference of the autophagy flux signature according to AIEC infection, autophagy related gene variants, and its relationship between CD activity and severity.
Measured: Baseline and the day of ileocolonoscopy
Secondary outcomes (2)
Characterize and compare the autophagosomal proteome in CD genetic autophagicvariant expressing immune cells in ileum and in colon in CD patients from that in non IBD patients (controls).
Qualitative and/or quantitative comparative analysis of content of the autophagosomal cargos between CD patients expressing the CD-associated autophagy related variants and WT gene-expressing non-IBD controls.
Measured: Baseline and the day of ileocolonoscopy
Characterize and compare the exosomal proteome in CD genetic autophagic variant expressing immune cells in ileum and in colon in CD patients from that in non IBD patients (controls).
Qualitative and/or quantitative comparative analysis of content of the exosomal proteome cargos between CD patients expressing the CD-associated autophagy related variants and WT gene-expressing non-IBD controls.
Measured: Baseline and the day of ileocolonoscopy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2024
- Study start1 Jun 2024 (estimated)
- Primary completion1 Jan 2026 (estimated)
- Study completion1 Jan 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Crohn's DiseaseStudies 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- A case-control study from a prospective bicentric cohort of CD patients. Proof of concept and exploratory study with minimum risks (type 2)
- Masking
- None (open label)
- Enrolment
- 170 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Collaborators
- Centre International de Recherche en Infectiologie (CIRI)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06244849
- Sponsor's protocol ID
- 69HCL22_1172
- Acronym
- TOPIC
- Status last verified
- May 2024
- First submitted
- 14 Dec 2023
- Last updated
- 20 May 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 20 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- TOward a Better Understanding of the autoPhagy Machinery for the Identification of Potential Novel Biomarkers and Therapeutic Targets in Crohn's Disease - TOPIC Study
- ClinicalTrials.gov ID
- NCT06244849
- Acronym / sponsor ID
- TOPIC / 69HCL22_1172
- Conditions
- Crohn's Disease
- Keywords
- Crohn disease, Autophagy flux, Intestinal microbiota, Biomarker, Non-inflammatory bowel diseases
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 170 participants (estimated)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Collaborators
- Centre International de Recherche en Infectiologie (CIRI)
- Study start
- 1 Jun 2024 (estimated)
- Primary completion
- 1 Jan 2026 (estimated)
- Study completion
- 1 Jan 2026 (estimated)
- First posted
- 6 Feb 2024 (actual)
- 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.
Crohn's disease (CD) belongs to chronic inflammatory bowel diseases (IBD) affecting over 2 million individuals in the North America and 3.2 million in Europe with an increasing incidence rate in newly industrialized countries experiencing a westernization of lifestyle (1). This highly disabling disease affects patients' life in several ways with severe complications requiring surgery for half of them and is responsible for considerable economic burdens (2,3). Decades of research displayed that CD pathogenesis is determined by inappropriate immune responses towards luminal microbiota in genetically susceptible hosts. Genome-wide association studies (GWAS) have identified autophagy as one of the main pathways associated with susceptibility to CD (4-6). Autophagy is a dynamic process of the lysosomal catabolism, called autophagy flux, which is crucial to degrade and recycle obsolete and deleterious cytosolic components of the cell (7). Autophagy is also the main cell-autonomous process to fight intracellular microorganisms by degrading them, and by contributing to antimicrobial host immune responses. However, the functional consequences of polymorphisms affecting autophagy-associated genes on the dynamic process of autophagy and its real impact on CD pathogenesis remain largely unknown. In addition, CD is associated with a gut microbiota dysbiosis, as exemplified by the higher prevalence of AIEC (a bacterium eliminated by autophagy) in ileal mucosa of CD patients (8-10). Hence, autophagy defect, linked to autophagy SNPs, could contribute to CD-related dysbiosis and to CD activity and severity.
Beyond, CD-associated abnormalities of the autophagy flux may affect the composition of the autophagic cargoes, as well as the one of other vesicular pathway, such as exosomes, known to influence autophagy. These impairments could affect at longer term both cell activities and immune responses, especially in antigen presenting cells, which drive host immune responses.
The TOPIC project concerns translational research, in which we plan to generate a prospective cohort of CD patients giving up the unique opportunity to collect clinical data, to analyse simultaneously the autophagy flux, genetic variants of interest (from blood samples) and intestinal microbiota (from intestinal samples) and allowing to perform more fundamental studies. The results of the fundamental part will allow a better understanding of the pathophysiology of CD, and ultimately better management of these patients.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- A case-control study from a prospective bicentric cohort of CD patients. Proof of concept and exploratory study with minimum risks (type 2)
| Arm | Type | Receives |
|---|---|---|
| Patient with Crohn disease (n=150) | Other | Biological: Blood samples, Biological: Stool simple, Biological: Ileocolonic biopsiesCD patients requiring to undergo an ileo-colonoscopy for routine investigations (assessment of disease activity or complications as stricture or screening of colorectal cancer for CD) |
| Patient without Crohn disease (n=20) | Other | Biological: Blood samples, Biological: Stool simple, Biological: Ileocolonic biopsiesNon-IBD patients (control) requiring to undergo an ileo-colonoscopy for routine investigations (screening for colorectal cancer or diagnosis of irritable bowel syndrome for controls). |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (21 listed)
- Existing pregnancy, lactation, or intended pregnancy within the next 15 months
- History of disease, including mental/emotional disorder that might interfere with their participation in the study
- Serious secondary illnesses of an acute or chronic nature, which in the opinion of the investigator renders the patient unsuitable for inclusion into the study
- Inability to comply with the protocol requirements
- Presence of an ileo-/colonic stoma
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 |
|---|---|---|
| Blood samplesA 28 mL (5 EDTA tubes of 4 mL and 2 dry tubes) venous blood will be collected added to the standard blood analysis performed in routine | Biological | Patient with Crohn disease (n=150), Patient without Crohn disease (n=20) |
| Stool simpleA fresh stool sample will be collected and conserved at room temperature until shipment | Biological | Patient with Crohn disease (n=150), Patient without Crohn disease (n=20) |
| Ileocolonic biopsiesAn ileo-colonoscopy with 10 ileal biopsies scheduled in their regular medical follow-up will be performed | Biological | Patient with Crohn disease (n=150), Patient without Crohn disease (n=20) |
Primary outcome
Autophagy flux
Time frame: Baseline and the day of ileocolonoscopy
Difference of the autophagy flux signature according to AIEC infection, autophagy related gene variants, and its relationship between CD activity and severity.
2 secondary outcomes
Characterize and compare the autophagosomal proteome in CD genetic autophagicvariant expressing immune cells in ileum and in colon in CD patients from that in non IBD patients (controls).
Time frame: Baseline and the day of ileocolonoscopy
Characterize and compare the exosomal proteome in CD genetic autophagic variant expressing immune cells in ileum and in colon in CD patients from that in non IBD patients (controls).
Time frame: Baseline and the day of ileocolonoscopy
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 May 2024.
- Individual participant dataSharing planned: Undecided
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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.
BOSCHETTI Gilles, Pr contact
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Blood samples, Stool simple and Ileocolonic biopsies in people with Crohn's Disease, run by Hospices Civils de Lyon at 2 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 0 inclusion and 21 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 20 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact NANCEY Stéphane, Pr (0478861289 ext. +33, Stephane.nancey@chu-lyon.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Autophagy flux (time frame: Baseline and the day of ileocolonoscopy). 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 20 May 2024.