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Trial record 3 of 3 for:    DiTECT-HAT

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

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ClinicalTrials.gov Identifier: NCT03112655
Recruitment Status : Completed
First Posted : April 13, 2017
Last Update Posted : February 21, 2021
Sponsor:
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
Information provided by (Responsible Party):
Institut de Recherche pour le Developpement

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.

Condition or disease Intervention/treatment Phase
African Trypanosomiasis African; Trypanosomiasis, West Sleeping Sickness; West African Trypanosoma Brucei Gambiense; Infection Diagnostic Test: RNA and neopterin detection Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 88 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Masking Description: The reference laboratory, generating the results for the index test, is masked for results obtained at the clinical trial site (determining the standard reference).
Primary Purpose: Diagnostic
Official Title: Diagnostic Tools for Human African Trypanosomiasis Elimination and Clinical Trials: WP4 Early Test-of-cure
Actual Study Start Date : February 24, 2017
Actual Primary Completion Date : January 31, 2021
Actual Study Completion Date : January 31, 2021


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




Primary Outcome Measures :
  1. 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


  2. 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



Secondary Outcome Measures :
  1. 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


  2. 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


  3. 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




Information from the National Library of Medicine

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Ages Eligible for Study:   15 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03112655


Locations
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Congo, The Democratic Republic of the
Programme Nationale de Lutte contre la trypanosomiase humaine Africaine
Kinshasa, Congo, The Democratic Republic of the
Sponsors and Collaborators
Institut de Recherche pour le Developpement
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
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Principal Investigator: Veerle Lejon, PhD Institut de Recherche pour le Developpement
Additional Information:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Institut de Recherche pour le Developpement
ClinicalTrials.gov Identifier: NCT03112655    
Other Study ID Numbers: DiTECT-HAT-WP4
First Posted: April 13, 2017    Key Record Dates
Last Update Posted: February 21, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Institut de Recherche pour le Developpement:
diagnosis
sensitivity
specificity
therapeutic outcome
cerebrospinal fluid
Additional relevant MeSH terms:
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Trypanosomiasis
Trypanosomiasis, African
Euglenozoa Infections
Protozoan Infections
Parasitic Diseases
Infections
Vector Borne Diseases
5-Hydroxytryptophan
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs