Integrated Discovery and Development of Innovative TB Diagnostics

Completed

• Conditions: Tuberculosis, Pulmonary
• Interventions: Other: Observational cohort study

• Registration Number: NCT06624501
• Lead Sponsor: Harvard University Faculty of Medicine

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2015-05-01
• Primary Completion: 2018-02-28
• Study First Submitted: 2019-03-05
• Study Completion: 2020-02-28
• Status Verified: 2020-08
• Study First Submitted QC: 2024-10-01
• Last Update Submitted: 2024-10-01
• Study First Posted: 2024-10-03
• Last Update Posted: 2024-10-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1450

Inclusion Criteria

Not provided

Exclusion Criteria

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Children and adults	Observational cohort study	Children with symptoms of TB and adults with smear-positive or smear-negative pulmonary TB.

Primary Outcome Measures

Name	Time	Method
Sensitivity for detection of Mtb, by sample type	Baseline	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).