Determination of New Detection and Quantification Thresholds for Serological and Molecular Tests for Hepatitis Delta Virus (HDV) Using Capillary Blood on Blotting Paper (DBS) (SACADE)

October 17, 2024 updated by: Institut de Médecine et d'Epidémiologie Appliquée - Fondation Internationale Léon M'Ba

The Delta hepatitis virus (HDV) is a satellite virus that requires the presence of hepatitis B virus (HBV) for infection. Approximately 5% of HBV-infected individuals, or about 12 million people globally, are also carriers of HDV. This dual infection significantly heightens the risk of liver damage and the progression to hepatocellular carcinoma (HCC).

Historically, the diagnosis of HDV has been limited, leading to an underestimation of its true prevalence both nationally and internationally. Recent advancements in treatments for viral hepatitis and the introduction of new HDV-specific therapies have spurred increased interest in the virus, prompting public health authorities to call for improved diagnostic and monitoring tools.

Detection of HDV typically involves serological tests (ELISA/CLIA) on serum or plasma, followed by viral load quantification using RT-qPCR if positive. However, laboratory access is often insufficient in many regions, particularly affecting marginalized populations and high-endemic areas, especially in low-resource countries. New sample collection methods that help connect patients to expert laboratories are needed, as shipping frozen biological samples can be complex and costly.

In response, Dried Blood Spot (DBS) sampling-where serum, plasma, or whole blood is dried on filter paper-has been adopted by numerous public health organizations as a simple, cost-effective, and non-infectious means of storage and transport. DBS is already validated for diagnosing and monitoring infections such as HIV, HBV, and HCV.

Given the unique biology of each virus, specific studies are required to determine how using DBS affects detection and quantification thresholds for each laboratory technique. The National Reference Center for Delta Hepatitis (CNR-Delta), commissioned by Public Health France, has developed a DBS protocol for HDV, based on available literature and prior studies regarding storage conditions and reconstitution solutions. Two retrospective studies utilizing CNR collections have established new positivity thresholds for serology and detection/quantification in molecular biology for serum/plasma and EDTA whole blood on DBS.

To finalize this protocol, further study of thresholds for capillary blood tests on DBS is essential. Capillary blood, obtained via finger prick, could simplify the use of this tool, reducing the need for specialised equipment and expertise, and potentially allowing for self-sampling by patients.

The current study aims to validate the DBS tool for HDV serological and molecular testing using capillary blood. The hypothesis posits that geographical barriers to accessing hospitals and laboratories for HDV patients complicate the shipping of frozen plasma samples, increasing costs. Developing a serological screening and viral load testing technique from a drop of capillary blood on DBS paper could effectively link patients to specialized centers. Since DBS is considered non-infectious, it also mitigates administrative complications.

By comparing results from paired samples-plasma (the gold standard) from EDTA whole blood and capillary blood on DBS-we aim to redefine detection and quantification thresholds for both methods. Validating these new thresholds will allow the use of this tool while maintaining quality standards for diagnosing and monitoring active HDV infections.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

The Delta hepatitis virus (HDV) is a satellite virus that requires the presence of hepatitis B virus (HBV) for infection. Approximately 5% of HBV-infected individuals, or about 12 million people globally, are also carriers of HDV. This dual infection significantly heightens the risk of liver damage and the progression to hepatocellular carcinoma (HCC).

Historically, the diagnosis of HDV has been limited, leading to an underestimation of its true prevalence both nationally and internationally. Recent advancements in treatments for viral hepatitis and the introduction of new HDV-specific therapies have spurred increased interest in the virus, prompting public health authorities to call for improved diagnostic and monitoring tools.

Detection of HDV typically involves serological tests (ELISA/CLIA) on serum or plasma, followed by viral load quantification using RT-qPCR if positive. However, laboratory access is often insufficient in many regions, particularly affecting marginalized populations and high-endemic areas, especially in low-resource countries. New sample collection methods that help connect patients to expert laboratories are needed, as shipping frozen biological samples can be complex and costly.

In response, Dried Blood Spot (DBS) sampling-where serum, plasma, or whole blood is dried on filter paper-has been adopted by numerous public health organizations as a simple, cost-effective, and non-infectious means of storage and transport. DBS is already validated for diagnosing and monitoring infections such as HIV, HBV, and HCV.

Given the unique biology of each virus, specific studies are required to determine how using DBS affects detection and quantification thresholds for each laboratory technique. The National Reference Center for Delta Hepatitis (CNR-Delta), commissioned by Public Health France, has developed a DBS protocol for HDV, based on available literature and prior studies regarding storage conditions and reconstitution solutions. Two retrospective studies utilizing CNR collections have established new positivity thresholds for serology and detection/quantification in molecular biology for serum/plasma and EDTA whole blood on DBS.

