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Trial record 54 of 228 for:    yeast

Efflux Pump Mediated Azole Resistance in Candida Albicans

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ClinicalTrials.gov Identifier: NCT03659162
Recruitment Status : Not yet recruiting
First Posted : September 6, 2018
Last Update Posted : September 6, 2018
Sponsor:
Information provided by (Responsible Party):
Sherine Adel, Assiut University

Brief Summary:
Candida albicans is the major fungal pathogen causing infections in humans, ranging from superficial mucosal infection to systemic mycoses. In recent years, Candida infections have increased disproportionately as a result of the increased number of compromised host populations, such as patients with AIDS, diabetes and various cancers, and organ-transplant recipients. Severe oro-pharyngeal candidiasis afflicts many AIDS patients and is a significant infection in cancer patients being treated with chemotherapy and/or radiotherapy.

Condition or disease Intervention/treatment
Fungal Infection Drug: Azole Antifungal

Detailed Description:
In cancer patients, the increased incidence of oro-pharyngeal candidiasis results both from the debilitating effects of the cancer itself and from the immuno-suppressive treatment for the cancer. Administration of broad-spectrum antibiotics for the management of bacterial infections in these patients may further predispose them to oro-pharyngeal candidiasis . Systemic fungal infections are often hard to diagnose, which contributes to their high attributable mortality. In addition, there are far fewer classes of antifungal agent than antibacterial drugs, limiting therapeutic options. The azole antifungals are commonly used to treat fungal infections, as they are conveniently administered and have few side effects . the number of drug-resistant Candida strains has also increased dramatically owing to the increased use of antifungal agents. The major mechanism responsible for high-level azole resistance in clinical Candida isolates is overexpression of plasma membrane efflux pumps . There are two main families of efflux proteins, the ATP-binding cassette pumps and the major facilitator superfamily transporters . Azole resistance calls for the use of alternative antifungal drugs like echinocandins, voriconazole, posaconazole, ravuconazole and Amphotericin B. But constraints like high costs or adverse effects associated with these agents often limit their usage. Some recent pioneering studies have reported the modulating effect of verapamil, oestradiol, progesterone and ibuprofen on resistance of Candida isolates. While fluconazole MIC decreased in most strains after exposure to these modulators, this effect was particularly remarkable for Ibuprofen. The molecular basis of this reversal of resistance has also been demonstrated recently. Thus, drugs capable of reversing fluconazole resistance might offer novel breakthroughs in the treatment of resistant Candida infections. As investigators have previously observed a high prevalence of fluconazole resistance among Candida isolates recovered in our centre. consequently ,implementing the concept of combination therapy using an efflux pump inhibitor seems an adequate strategy for overcoming resistance. in this study investigators were interested in exploring if the resistant phenotype could be reversed in a proportion of these isolates by the use of Ibuprofen .Expression levels of the target genes associated with antifungal resistance of C.albicans (CDR1, CDR2 and MDR1) were assessed by quantitative real-time The relative quantities of the target genes were normalized against ACT1 housekeeping gene expression and analysed using the comparative DDCt method, taking the amplification efficiency into consideration .

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Study Type : Observational
Estimated Enrollment : 100 participants
Observational Model: Other
Time Perspective: Cross-Sectional
Official Title: Efflux Pump Mediated Azole Resistance in Candida Albicans Among Neutropenic Patients With Haematological Malignancies
Estimated Study Start Date : February 17, 2019
Estimated Primary Completion Date : April 10, 2019
Estimated Study Completion Date : July 24, 2019

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
neutropenic cancer patient recieving azoles .
neutropenic cancer patients that undergoing chemotherapy with prophylaxis with azoles and exhibit recurrent fungal infection so appropriate clinical specimen will taken for isolation & identification of causative agent & it's antimicrobial profile then identification of the mechanism of resistance by invitro technique then confirmed by real time pcr.
Drug: Azole Antifungal
oral gel & injections




Primary Outcome Measures :
  1. characterize the clinical Candida albicans strains isolated from neutropenic patients with Hematological Malignancies. [ Time Frame: 3 months ]
    isolation & identification of of Candida albicans by culturing on Sabouraud's Dextrose Agar (SDA) and CHROM Agar Candida then determination of antifungal susceptibility testing by Disk Diffusion test and determination of MIC by broth microdilution method to identify resistant Candida albicans strains to decrease hazard to these high risk group of patients.


Secondary Outcome Measures :
  1. Determination if Ibuprofen could elicit a reversal of fluconazole resistance by interference with efflux pump activity. [ Time Frame: 2month ]
    reverting of resistance to fluconazole using Ibuprofen as efflux pump inhibitor detected by redetermination of MIC values in presence of a subinhibitory concentration of Ibuprofen.

  2. Testing new NS-IDs other than Ibuprofen as efflux pump inhibitor [ Time Frame: 3 months ]
    resistant Candida albicans strains will subject to broth microdilution in presence and absence of other NS-IDs.

  3. Uncover the molecular base of antifungal resistance in C. albicans clinical strains that could be reverted by ibuprofen [ Time Frame: 4 months ]
    quantification of gene expression of genes encoding for efflux pump (CDR1, CDR2 and MDR1) by real time pcrRT-PCR(q RT-PCR) The relative quantities of the target genes were normalized against ACT1 housekeeping gene expression and analysed using the comparative DDCt method, taking the amplification efficiency into consideration.



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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
neutropenic patient with Hematological Malignancy receiving azoles
Criteria

Inclusion Criteria:

  • Patients suffered from neutropenia. Patients with absolute neutrophiles count less than 500 cells / ml . 7 days or more from start of chemotherapy. Also neutropenic patients presented during relapse after first remission of hematological malignancies.

Presence of resistance to at least one azole derivatives.

Exclusion Criteria:

  • Patient who have contraindication to Azoles

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03659162


Contacts
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Contact: . Ehsan Abdelsabor Hassan, Professor 01114478527 dr_ehsan66@yahoo.com
Contact: Michael Nazmy Agban, Assistant Professor 01223961695 agbanmichael@aun.edu.eg

Sponsors and Collaborators
Assiut University

Publications:

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Responsible Party: Sherine Adel, Principle Investigator, Assiut University
ClinicalTrials.gov Identifier: NCT03659162     History of Changes
Other Study ID Numbers: xoxo
First Posted: September 6, 2018    Key Record Dates
Last Update Posted: September 6, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Mycoses
Antifungal Agents
Miconazole
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP2C9 Inhibitors
Cytochrome P-450 CYP3A Inhibitors