Efflux Pump Mediated Azole Resistance in Candida Albicans

September 2, 2018 updated by: Sherine Adel, Assiut University

Efflux Pump Mediated Azole Resistance in Candida Albicans Among Neutropenic Patients With Haematological Malignancies

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

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Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 .

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
100

Contacts and Locations

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Study Contact

Study Contact

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Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

neutropenic patient with Hematological Malignancy receiving azoles

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Other
  • Time Perspectives: Cross-Sectional

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
3 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
2month
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 months
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.
4 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Assiut University

Publications and helpful links

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General Publications

Study record dates

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Study Major Dates

Study Start (Anticipated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 17, 2019

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 10, 2019

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 24, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 31, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 2, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 6, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 6, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 2, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • xoxo

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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