Integrated Discovery and Development of Innovative TB Diagnostics

NCT06624501 | Completed

• 1 other identifier: 5U19AI109755-04
• Study Type: observational
• Target: 1,450
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Tuberculosis, Pulmonary

Keywords

pediatric; diagnostic; cell-free DNA; molecular; tuberculosis

Outcome Measures

Primary Outcomes (1)

• Sensitivity for detection of Mtb, by sample type

  For each type of biologic specimen, the proportion of samples in which Mtb could be isolated by DNA detection methods (sensitivity) relative to the standard of care (a combination of sputum smear, sputum culture, signs and symptoms).

  Baseline

Study Arms (1)

Children and adults

Children with symptoms of TB and adults with smear-positive or smear-negative pulmonary TB.

Other: Observational cohort study

Interventions

Observational cohort study OTHER

Children and adults

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Harvard University Faculty of Medicine: lead

Biospecimen

Retention: SAMPLES WITH DNA

The study maintains a biobank of 9 different sample types collected from children and adults, including: nasopharyngeal swabs, oral swabs, urine, stool, gastric aspirates, sputum, plasma and whole blood.

MeSH Terms

Conditions

Tuberculosis, Pulmonary; Disease; Tuberculosis

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Molly F. Franke, ScD

  Harvard Medical School (HMS and HSDM)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Global Health and Social Medicine

Study Record Dates

• First Submitted: March 5, 2019
• First Posted: October 3, 2024
• Study Start: May 1, 2015
• Primary Completion: February 28, 2018
• Study Completion: February 28, 2020
• Last Updated: October 3, 2024

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share