Candidemia of C. GlabrataCAHOHRNCT03652194
Study of Innate Host Immune Response to C. Glabrata Clinical Isolates Resistant to Echinocandins: Impact on the Management of Candidemia in High-risk Patients
An observational study of Candidemia of C. Glabrata, run by Centre Hospitalier Universitaire Dijon at 1 site in France.
Trial summary
In the context of Candida yeast infections, a large number of studies have been published over the past two decades specifying the molecular mechanisms of antifungal resistance in different Candida species. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Candidemia of C. Glabrata
- What is being tested?
- in vitro evaluation of epithelial immune response during C. glabrata infection and study of the impact of resistance phenotype acquisition on the virulence of C. glabrata isolates
- How many people
- 21 participants
- Where
- 1 siteFrance
- Study dates
- 1 Jan 2018to Jun 2019
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Collection from the "multicentric study of Echinocandin-resistance in Candida glabrata candidemia" (multicentre retrospective study on a cohort of 172 patients managed for a C. glabrata cadidemia between 2013 and 2015).
Who may be able to join
- 10 clinical isolates sensitive to all antifungal agents
- 10 echinocandin-resistant clinical isolates (Eucast, caspofungin > 8µg/ml)
- Clinical strains of C. glabrata susceptible or resistant to echinocandins will be selected on selected criteria:
- patient's immune status
- therapeutic management
- clinical developments
Who cannot join
- Not applicable
Trial locations and contacts
1 site in 1 country.
About this study
In the context of Candida yeast infections, a large number of studies have been published over the past two decades specifying the molecular mechanisms of antifungal resistance in different Candida species. However, few of these studies have explored how these mechanisms influence host immune response to this opportunistic pathogen. Recent advances in understanding how the host's immune system responds to Candida have initiated the emergence of a new research theme aimed at better understanding Candida's intrinsic and adaptive resistance mechanisms to antifungals can modulate "escape to" or "recognition by" the host's immune system. This knowledge could lead to (i) a better understanding of the predominance of certain Candida species with antifungal resistance in certain patient populations, (ii) a better understanding of why high levels of in vitro resistance are not necessarily correlated with in vivo therapeutic failure, and (iii) effective immunotherapeutic strategies to control Candida resistance to antifungals.
It is therefore crucial to investigate the impact of Candida's resistance to antifungals on the host's innate immune response. Indeed, most antifungal resistance mechanisms have a direct or indirect structural modification of the fungal wall. However, it is the composition of this wall that is involved in the recognition of Candida by the host cell via the pattern recognition receptors (PRRs). We therefore put forward the very probable hypothesis that changes in the fungal wall, induced by the appearance of resistance, could alter the recognition of Candida by PRRs and thus trigger a different immune response, either qualitatively (type of cytokines secreted) or quantitatively (amplitude and duration of the immune response). However, even if initial experimental data support the hypothesis of a possible link between resistance and a modulation of the innate immune response in digestive mucosa (the most frequent starting point for disseminated candidiasis), many questions remain regarding (i) the proteins and mechanisms of the modulated immune cascade, (ii) the modification of the immune response according to the Candida species in question and (iii) the modification of the immune response according to the resistance phenotype in question.
- Conditions
- Candidemia of C. Glabrata
- Being tested
- in vitro evaluation of epithelial immune response during C. glabrata infection, study of the impact of resistance phenotype acquisition on the virulence of C. glabrata isolates
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
in vitro evaluation of epithelial immune response during C. glabrata infectionOther
- study of the expression of genes coding for different proteins involved in the RTqPCR activation cascade
- study of protein expression by the Western-Blot method
study of the impact of resistance phenotype acquisition on the virulence of C. glabrata isolatesOther
- in vitro evaluation by measuring cell invasion, cell adhesion and by determining epithelial cell cytotoxicity.
- in vivo evaluation measured by a survival study on a CD-1 mouse model.
| Study group | Role | What they receive |
|---|---|---|
| Reference strain ATCC | 1 strain sensitive to all antifungals Receives: Other: in vitro evaluation of epithelial immune response during C. glabrata infection; Other: study of the impact of resistance phenotype acquisition on the virulence of C. glabrata isolates | |
| Clinical isolates sensitive to all antifungal agents | 10 clinical isolates sensitive to all Receives: Other: in vitro evaluation of epithelial immune response during C. glabrata infection; Other: study of the impact of resistance phenotype acquisition on the virulence of C. glabrata isolates | |
| Echinocandin-resistant clinical isolates | 10 echinocandin-resistant clinical isolates (Eucast, Caspofungin > 8µg/ml) Receives: Other: in vitro evaluation of epithelial immune response during C. glabrata infection; Other: study of the impact of resistance phenotype acquisition on the virulence of C. glabrata isolates |
What is being measured
The primary outcome is the main question the study is designed to answer.
Quantification of accession and invasion
In vitro study of different virulence markers
Measured: Baseline
Test SytoxOrange
In vitro study of different cytotoxicity markers in digestive epithelial cells
Measured: Baseline
Quantification of the gene expression of the various cytokines associated with the immune response in digestive epithelial cells.
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2018
- Study start1 Jan 2018
- Primary completionJan 2019 (estimated)
- Study completionJun 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Candidemia of C. GlabrataStudies of the same condition, open and under way.
