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Eschar Investigations in Scrub Typhus (EXIST)

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ClinicalTrials.gov Identifier: NCT02915861
Recruitment Status : Recruiting
First Posted : September 27, 2016
Last Update Posted : September 11, 2019
Sponsor:
Collaborator:
Chiangrai Prachanukroh Hospital
Information provided by (Responsible Party):
University of Oxford

Brief Summary:

This is an observational study of patients with scrub typhus (rapid diagnostic test/quantitative polymerase chain reaction (RDT/qPCR) positive) and an inoculation eschar present on examination, recruited from Chiangrai Prachanukroh Hospital, North of Thailand.

In this study, we aim to:

  • Investigate relevant pathogen dissemination dynamics, early innate immune response, and pathogen-host interactions in scrub typhus using a minimal set of easily accessible samples; the inoculation eschar (crust or biopsy), whole blood and - where possible - a lymph node fine-needle aspiration (FNA).
  • Determine the potential use of the inoculation eschar for improving early diagnostics and assessing the diversity of human pathogenic strains; by evaluating non-invasive swabs and scrapings, as well as biopsies for molecular diagnostics templates.
  • Dissect the underlying patho-biology associated with the inoculation eschar and in a subgroup, including the draining lymph node; by defining the spectrum of infected cells via microscopy and double-immune labeling; by determining cytokine and RNA gene expression profiles in blood peripheral blood mononuclear cell (PBMCs) and eschar samples.

Condition or disease Intervention/treatment
Scrub Typhus Other: Non-invasive eschar samples + blood Other: Non-invasive eschar samples+eschar biopsy+blood Other: Non-invasive eschar samples+eschar biopsy+lymph node fine-needle aspiration biopsy+blood Other: Blood+Skin sample

Detailed Description:

Scrub typhus patients will be recruited into the scrub typhus patient (EXP) arm of the study. There will be 3 sub-groups:

  • EXPa (n=12) will have blood and non-invasive eschar samples collected (consent to study, declined biopsy).
  • EXPb (n=12) will have blood, non-invasive eschar samples, and an eschar biopsy collected (consent to study, draining lymph node (LN) inaccessible).
  • EXPc (n=12) will have blood, non-invasive eschar samples, eschar biopsy, and LN FNA collected (consent to study, draining LN accessible).

Samples will be collected at baseline (all) and 2 weeks (blood only).

Control participants will be recruited into the scrub typhus control.

- EXC (n=12) are healthy individuals, attending hospital for elective/minor surgery or treatment of minor skin injury, and normally reside in a scrub typhus endemic region. Blood and a skin sample will be collected at baseline only.


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Study Type : Observational
Estimated Enrollment : 36 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Eschar Investigations to Improve Diagnostics, Understand Early Immune Responses and Characterize Strains for Vaccines in Scrub Typhus
Actual Study Start Date : June 30, 2017
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
EXPa
Scrub typhus patients: Group A
Other: Non-invasive eschar samples + blood
EXPa (n=12) will have blood and non-invasive eschar samples collected (consent to study, declined biopsy).

EXPb
Scrub typhus patients: Group B
Other: Non-invasive eschar samples+eschar biopsy+blood
EXPb (n=12) will have blood, non-invasive eschar samples, and an eschar biopsy collected (consent to study, draining LN inaccessible).

EXPc
Scrub typhus patients: Group C
Other: Non-invasive eschar samples+eschar biopsy+lymph node fine-needle aspiration biopsy+blood
EXPc (n=12) will have blood, non-invasive eschar samples, eschar biopsy, and LN FNA collected (consent to study, draining LN accessible).

EXC
Control group
Other: Blood+Skin sample
Controls (EXC, n=12) are healthy individuals, attending hospital for elective/minor surgery or treatment of minor skin injury, and normally reside in a scrub typhus endemic region. Blood and a skin sample will be collected at baseline only.




