Scrub TyphusEXISTNCT02915861
Eschar Investigations in Scrub Typhus
An observational study of Scrub Typhus, run by University of Oxford at 1 site in Thailand.
Trial 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. Read more about this study
- Who is it for?
- Ages 7 years and older
- Conditions the study is for
- Scrub Typhus
- What is being tested?
- Non-invasive eschar samples + blood, Non-invasive eschar samples+eschar biopsy+blood and Non-invasive eschar samples+eschar biopsy+lymph node fine-needle aspiration biopsy+blood
- How many people
- 44 participants
- Where
- 1 siteThailand
- Study dates
- 30 Jun 2017to 31 May 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 7 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
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).
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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Eschar Investigations to Improve Diagnostics, Understand Early Immune Responses and Characterize Strains for Vaccines in Scrub Typhus
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:
Read more
- 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.
Data sharing:
No future analysis or study of legacy data/specimens including data sharing for purposes not specified in the protocol will be done without seeking further regulatory (EC/IRB) approval
- Any requests for data sharing will be considered by MORU's data sharing committee
- Any data subsequently shared will be anonymised and will not include personal identifiers
Read the 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.
- Conditions
- Scrub Typhus
- Being tested
- Non-invasive eschar samples + blood, Non-invasive eschar samples+eschar biopsy+blood, Non-invasive eschar samples+eschar biopsy+lymph node fine-needle aspiration biopsy+blood, Blood+Skin sample
- Keywords
- immune responses, vaccines
- Medical subject headings
- Scrub Typhus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Non-invasive eschar samples + bloodOther
EXPa (n=12) will have blood and non-invasive eschar samples collected (consent to study, declined biopsy).
Non-invasive eschar samples+eschar biopsy+bloodOther
EXPb (n=12) will have blood, non-invasive eschar samples, and an eschar biopsy collected (consent to study, draining LN inaccessible).
Non-invasive eschar samples+eschar biopsy+lymph node fine-needle aspiration biopsy+bloodOther
EXPc (n=12) will have blood, non-invasive eschar samples, eschar biopsy, and LN FNA collected (consent to study, draining LN accessible).
Blood+Skin sampleOther
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.
| Study group | Role | What they receive |
|---|---|---|
| EXPa | Scrub typhus patients: Group A Receives: Other: Non-invasive eschar samples + blood | |
| EXPb | Scrub typhus patients: Group B Receives: Other: Non-invasive eschar samples+eschar biopsy+blood | |
| EXPc | Scrub typhus patients: Group C Receives: Other: Non-invasive eschar samples+eschar biopsy+lymph node fine-needle aspiration biopsy+blood | |
| EXC | Control group Receives: Other: Blood+Skin sample |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 2 years
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.
Measured: 2 years
Secondary outcomes (3)
Establishing the usefulness of non-invasive eschar samples from patients with acute scrub typhus for diagnostics for OT and for genotyping +/- whole-genome sequencing.
Measured: 2 years
Define and contrast the eschar histo-pathological findings in this study in Thailand to previous findings from Laos, where the Gilliam strain predominates.
Measured: 2 years
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.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Sep 2016 (estimated)
- Study start30 Jun 2017
- Primary completion31 May 2021
- Study completion31 May 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Scrub TyphusStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- Chiangrai Prachanukroh Hospital
- Responsible party
- Sponsor
- Investigators
- Dr. Tri Wangrangsimakul, MD, Principal investigator, Chiangrai Prachanukroh Hospital, Chiangrai, Thailand
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02915861
- Sponsor's protocol ID
- MICRO1504
- Acronym
- EXIST
- Status last verified
- Jul 2021
- First submitted
- 22 Sep 2016
- Last updated
- 5 Aug 2021
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Eschar Investigations to Improve Diagnostics, Understand Early Immune Responses and Characterize Strains for Vaccines in Scrub Typhus
- ClinicalTrials.gov ID
- NCT02915861
- Acronym / sponsor ID
- EXIST / MICRO1504
- Conditions
- Scrub Typhus
- Keywords
- immune responses, vaccines
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- Chiangrai Prachanukroh Hospital
- Study start
- 30 Jun 2017 (actual)
- Primary completion
- 31 May 2021 (actual)
- Study completion
- 31 May 2021 (actual)
- First posted
- 27 Sep 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Data sharing:
No future analysis or study of legacy data/specimens including data sharing for purposes not specified in the protocol will be done without seeking further regulatory (EC/IRB) approval
- Any requests for data sharing will be considered by MORU's data sharing committee
- Any data subsequently shared will be anonymised and will not include personal identifiers
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.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| EXPa | – | Other: Non-invasive eschar samples + bloodScrub typhus patients: Group A |
| EXPb | – | Other: Non-invasive eschar samples+eschar biopsy+bloodScrub typhus patients: Group B |
| EXPc | – | Other: Non-invasive eschar samples+eschar biopsy+lymph node fine-needle aspiration biopsy+bloodScrub typhus patients: Group C |
| EXC | – | Other: Blood+Skin sampleControl group |
Who may qualify
- Ages
- 7 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Non-invasive eschar samples + bloodEXPa (n=12) will have blood and non-invasive eschar samples collected (consent to study, declined biopsy). | Other | EXPa |
| Non-invasive eschar samples+eschar biopsy+bloodEXPb (n=12) will have blood, non-invasive eschar samples, and an eschar biopsy collected (consent to study, draining LN inaccessible). | Other | EXPb |
| Non-invasive eschar samples+eschar biopsy+lymph node fine-needle aspiration biopsy+bloodEXPc (n=12) will have blood, non-invasive eschar samples, eschar biopsy, and LN FNA collected (consent to study, draining LN accessible). | Other | EXPc |
| Blood+Skin sampleControls (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. | Other | EXC |
Primary outcome
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
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
3 secondary outcomes
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
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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Aug 2021.
- Individual participant dataSharing planned: No
Related trials for Scrub Typhus
RecruitingPhase 2/3
Rickettsia Clearance Study
Infectious Disease, Therapeutics
Active, not recruitingPhase 4
Scrub Typhus Antibiotic Resistance Trial
Scrub Typhus
Active, not recruitingObservational study
Scrub Typhus Infection Induced Cardiovascular Disease
Scrub Typhus, Cardiovascular Complication
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dr. Tri Wangrangsimakul, MD principal investigator
Chiangrai Prachanukroh Hospital, Chiangrai, Thailand
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Scrub Typhus, run by University of Oxford at 1 site in Thailand.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Thailand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Aug 2021.