Novel Biomarkers for Invasive Aspergillosis

July 2, 2024 updated by: Universitaire Ziekenhuizen KU Leuven
Diagnosis of invasive aspergillosis remains difficult, and is often based on a combination of patient characteristics, radiological and microbiological findings. To data, galactomannan (GM) is the only well-validated biomarker available. However, GM still has its shortcomings. There is therefore a need for new, complementary biomarkers. In this study, two of those tests, bis(methylthio)gliotoxin (bmGT) and a lateral flow device, will be validated in a hematological population, and compare it to GM.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Diagnosis of invasive aspergillosis is often difficult to achieve with certainty, as this requires direct evidence of invasive growth on histopathological examination. A probable diagnosis can be suspected based on both clinical and mycological evidence of the disease, in presence of a susceptible patient. The EORTC-MSG guidelines offer a widely accepted basis for this diagnosis. Under these guidelines, mycological evidence can consist of a positive culture of aspergillus spp, or of detection of galactomannan (GM) in a relevant body sample. GM is a part of the Aspergillus mould and can be detected using a commercially available immunoenzymatic sandwich microplate assay. However, like most biomarkers, galactomannan is far from a perfect biomarker. Several beta-lactam antibiotics are known to cause false positives, and anti-mould therapy has been reported to significantly lower the sensitivity[1]. Additional biomarkers that could circumvent these problems would therefore be beneficial.

A potential new target is gliotoxin (GT), a secondary metabolite of several fungi, the most clinically important of which is Aspergillus[2]. GT is released during invasive growth, and can therefore be used as a biomarker of invasive fungal disease by GT-producing fungi. However, GT is quickly removed by red blood cells from circulation, making it an unreliable marker[3]. A degradation product of GT, bis(methylthio)gliotoxin (bmGT), appears to be more stable as it is not taken up by red blood cells. Serum bmGT or bmGT in bronchoalveolar lavage (BAL) fluid has already been shown in small studies to be a potential marker of invasive aspergillosis, especially when used in combination with GM[3-5].

Recently, another highly specific test has become available, based on detection of an extracellular glycoprotein secreted during the growth of Aspergillus species, using a monoclonal antibody (JF5) in an immunochromatographic lateral-flow device (LFD)[6,7]. This test allows fast (<15 minutes) testing using a commercially available device.

In this study, both the LFD and bmGT will be characterized and validated in a hematological population, and compared to GM.

Study Type

Interventional

Enrollment (Actual)

226

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Leuven, Belgium, 3000
        • University Hospitals Leuven

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

Ages Eligible for Study

16 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age ≥ 16y at start of study
  • One of the following diagnoses:
  • De novo, refractory or relapsed AML/MDS receiving intensive chemotherapy
  • De novo, refractory or relapsed ALL/T-lymphoblastic lymphoma receiving intensive chemotherapy
  • Aplastic anemia requiring ATG therapy
  • Any patient admitted for either autologous or allogeneic hematopoietic stem cell transplantation
  • Written informed consent obtained from the patient

Exclusion Criteria:

  • AML or ALL beyond the specified inclusion criteria
  • Directed treatment for possible, probable, or proven invasive aspergillosis, at moment of screening, or with end of treatment < 6 weeks at screening, or no complete response according to EORTC/MSG criteria, or complete response achieved < 6 weeks at time of screening.

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

  • Primary Purpose: Diagnostic
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Total cohort
Procedure: blood sample
Twice weekly blood sample, and at every outpatient visit

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Diagnostic accuracy of serum bmGT
Time Frame: 2 weeks
Determine the diagnostic accuracy (specificity, sensitivity predictive values, accuracy and other key diagnostic values) of serum bmGT in the diagnosis of invasive aspergillosis, using the revised EORTC criteria as gold standard.
2 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Diagnostic accuracy of a combination of serum bmGT and serum GM
Time Frame: 2 weeks
Determine diagnostic accuracy of a combination of serum GM and serum bmGT in the diagnosis of invasive aspergillosis.
2 weeks
Prognostic value of serum bmGT
Time Frame: 6 weeks
Determine prognostic value (therapy response / mortality) of initial serum bmGT levels.
6 weeks
Prognostic value of serum bmGT kinetics
Time Frame: 6 weeks
Evaluate serum bmGT kinetics as surrogate marker of therapeutic response.
6 weeks
Renal and hepatic influence on bmGT
Time Frame: 2 weeks
Evaluate the impact of renal and hepatic function on initial bmGT levels and bmGT kinetics.
2 weeks
Compare bmGT-HPTLC to bmGT-LC/MS
Time Frame: Same day
Compare bmGT levels as measured by HPTLC to levels as measured by our own in-house developed chromatographic method.
Same day
Diagnostic accuracy of BAL bmGT
Time Frame: 2 weeks
Determine diagnostic accuracy of bmGT in BAL in the diagnosis of invasive aspergillosis.
2 weeks
Diagnostic accuracy of LFD
Time Frame: 2 weeks
Determine diagnostic accuracy of the lateral flow device (LFD) in BAL and serum in the diagnosis of invasive aspergillosis.
2 weeks

Collaborators and Investigators

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

Sponsor

Universitaire Ziekenhuizen KU Leuven

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2017

Primary Completion (Actual)

December 1, 2019

Study Completion (Actual)

February 1, 2020

Study Registration Dates

First Submitted

December 21, 2016

First Submitted That Met QC Criteria

December 21, 2016

First Posted (Estimated)

December 28, 2016

Study Record Updates

Last Update Posted (Actual)

July 3, 2024

Last Update Submitted That Met QC Criteria

July 2, 2024

Last Verified

July 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • S59863

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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