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

Brief Title

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

Official Title

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

Brief Summary

      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.
    

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


Primary Outcome

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

Secondary Outcome

 Sensitivity and specificity SL-RNA detection in blood for outcome assesment after treatment for human African trypanosomiasis

Condition

African Trypanosomiasis

Intervention

RNA and neopterin detection

Study Arms / Comparison Groups

 Human african trypanosomiasis patient
Description:  RNA, neopterin and 5-hydroxytryptophan detection

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Diagnostic Test

Estimated Enrollment

88

Start Date

February 24, 2017

Completion Date

January 31, 2021

Primary Completion Date

January 31, 2021

Eligibility Criteria

        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
      

Gender

All

Ages

15 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Veerle Lejon, PhD, , 

Location Countries

Congo, The Democratic Republic of the

Location Countries

Congo, The Democratic Republic of the

Administrative Informations


NCT ID

NCT03112655

Organization ID

DiTECT-HAT-WP4


Responsible Party

Sponsor

Study Sponsor

Institut de Recherche pour le Developpement

Collaborators

 Institute of Tropical Medicine, Belgium

Study Sponsor

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


Verification Date

January 2021