- More trials run by Centre Hospitalier Universitaire DijonThe 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
- Other
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Universitaire Dijon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03652194
- Sponsor's protocol ID
- Basmaciyan AOI 2017
- Acronym
- CAHOHR
- Status last verified
- Aug 2018
- First submitted
- 28 Aug 2018
- Last updated
- 29 Aug 2018
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of Innate Host Immune Response to C. Glabrata Clinical Isolates Resistant to Echinocandins: Impact on the Management of Candidemia in High-risk Patients
- ClinicalTrials.gov ID
- NCT03652194
- Acronym / sponsor ID
- CAHOHR / Basmaciyan AOI 2017
- Conditions
- Candidemia of C. Glabrata
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Centre Hospitalier Universitaire DijonUniversity, hospital or other
- Study start
- 1 Jan 2018 (actual)
- Primary completion
- Jan 2019 (estimated)
- Study completion
- Jun 2019 (estimated)
- First posted
- 29 Aug 2018 (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.
In the context of Candida yeast infections, a large number of studies have been published over the past two decades specifying the molecular mechanisms of antifungal resistance in different Candida species. However, few of these studies have explored how these mechanisms influence host immune response to this opportunistic pathogen. Recent advances in understanding how the host's immune system responds to Candida have initiated the emergence of a new research theme aimed at better understanding Candida's intrinsic and adaptive resistance mechanisms to antifungals can modulate "escape to" or "recognition by" the host's immune system. This knowledge could lead to (i) a better understanding of the predominance of certain Candida species with antifungal resistance in certain patient populations, (ii) a better understanding of why high levels of in vitro resistance are not necessarily correlated with in vivo therapeutic failure, and (iii) effective immunotherapeutic strategies to control Candida resistance to antifungals.
It is therefore crucial to investigate the impact of Candida's resistance to antifungals on the host's innate immune response. Indeed, most antifungal resistance mechanisms have a direct or indirect structural modification of the fungal wall. However, it is the composition of this wall that is involved in the recognition of Candida by the host cell via the pattern recognition receptors (PRRs). We therefore put forward the very probable hypothesis that changes in the fungal wall, induced by the appearance of resistance, could alter the recognition of Candida by PRRs and thus trigger a different immune response, either qualitatively (type of cytokines secreted) or quantitatively (amplitude and duration of the immune response). However, even if initial experimental data support the hypothesis of a possible link between resistance and a modulation of the innate immune response in digestive mucosa (the most frequent starting point for disseminated candidiasis), many questions remain regarding (i) the proteins and mechanisms of the modulated immune cascade, (ii) the modification of the immune response according to the Candida species in question and (iii) the modification of the immune response according to the resistance phenotype in question.
Study design
- Observational model
- Cohort
- Time perspective
- Other
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Reference strain ATCC | – | Other: in vitro evaluation of epithelial immune response during C. glabrata infection, Other: study of the impact of resistance phenotype acquisition on the virulence of C. glabrata isolates1 strain sensitive to all antifungals |
| Clinical isolates sensitive to all antifungal agents | – | Other: in vitro evaluation of epithelial immune response during C. glabrata infection, Other: study of the impact of resistance phenotype acquisition on the virulence of C. glabrata isolates10 clinical isolates sensitive to all |
| Echinocandin-resistant clinical isolates | – | Other: in vitro evaluation of epithelial immune response during C. glabrata infection, Other: study of the impact of resistance phenotype acquisition on the virulence of C. glabrata isolates10 echinocandin-resistant clinical isolates (Eucast, Caspofungin > 8µg/ml) |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Collection from the "multicentric study of Echinocandin-resistance in Candida glabrata candidemia" (multicentre retrospective study on a cohort of 172 patients managed for a C. glabrata cadidemia between 2013 and 2015).
Key inclusion criteria (6 listed)
- 10 clinical isolates sensitive to all antifungal agents
- 10 echinocandin-resistant clinical isolates (Eucast, caspofungin > 8µg/ml)
- Clinical strains of C. glabrata susceptible or resistant to echinocandins will be selected on selected criteria:
- patient's immune status
- therapeutic management
Key exclusion criteria (1 listed)
- Not applicable
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 |
|---|---|---|
| in vitro evaluation of epithelial immune response during C. glabrata infection1. study of the expression of genes coding for different proteins involved in the RTqPCR activation cascade 2. study of protein expression by the Western-Blot method | Other | Clinical isolates sensitive to all antifungal agents, Echinocandin-resistant clinical isolates, Reference strain ATCC |
| study of the impact of resistance phenotype acquisition on the virulence of C. glabrata isolates1. in vitro evaluation by measuring cell invasion, cell adhesion and by determining epithelial cell cytotoxicity. 2. in vivo evaluation measured by a survival study on a CD-1 mouse model. | Other | Clinical isolates sensitive to all antifungal agents, Echinocandin-resistant clinical isolates, Reference strain ATCC |
Primary outcome
Quantification of accession and invasion
Time frame: Baseline
In vitro study of different virulence markers
Test SytoxOrange
Time frame: Baseline
In vitro study of different cytotoxicity markers in digestive epithelial cells
Quantification of the gene expression of the various cytokines associated with the immune response in digestive epithelial cells.
Time frame: Baseline
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Aug 2018.
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.
The record lists no contact. Use the official record to reach the sponsor.
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 Candidemia of C. Glabrata, run by Centre Hospitalier Universitaire Dijon 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 6 inclusion and 1 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 29 Aug 2018. 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?
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?
Quantification of accession and invasion (time frame: Baseline). The study lists 3 primary outcomes in all. 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 2018; AzTrials last refreshed its copy on 7 Nov 2026.