Primary Outcome Measures :
  1. Phenotypic characterisation of the major subset of Orientia tsutsugamushi (OT) infected leucocytes within eschar, lymph node, and blood during the dissemination phase of OT in vivo. [ Time Frame: 2 years ]
  2. Characterisation of cytokine and RNA gene expression profiles within the eschar, lymph node, and blood in vivo and comparisons with profiles of uninfected target cells. [ Time Frame: 2 years ]

Secondary Outcome Measures :
  1. Establishing the usefulness of non-invasive eschar samples from patients with acute scrub typhus for diagnostics for OT and for genotyping +/- whole-genome sequencing. [ Time Frame: 2 years ]
  2. Define and contrast the eschar histo-pathological findings in this study in Thailand to previous findings from Laos, where the Gilliam strain predominates. [ Time Frame: 2 years ]
  3. Comparisons to parallel studies in the non-human primate model with emphasis on dissemination dynamics, immunomodulation, and the innate and adaptive immune responses to OT; contributing to vaccine development. [ Time Frame: 2 years ]

Biospecimen Retention:   Samples With DNA
  1. Non-invasive eschar samples
  2. Eschar biopsy
  3. Lymph node fine-needle aspiration biopsy (LN FNA)
  4. Blood


Information from the National Library of Medicine

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Ages Eligible for Study:   7 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

EXP: Male and female patients ≥7 years old with confirmed acute scrub typhus and an eschar present on examination (N=36).

EXC: Healthy individuals ≥7 years old who normally reside in a scrub typhus endemic region, attending hospital for elective/minor surgery or treatment of minor skin injury, and preferably age and sex-matched (N=12).

Criteria

Scrub Typhus Patients (EXP) inclusion criteria:

  • Age ≥7 years old.
  • Presentation to hospital with fever in ≤14 days and a clinical suspicion of typhus.
  • Eschar observed on examination.
  • Scrub typhus RDT positive or OT qPCR positive (if qPCR available at local site by time of study initiation).
  • Willingness to participate in the study. Written informed consent obtained from the patient (≥18 years old) or, written informed assent from participant (≥7 to <18years old) along with written informed consent from participant's parent(s)/legal guardian(s).

Scrub Typhus Controls (EXC) inclusion criteria:

  • Age ≥7 years old.
  • Clinically well, attending elective/minor surgery or for treatment of minor skin injury.
  • Historical diagnosis of scrub typhus (RDT, serology, and/or PCR positivity) more than 2 years ago or living in an endemic area with high risk of previous exposure.
  • Willingness to participate in the study. Written informed consent obtained from the patient (≥18 years old) or written informed assent from participant (≥7 to <18years old) along with written informed consent from participant's parent(s)/legal guardian(s).

Scrub Typhus Patients (EXP) exclusion criteria:

  • Current TB or TB treatment in ≤6 months (contains OT-effective antimicrobials)
  • Documented HIV infection, use of steroids, chemotherapy, other immunosuppressants, or herbal remedies containing steroids, and/or pregnancy

Scrub Typhus Controls (EXC) exclusion criteria:

  • Significant acute intercurrent illness at the time of admission including fever >37.5˚C or infection (including TB) requiring antibiotics
  • Documented HIV infection, use of steroids, chemotherapy, other immunosuppressants, or herbal remedies containing steroids, and/or pregnancy

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): NCT02915861


Contacts
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Contact: Dr. Daniel H. Paris, MD +66-2-203-6373 parigi@tropmedres.ac
Contact: Dr. Tri Wangrangsimakul, MD +66-83-0745931 tri@tropmedres.ac

Locations
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Thailand
Chiangrai Prachanukroh Hospital Recruiting
Chiang Rai, Thailand
Contact: Dr.Tri Wangrangsimakul, MD       tri@tropmedres.ac   
Sponsors and Collaborators
University of Oxford
Chiangrai Prachanukroh Hospital
Investigators
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Principal Investigator: Dr. Tri Wangrangsimakul, MD Chiangrai Prachanukroh Hospital, Chiangrai, Thailand

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Responsible Party: University of Oxford
ClinicalTrials.gov Identifier: NCT02915861     History of Changes
Other Study ID Numbers: MICRO1504
First Posted: September 27, 2016    Key Record Dates
Last Update Posted: September 11, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by University of Oxford:
immune responses
vaccines
Additional relevant MeSH terms:
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Typhus, Epidemic Louse-Borne
Scrub Typhus
Rickettsia Infections
Rickettsiaceae Infections
Gram-Negative Bacterial Infections
Bacterial Infections