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

NCT03112655 | Completed

• 1 other identifier: DiTECT-HAT-WP4
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 1

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.

Conditions

African Trypanosomiasis; African; Trypanosomiasis, West; Sleeping Sickness; West African; Trypanosoma Brucei Gambiense; Infection

Keywords

diagnosis; sensitivity; specificity; therapeutic outcome; cerebrospinal fluid

Outcome Measures

Primary Outcomes (2)

• 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

  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

  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 Outcomes (3)

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

  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

  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

  post treatment day 11, month 6, month 12 and month 18

Study Arms (1)

Human african trypanosomiasis patient

EXPERIMENTAL

RNA, neopterin and 5-hydroxytryptophan detection

Diagnostic Test: RNA and neopterin detection

Interventions

RNA and neopterin detection DIAGNOSTIC_TEST

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.

Also known as: Reverse transcriptase real-time PCR Trypanozoon SL-RNA, Neopterin & 5-hydroxytryptophan EIA, Mybiosource

Human african trypanosomiasis patient

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Excluded for DNDi-OXA-02-HAT clinical trial; No informed consent for participation in the DiTECT-HAT-WP4 study

Sponsors & Collaborators

• Institut de Recherche pour le Developpement: lead
• Institute of Tropical Medicine, Belgium: collaborator
• Institut National de Recherche Biomédicale. Kinshasa, République Démocratique du Congo: collaborator
• Ministry of Public Health, Democratic Republic of the Congo: collaborator

Study Sites (1)

Programme Nationale de Lutte contre la trypanosomiase humaine Africaine

Kinshasa, Democratic Republic of the Congo

Location

Related Publications (6)

• Gonzalez-Andrade P, Camara M, Ilboudo H, Bucheton B, Jamonneau V, Deborggraeve S. Diagnosis of trypanosomatid infections: targeting the spliced leader RNA. J Mol Diagn. 2014 Jul;16(4):400-4. doi: 10.1016/j.jmoldx.2014.02.006. Epub 2014 May 9.

  PMID: 24814957 BACKGROUND

• Ilboudo H, Camara O, Ravel S, Bucheton B, Lejon V, Camara M, Kabore J, Jamonneau V, Deborggraeve S. Trypanosoma brucei gambiense Spliced Leader RNA Is a More Specific Marker for Cure of Human African Trypanosomiasis Than T. b. gambiense DNA. J Infect Dis. 2015 Dec 15;212(12):1996-8. doi: 10.1093/infdis/jiv337. Epub 2015 Jun 16.

  PMID: 26080371 BACKGROUND

• Tiberti N, Lejon V, Hainard A, Courtioux B, Robin X, Turck N, Kristensson K, Matovu E, Enyaru JC, Mumba Ngoyi D, Krishna S, Bisser S, Ndung'u JM, Buscher P, Sanchez JC. Neopterin is a cerebrospinal fluid marker for treatment outcome evaluation in patients affected by Trypanosoma brucei gambiense sleeping sickness. PLoS Negl Trop Dis. 2013;7(2):e2088. doi: 10.1371/journal.pntd.0002088. Epub 2013 Feb 28.

  PMID: 23469311 BACKGROUND

• Vincent IM, Daly R, Courtioux B, Cattanach AM, Bieler S, Ndung'u JM, Bisser S, Barrett MP. Metabolomics Identifies Multiple Candidate Biomarkers to Diagnose and Stage Human African Trypanosomiasis. PLoS Negl Trop Dis. 2016 Dec 12;10(12):e0005140. doi: 10.1371/journal.pntd.0005140. eCollection 2016 Dec.

  PMID: 27941966 BACKGROUND

• Ngay Lukusa I, Van Reet N, Mumba Ngoyi D, Mwamba Miaka E, Masumu J, Patient Pyana P, Mutombo W, Ngolo D, Kobo V, Akwaso F, Ilunga M, Kaninda L, Mutanda S, Mpoyi Muamba D, Valverde Mordt O, Tarral A, Rembry S, Buscher P, Lejon V. Trypanosome spliced leader RNA for diagnosis of acoziborole treatment outcome in gambiense human African trypanosomiasis: A longitudinal follow-up study. EBioMedicine. 2022 Dec;86:104376. doi: 10.1016/j.ebiom.2022.104376. Epub 2022 Nov 24.

  PMID: 36436279 DERIVED

• Ngay Lukusa I, Van Reet N, Mumba Ngoyi D, Miaka EM, Masumu J, Patient Pyana P, Mutombo W, Ngolo D, Kobo V, Akwaso F, Ilunga M, Kaninda L, Mutanda S, Muamba DM, Valverde Mordt O, Tarral A, Rembry S, Buscher P, Lejon V. Trypanosome SL-RNA detection in blood and cerebrospinal fluid to demonstrate active gambiense human African trypanosomiasis infection. PLoS Negl Trop Dis. 2021 Sep 17;15(9):e0009739. doi: 10.1371/journal.pntd.0009739. eCollection 2021 Sep.

  PMID: 34534223 DERIVED

Related Links

• Human African trypanosomiasis: update of the methodological framework for clinical trials
• phase 1 study of drug now in phase 2/3

MeSH Terms

Conditions

Trypanosomiasis, African; Trypanosomiasis; Infections; Disease; Hypersensitivity

Condition Hierarchy (Ancestors)

Euglenozoa Infections; Protozoan Infections; Parasitic Diseases; Vector Borne Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Immune System Diseases

Study Officials

• Veerle Lejon, PhD

  Institut de Recherche pour le Developpement

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Masking Details: The reference laboratory, generating the results for the index test, is masked for results obtained at the clinical trial site (determining the standard reference).
• Purpose: DIAGNOSTIC
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 31, 2017
• First Posted: April 13, 2017
• Study Start: February 24, 2017
• Primary Completion: January 31, 2021
• Study Completion: January 31, 2021
• Last Updated: February 21, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)