To finalize this protocol, further study of thresholds for capillary blood tests on DBS is essential. Capillary blood, obtained via finger prick, could simplify the use of this tool, reducing the need for specialised equipment and expertise, and potentially allowing for self-sampling by patients.

The current study aims to validate the DBS tool for HDV serological and molecular testing using capillary blood. The hypothesis posits that geographical barriers to accessing hospitals and laboratories for HDV patients complicate the shipping of frozen plasma samples, increasing costs. Developing a serological screening and viral load testing technique from a drop of capillary blood on DBS paper could effectively link patients to specialized centers. Since DBS is considered non-infectious, it also mitigates administrative complications.

By comparing results from paired samples-plasma (the gold standard) from EDTA whole blood and capillary blood on DBS-we aim to redefine detection and quantification thresholds for both methods. Validating these new thresholds will allow the use of this tool while maintaining quality standards for diagnosing and monitoring active HDV infections.

The benefits of the capillary blood on DBS protocol include:

  • For patients: Improved access to care regardless of geographic location and easier sampling (self-sampling).
  • For clinicians: Simplified management and extended screening to hard-to-reach populations.
  • For laboratories: Reduced transportation costs and infectious risk.
  • For the CNR: The opportunity to study global prevalence with a simplified protocol.

In summary, the "gold standard" for diagnosing and monitoring HDV infection involves serology on serum or plasma, testing for total anti-HDV antibodies followed by viral load quantification. To assess whether tests from dried capillary blood can replace plasma/serum tests, a comparative study is necessary, where plasma samples and a drop of capillary blood are collected simultaneously from the same patient and tested in parallel. This comparison will evaluate the sensitivity and specificity of the DBS tool using capillary blood and establish new detection and quantification thresholds for viral load on DBS.

Study Type

Interventional

Enrollment (Estimated)

120

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 Contact

Study Contact Backup

Study Locations

  • France
      • Bobigny, France, 93100
        • Centre National de Référence associé de l'Hépatite Delta (CNR-Delta)
        • Principal Investigator:
          • Tarik Asselah
        • Principal Investigator:
          • Vincent LEROY
        • Principal Investigator:
          • Julie Chas
        • Principal Investigator:
          • Violaine Ozenne
        • Contact:
        • Principal Investigator:
          • Véronique Grando
        • Principal Investigator:
          • Anaïs Vallet-Pichard
        • Principal Investigator:
          • Bruno Roche
        • Principal Investigator:
          • Jessica Coelho

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Adult patients (18 years old and above)
  • Patient infected by the Hepatitis Delta Virus (HDV positive serology)
  • Patient followed by one of the participating APHP hospitals' hepatology department
  • Patient for whom peripheral blood sampling is already planned as part of their medical follow-up.
  • Free, informed and signed consent.

Exclusion Criteria:

  • Patient without blood sampling scheduled as part of medical follow-up.
  • Patient with a condition that makes fingertip capillary puncture impossible.
  • Patient refusing to participate in the study

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: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Capillary Blood on DBS
A total of 100µL of capillary blood will be deposited onto DBS
Diagnostic test: Dried Blood Spot
Comparing analysis results between dried blood spot and plasma
Experimental: Plasma from EDTA whole blood
Plasma from peripheral blood
Diagnostic test: Analysis on plasma
Analysis on plasma

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
HDV serology
Time Frame: At enrollment
Comparison between total anti-HDV antibody detection results on Diasorin Liaison XL on plasma obtained from peripheral blood (EDTA) and on capillary blood blotted onto filter paper.
At enrollment
HDV viral load
Time Frame: At enrollment
Comparison between HDV viral load results obtained by RT-qPCR (Eurobioplex EBX-071) on plasma from peripheral blood (EDTA) and capillary blotted onto filter paper.
At enrollment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Genotyping
Time Frame: At enrollment
Comparison between R0 RNA sequences (SANGER) on plasma obtained from peripheral blood (EDTA) and capillary blood blotted onto filter paper.
At enrollment

Collaborators and Investigators

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

Sponsor

Institut de Médecine et d'Epidémiologie Appliquée - Fondation Internationale Léon M'Ba

Collaborators

CNR Hepatite Delta

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 (Estimated)

November 30, 2024

Primary Completion (Estimated)

December 1, 2025

Study Completion (Estimated)

July 1, 2026

Study Registration Dates

First Submitted

October 17, 2024

First Submitted That Met QC Criteria

October 17, 2024

First Posted (Actual)

October 18, 2024

Study Record Updates

Last Update Posted (Actual)

October 18, 2024

Last Update Submitted That Met QC Criteria

October 17, 2024

Last Verified

October 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IMEA

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

All data will anonymous

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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