Candidemia of C. Glabrata Clinical Trial
— CAHOHROfficial 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
| Verified date | August 2018 |
| Source | Centre Hospitalier Universitaire Dijon |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Observational |
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.
| Status | Active, not recruiting |
| Enrollment | 21 |
| Est. completion date | June 2019 |
| Est. primary completion date | January 2019 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | N/A and older |
| Eligibility |
Inclusion Criteria: - 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 Exclusion Criteria: |
| Country | Name | City | State |
|---|---|---|---|
| France | Chu Dijon Bourogne | Dijon |
| Lead Sponsor | Collaborator |
|---|---|
| Centre Hospitalier Universitaire Dijon |
France,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Quantification of accession and invasion | In vitro study of different virulence markers | Baseline | |
| Primary | Test SytoxOrange | In vitro study of different cytotoxicity markers in digestive epithelial cells | Baseline | |
| Primary | Quantification of the gene expression of the various cytokines associated with the immune response in digestive epithelial cells. | Baseline |