Hepatosplenic CANdidiasis : PETscan and Immune Response Analysis

Neutropenia Clinical Trial

— CANHPARI  

Official title:

Multicenter Prospective Pilot Study Investigating Pathophysiology, Diagnostic and Therapeutic Strategies of Hepatosplenic Candidiasis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01916057
• Other study ID #: P120115
• Secondary ID: AOM12047
• Status: Completed
• Phase: N/A
• Start date: November 19, 2013
• Est. completion date: February 28, 2018

Study information

• Verified date: April 2018
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether F18 fluorodeoxyglucose (18F-FDG) positron-emission tomography scan (PET scan) is useful for the therapy strategy of hepatosplenic candidiasis.

Description:

Chronic disseminated candidiasis, often referred to as hepatosplenic candidiasis (HSC), is an infection due to Candida spp. that mainly involves the liver and spleen. HSC occurs mostly in patients with profound and prolonged neutropenia, which is more often seen in patients with hematologic malignancies. Despite an appropriate antifungal prophylaxis, the incidence of HSC in France might be closed to 5% in patients suffering from acute leukemia. Early and adequate diagnosis and treatment of HSC are crucial, as treatment delays can negatively affect the prognosis of the underlying condition. Current guidelines recommend a 6-month duration treatment. Prolonged treatments up to 6 months are frequent, leading to antifungal toxicity and cost increase. Preliminary study by our team has already assessed F18 fluorodeoxyglucose (18F-FDG) positron-emission tomography scan (PET scan) as a diagnostic tool for HSC. 18F-FDG PET scan could be helpful in the diagnosis, follow-up and therapy strategy of HSC, helping to stop antifungal treatment. Other molecular, immunological and serological tools have to be developed in order to avoid hepatic biopsies. Actually, mycological evidence of infection is found in only 20% of the cases. The pathogenesis of HSC is also not well understood, but it is believed that it may be due to an unbalanced adaptive immune response that leads to an exacerbated inflammatory reaction, resulting in an Immune Reconstitution Inflammatory Syndrome (IRIS). In that context, a better understanding of the disease pathophysiology and of the potential genetic susceptibility could have an impact on therapy strategy. For example, new approaches such as the use of adjuvant high-dose corticosteroids have been shown beneficial. This study is the first step to improve HSC diagnosis and therapy strategy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: February 28, 2018
• Est. primary completion date: June 1, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Patients' inclusion criteria:

• Adults aged =18 years-old

• Hospitalized for hematological malignancy or hematopoietic stem cell transplantation

• Recent (>2months), prolonged (>10 days), profound (>100 PMN/mm3), feverish neutropenia

• Suspected hepatosplenic candidiasis (typical small nodular lesions on abdominal RMI or CT)

Patients' exclusion criteria:

• hepatosplenic lesions of other proven origin

Patients' non-inclusion criteria:

• Life expectancy >3 months

• Pregnancy

• HIV infection

• Hepatic biopsy within 3 weeks before 18F-FDG PET scan

Related Conditions & MeSH terms

• Candidiasis
• Chronic Disseminated Candidiasis
• Hematological Malignancies
• Hematopoietic Stem Cell Transplantation
• Invasive Fungal Disease
• Invasive Fungal Infections
• Mycoses
• Neutropenia

Intervention

Device:
• 18F-FDG PET Scan
to determine whether F18 fluorodeoxyglucose (18F-FDG) positron-emission tomography scan (PET scan) is useful for the therapy strategy of hepatosplenic candidiasis.

Locations

Country	Name	City	State
France	Service des Maladies Infectieuses et Tropicales - Centre d'Infectiologie Necker-Pasteur, IHU Imagine - Hôpital Necker-Enfants Malades,	Paris

Sponsors (5)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	Institut National de la Santé Et de la Recherche Médicale, France, Institut Pasteur, University Hospital, Lille, University of Lausanne Hospitals

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Global response to therapy	Clinical assessment (no fever) and PET scan assessment (intensity of liver and/or spleen lesions)	at month 3
Secondary	18F-FDG PET scan and RMI usefulness in initial diagnosis	Comparison between Day 0 and Month 3 exams	at month 3
Secondary	Serological and molecular mycological tools assessment	Measurement of beta-1,3-D-glucans, mannan/anti-mannan, anti-Saccharomyces cerevisiae antibodies in comparison with controls.; Assessment of a new real-time PCR on serum and hepatic tissue	at day 0
Secondary	Serological and molecular mycological tools assessment	Measurement of beta-1,3-D-glucans, mannan/anti-mannan, anti-Saccharomyces cerevisiae antibodies in comparison with controls.; Assessment of a new real-time PCR on serum and hepatic tissue	at Month 3
Secondary	Serological and molecular mycological tools assessment	Measurement of beta-1,3-D-glucans, mannan/anti-mannan, anti-Saccharomyces cerevisiae antibodies in comparison with controls.; Assessment of a new real-time PCR on serum and hepatic tissue	at Month 6
Secondary	Inflammatory cells and mediators	Measurement of cytokines and lymphocytes populations on serum and hepatic tissue in comparison with controls	at day 0
Secondary	Inflammatory cells and mediators	Measurement of cytokines and lymphocytes populations on serum and hepatic tissue in comparison with controls	at month 3
Secondary	Inflammatory cells and mediators	Measurement of cytokines and lymphocytes populations on serum and hepatic tissue in comparison with controls	at month 6
Secondary	Genetic susceptibility	Search for susceptibility genes to candidiasis in comparison with controls	at day 0