Diagnostic Tools for Human African Trypanosomiasis Elimination and Clinical Trials: Early Test-of-cure (DiTECT-WP4)

February 18, 2021 updated by: Institut de Recherche pour le Developpement

Diagnostic Tools for Human African Trypanosomiasis Elimination and Clinical Trials: WP4 Early Test-of-cure

The study validates the diagnostic performance of cerebrospinal fluid neopterin quantification and of blood and cerebrospinal fluid trypanosomal spliced leader RNA detection for assessing outcome after treatment of human African trypanosomiasis.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

In the last decade, the prevalence of Trypanosoma brucei gambiense human African trypanosomiasis (HAT) has fallen and HAT has been targeted for elimination. Development of safe and efficacious drugs for HAT, applicable in an elimination context, is considered as a high priority. The drug developmental process is however slowed down by the need to follow-up treated patients for 18 months to decide on cure. For timely diagnosis of treatment failure in clinical trials, patients should have control visits with follow-up examinations at 6, 12 and 18 months after treatment. Furthermore, due to repeated lumbar punctures, treated patients refrain to present for control visits spontaneously, and tend not to comply with follow-up. Clinical trials on new drugs for HAT would therefore be accelerated by availability of an early test of cure. Trypanosomal spliced leader (SL)-RNA, neopterin & 5-hydroxytryptophan are good candidates for accurate and shortened treatment follow-up. In particular SL-RNA detection in blood offers an opportunity for non-invasive post-treatment follow-up.

The objective of the DiTECT-HAT-WP4 study is to validate the diagnostic performance of cerebrospinal fluid neopterin & 5-hydroxytryptophan quantification and of blood and cerebrospinal fluid trypanosomal spliced leader RNA detection for assessing treatment outcome. The DiTECT-HAT-WP4 study is embedded into an ongoing therapeutic phase II/III study (DNDi-OXA-02-HAT) testing a new oral single dose drug against HAT. Within the Framework of the therapeutical trial, patients will have post-treatment examinations, including blood and cerebrospinal fluid examination at day 11, and during follow-up at month 6, month 12 and month 18. Combination of DiTECT-HAT-WP4 with this ongoing clinical trial allows evaluation of new treatment outcome assessment markers during follow-up without the need for additional lumbar or venipunctures. The volumes of venous blood and cerebrospinal fluid taken will be increased by 2.5 mls for the DiTECT-HAT-WP4 study.

Reverse transcriptase real time PCR for spliced leader RNA detection in blood and cerebrospinal fluid and neopterin detection will be carried out in the reference laboratory in Kinshasa, (index tests). The reference laboratory will be blinded to the results of the reference standard. For evaluation of diagnostic performance of the index tests, the reference standard will consist of classification of treatment outcome according to international standards applied for the clinical trial. Receiver operator curves, sensitivity and specificity of the different index tests for treatment outcome assessment will be determined at each follow-up time point. If sufficiently accurate, trypanosomal spliced leader RNA detection in blood would allow post-treatment follow-up without the need for lumbar punctures. Improved treatment outcome assessment will not only facilitate follow-up by avoiding the feared lumbar puncture but also speed up the development and implementation of new drugs. In addition, it will also improve management of patients in routine. The proposed research will impact on clinical decision and treatment outcomes, and contribute to successful HAT elimination.

