Clinical trial NCT06624501: Integrated Discovery and Development of Innovative TB Diagnostics
Official title: Integrated Discovery and Development of Innovative TB Diagnostics
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Tuberculosis, Pulmonary
Keywords: pediatric
diagnostic
cell-free DNA
molecular
tuberculosis
Lead sponsor: Harvard University Faculty of Medicine
Sponsor class: OTHER
First posted: 2024-10-03
Enrollment: 1450
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population will comprise (1) children (0-14 years) with symptoms of tuberculosis disease (TB) and (2) adults \>18 years of age with a diagnosis TB. All participants will be recruited from Lima, Peru.

Brief summary: The long term goal of this project is to provide information critical to the development and use of a low-cost, point-of-care, rapid, simple, and highly accurate diagnostic tool that can help clinicians make a microbiological diagnosis in children who present with signs and symptoms suggestive of TB.

Specific aim 1: To identify the types of patient samples from which to best detect Mtb DNA in children with TB. We propose to obtain serial samples of sputum, blood, stool, and gastric and nasopharyngeal secretions from children with symptomatic TB and to use molecular methods to characterize the distribution of Mtb in these samples. The results of this study will allow us to identify the most promising sampling strategies for diagnosis of TB in children so that optimization of these easily-accessible samples for detection of Mtb nucleic acids can be addressed.

Specific aim 2: To determine whether cell free Mtb DNA can be detected in plasma and urine samples of children and adults with TB and to describe the host-related factors that alter the sensitivity of this assay. We propose to test serial urine and plasma samples for Mtb DNA fragments in two groups: (1) children with symptoms of TB and (2) adults with TB. Here, we will optimize sample volume sizes and of state-of-the-art sequencing tools to improve DNA recovery and detection. This study will help identify optimal samples and strategies for the non-invasive diagnosis of Mtb using urine.

Secondary aim: To create a bank of archived specimens for (1) optimization of Mtb DNA purification, extraction, and (2) use in future pediatric TB diagnostic research.


Eligibility criteria: Inclusion Criteria for aim 1:

Children must meet all of the following criteria at the time of enrollment to participate:

* Age \< 15 years;
* Presents to a participating health center;
* Meets the Criteria for Enrollment of Children Into TB Diagnostic Evaluation Studies
* Has a history of contact with an adult with TB disease; and
* A guardian provides informed consent for minor to participate and, if age 8 to 14 years, the minor also provides assent.

Inclusion criteria for aim 2:

Inclusion criteria for children who participate in Aim 2 will be the same as for those for Aim 1. Adults who participate in Aim 2 must meet all of the following criteria at the time of enrollment to participate.

* Age ≥ 18 years;
* Presents to a participating health center;
* Is diagnosed with incident pulmonary TB;
* Has sputum smear microscopy results;
* Has not yet initiated tuberculosis treatment; and
* Is willing to receive a rapid HIV test.

Exclusion Criteria:

-

Primary outcomes:
measure: Sensitivity for detection of Mtb, by sample type
timeFrame: Baseline
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Harvard Medical School (HMS and HSDM)
name: Molly F. Franke, ScD
role: PRINCIPAL_INVESTIGATOR
References: