Metagenomics Next-generation Sequencing Approach to Detect Microbial DNA/RNA Overtime in Individuals Undergoing Hematopoietic Stem Cell Transplant

Metagenomics Next-Generation Sequencing Approach to Detect Microbial DNA/RNA Overtime in Individuals Undergoing Hematopoietic Stem Cell Transplant

Infections are a major cause of morbidity and mortality in patients undergoing hematopoietic stem cell transplant (HSCT). The purpose of this study is to evaluate if metagenomic next-generation sequencing (mNGS) can detect microbial signatures in people undergoing HSCT, and if microbial identification can be correlated with clinical features of infection (e.g., fever). Participants undergoing HSCT as part of other studies at the NIH Clinical Center (CC) will provide blood before the transplant and through 6 months after. Total nucleic acid will be extracted from plasma and subjected to mNGS.

The primary objective of this study is to investigate if by using plasma and an mNGS approach, we can detect bacterial, fungal, protozoan, or viral DNA/RNA over time, in immunocompromised patients undergoing transplantation.

Secondary objectives are to: (1) To correlate microbial identification with episodes of fever or clinical suspicion of infection; and to (2) correlate change in microbial signatures in patients with suspected immune reconstitution inflammatory syndrome.

The study is conducted at the NIH Clinical Center. Participants, aged 3 years and older, on other research studies at the NIH CC who are undergoing HSCT are invited to take part of this study. Expected participation is up to six months.

Study Overview

• Status: Recruiting
• Conditions: Hematopoietic Stem Cell Transplantation

Detailed Description

Study Description:

Infections are a major cause of morbidity and mortality in patients undergoing hematopoietic stem cell transplant (HSCT). The purpose of this study is to evaluate if metagenomic next-generation sequencing (mNGS) can detect microbial signatures in people undergoing HSCT, and if microbial identification can be correlated with clinical features of infection (e.g., fever).

Participants undergoing HSCT as part of other studies at the NIH Clinical Center (CC) will provide blood before the transplant and through 6 months after. Total nucleic acid will be extracted from plasma and subjected to mNGS.

Objectives:

Primary:

To investigate if by using plasma and an mNGS approach, we can detect bacterial, fungal, protozoan, or viral DNA/RNA over time, in immunocompromised patients undergoing transplantation.

Secondary:

1. To correlate microbial identification with episodes of fever or clinical suspicion of infection.
2. To correlate change in microbial signatures in patients with suspected immune reconstitution inflammatory syndrome.

Endpoints:

Primary:

Comparison of mNGS results to routine clinical test results (microbiology and/or pathology)

Secondary:

1. Calculation of frequencies of different microbial identifications as it relates to the development of fever or microbiologically/clinically defined infection.
2. Changes in different microbial signatures over time

• Study Type: Observational
• Enrollment (Estimated): 30

Contacts and Locations

• Study Contact: Name: Mary M Czech, M.D.; Phone Number: (240) 447-9109; Email: mary.czech@nih.gov
• Study Contact Backup: Name: Sanchita Das, M.D.; Phone Number: (301) 496-5668; Email: sanchita.das@nih.gov

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Recruiting
      • National Institutes of Health Clinical Center
      • Contact: NIH Clinical Center Office of Patient Recruitment (OPR); Phone Number: TTY dial 711 800-411-1222; Email: ccopr@nih.gov

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Participants aged 3 years and older on other research studies at the NIH CC who are undergoing HSCT as part of that study.

Description

• INCLUSION CRITERIA:

In order to be eligible to participate in this study; an individual must meet all the following criteria:

1. Male or female, aged 3 years or older.
2. Co-enrolled on another study at the NIH CC, under which they will undergo HSCT.
3. Stated willingness to comply with all study procedures and availability for the duration of the study.
4. Ability of subject or Legally Authorized Representative (LAR) to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA:

An individual with any condition that, in the opinion of the investigator, contraindicates participation in this study, will be excluded.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
All HSCT patients; Male or female, aged 3 years or older.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Any positive clinical results for each of 5 pathogen categories	Research blood draw at screening, during fever episodes and at follow up days 30, 100 and 180 (+/- 7 days).	Six months

Collaborators and Investigators

• Sponsor: National Institutes of Health Clinical Center (CC)
• Investigators: Principal Investigator: Sanchita Das, M.D., National Institutes of Health Clinical Center (CC)

Publications and helpful links

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): April 9, 2025
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): December 30, 2030

Study Registration Dates

• First Submitted: March 29, 2025
• First Submitted That Met QC Criteria: March 29, 2025
• First Posted (Actual): April 1, 2025

Study Record Updates

• Last Update Posted (Actual): April 6, 2026
• Last Update Submitted That Met QC Criteria: April 3, 2026
• Last Verified: April 2, 2026

More Information

Terms related to this study

• Keywords: Hematopoietic stem cell transplant (HSCT); Microbial DNA/RNA
• Other Study ID Numbers: 10001923; 001923-CC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No