Study Type

Interventional

Enrollment (Actual)

88

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

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

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

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Eligible for participation in DNDi-OXA-02-HAT clinical trial

Exclusion Criteria:

  • Excluded for DNDi-OXA-02-HAT clinical trial; No informed consent for participation in the DiTECT-HAT-WP4 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: N/A
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Human african trypanosomiasis patient
RNA, neopterin and 5-hydroxytryptophan detection
Diagnostic test: RNA and neopterin detection
Detection of spliced leader RNA will be performed on blood and cerebrospinal fluid taken before treatment, 11 days after treatment, 6, 12 and 18 months after treatment. Neopterin and 5-hydroxytryptophan will be quantified in cerebrospinal fluid taken at the same time points.
Other Names:
  • Reverse transcriptase real-time PCR Trypanozoon SL-RNA
  • Neopterin & 5-hydroxytryptophan EIA, Mybiosource

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sensitivity of SL-RNA detection in blood, SL-RNA detection in cerebrospinal fluid and of neopterin & 5-hydroxytryptophan quantification in cerebrospinal fluid for relapse after human African trypanosomiasis treatment
Time Frame: 18 months

Index tests: qualitative detection of SL-RNA in blood, qualitative detection of SL-RNA in cerebrospinal fluid, neopterin & 5-hydroxytryptophan quantification in cerebrospinal fluid.

Reference standard: classification according to the WHO 2015 criteria as relapse or probable relapse within 18 months after treatment for human African trypanosomiasis
18 months
Specificity of SL-RNA detection in blood, SL-RNA detection in cerebrospinal fluid and of neopterin & 5-hydroxytryptophan quantification in cerebrospinal fluid for cure after human African trypanosomiasis treatment
Time Frame: 18 months

Index tests: qualitative detection of SL-RNA in blood, qualitative detection of SL-RNA in cerebrospinal fluid, neopterin & 5-hydroxytryptophan quantification in cerebrospinal fluid.

Reference standard: classification according to the WHO 2015 criteria as cure or probable cure 18 months after treatment
18 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sensitivity and specificity SL-RNA detection in blood for outcome assesment after treatment for human African trypanosomiasis
Time Frame: post treatment day 11, month 6, month 12 and month 18

Index tests: qualitative detection of SL-RNA in blood post treatment day 11, month 6, month 12 and month 18.

Reference standard: Human African trypanosomiasis treatment outcome classification according to the WHO 2015 criteria
post treatment day 11, month 6, month 12 and month 18
Sensitivity and specificity SL-RNA detection in cerebrospinal fluid for outcome assesment after treatment for human African trypanosomiasis
Time Frame: post treatment day 11, month 6, month 12 and month 18

Index tests: qualitative detection of SL-RNA in cerebrospinal fluid at post treatment day 11, month 6, month 12 and month 18.

Reference standard: Human African trypanosomiasis treatment outcome classification according to the WHO 2015 criteria
post treatment day 11, month 6, month 12 and month 18
Sensitivity and specificity by ROC analysis of neopterin & 5-hydroxytryptophan quantification in cerebrospinal fluid for outcome assesment after treatment for human African trypanosomiasis
Time Frame: post treatment day 11, month 6, month 12 and month 18

Index tests: quantitative detection of neopterin & 5-hydroxytryptophan in cerebrospinal fluid at post treatment day 11, month 6, month 12 and month 18.

Reference standard: Human African trypanosomiasis treatment outcome classification according to the WHO 2015 criteria
post treatment day 11, month 6, month 12 and month 18

Collaborators and Investigators

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

Sponsor

Institut de Recherche pour le Developpement

Collaborators

Institute of Tropical Medicine, Belgium
Institut National de Recherche Biomédicale. Kinshasa, République Démocratique du Congo
Ministry of Public Health, Democratic Republic of the Congo

Investigators

  • Principal Investigator: Veerle Lejon, PhD, Institut de Recherche pour le Developpement

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

Helpful Links

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 (Actual)

February 24, 2017

Primary Completion (Actual)

January 31, 2021

Study Completion (Actual)

January 31, 2021

Study Registration Dates

First Submitted

March 31, 2017

First Submitted That Met QC Criteria

April 7, 2017

First Posted (Actual)

April 13, 2017

Study Record Updates

Last Update Posted (Actual)

February 21, 2021

Last Update Submitted That Met QC Criteria

February 18, 2021

Last Verified

January 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DiTECT-HAT-WP4

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

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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Locations

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