Insights Into Microbiome and Environmental Contributions to Sickle Cell Disease and Leg Ulcers Study (INSIGHTS Study)

October 28, 2026 updated by: National Human Genome Research Institute (NHGRI)

Insights Into Microbiome and Environmental Contributions to Sickle Cell Disease and Leg Ulcers

Background:

- People with sickle cell disease and other blood disorders sometimes get chronic leg ulcers. These are wounds that develop on the skin and don t go away. Current treatments do not work very well, so researchers want to learn more about why the ulcers happen. They want to find out which bacteria may cause it, and if external factors play a role.

Objective:

- To study social and environmental factors of sickle cell disease and the causes of sickle cell disease leg ulcers.

Eligibility:

- People age 18 and older who have sickle cell disease or another red cell disorder, with or without an active leg ulcer.

Design:

  • Participants will have a medical history and clinical evaluation. They will also have blood drawn.
  • Participants will complete questionnaires about their life, health, environment, stress, and other topics.
  • Participants may provide a small sample of hair.
  • Participants will be asked to collect a small amount of saliva.
  • Participants with leg ulcers will have their skin microbiome sampled. The microbiome is all of the microbes (bacteria and and/or fungi) and their genes in and on the body. Researchers will use swabs to collect skin samples. Photographs will be taken of the skin sample area.
  • Some participants without leg ulcers also will have their skin microbiome sampled.
  • Some participants who have their skin microbiome sampled will return for a second visit. At this visit, their microbiome will be resampled. It will take place more than 30 days after the first visit.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Detailed Description

Study Description:

Leg ulcers are a serious and debilitating complication of sickle cell disease (SCD). This study will explore microbial, genomic, and environmental (social and physical) factors, that may influence the onset and progression of leg ulcer formation and delayed healing in individuals living with SCD. The etiology of SCD-associated leg ulcers is unclear, and we hypothesize that predisposition to developing leg ulcers is multifactorial. This multisite study is an exploratory study of the microbiome and environment of individuals living with sickle cell disease leg ulcers. The study s objective is to identify triggers that may be integral in leg ulcer onset and progression. The central goal of this study is to obtain an improved understanding of the participants clinical phenotype, leg ulcer microbiome and the psychosocial and environmental factors that may impact this complication.

Objectives:

Primary Objective:

Employ genomic approaches to characterize the skin microbiome in individuals living with SCD with and without leg ulcers.

Secondary Objective:

  1. Employ social science research measures to identify psychosocial and physical environmental factors that impact quality of life in individuals living with SCD with and without leg ulcers.
  2. Develop new measure of severity for SCD that integrates clinical outcomes and the quality of life of the participant.
  3. Develop guidelines for researchers to address the needs of diverse and under-resourced groups in genetic research.

Endpoints:

Primary Endpoint:

To characterize the microbiome of leg ulcers in SCD.

Secondary Endpoints:

  1. To characterize the phenotypic variation in SCD.
  2. To identify similarities and differences of the microbial signatures of chronic diabetic foot ulcers and SCD leg ulcers.
  3. To investigate physical and psychosocial environmental indicators that impact quality of life in individuals living with SCD with and without leg ulcers.
  4. To determine if an association exists between the microbiome (microbial diversity) of SCD leg ulcers and the quality of life (psychosocial and physical environment) indicators of individuals with SCD leg ulcers.
  5. To determine if an association exists between the microbiome (microbial diversity) of SCD leg ulcers and clinical phenotype of individuals with SCD leg ulcers.
  6. To determine how leg ulcers influence one s physical function and one s perceptions of stigma and self-esteem.
  7. To identify factors that are indicators of both quality of life and clinical severity of the participant.
  8. To identify specific psychosocial and environmental factors related to resilience in our study population.
  9. To investigate current practices and policies around the return of secondary findings in genome sequencing studies in under-resourced study participant populations, and to explore ethical and clinical policies for returning secondary findings by examining various practices within the research community.
  10. To investigate SCD variation in phenotype, microbiome, physical and psychosocial environments in a cohort in Sierra Leone.
  11. To compare similarities and differences in phenotype, microbiome, physical and psychosocial environments between U.S. and Sierra Leone cohorts.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
405

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Sierra Leone
      • Freetown, Sierra Leone
        • University of Sierra Leone, College of Medicine and Allied Health Services
  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Institutes of Health Clinical Center
    • New York
      • The Bronx, New York, United States, 10467
        • Montefiore Medical Center/Albert Einstein College of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 120 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

This is a descriptive study of individuals living with sickle cell diseases (SCD) with and without leg ulcers (accrual goal 550 participants). Leg ulcers are not observed in all individuals with SCD and we are interested in understanding why certain individuals develop leg ulcers. We will seek to include age-matched patients without leg ulcers for the microbiome phase of the study. We will recruit and sample male or female adult participants with ulcers, currently without leg ulcers, and those with no previous history of leg ulcers. To ensure we recruit an adequate number of participants with and without leg ulcers, we will rely on multiple recruiting methods, which will include posting flyers, social media advertisements, and/or referrals.

Description

  • INCLUSION CRITERIA:

We will enroll up to four-hundred and fifty (N=450) participants in the microbiome sampling cohort. In addition to the 300 SCD leg ulcer microbiome participants, we will recruit up to an additional 200-250 SCD participants that will complete the clinical evaluation, (including blood sample) and survey instruments for a total of up to 550 participants at three sites, NIH (n=200) and MMC (n=100), and Sierra Leone (n=250).

Of the total participants, we will resample the microbiome of up to 75 individuals from each of the 3 initial sampling groups: SCD with, without and never had SCD leg ulcers. Of those 75 individuals who are sampled longitudinally, those with clinically interesting cases may be sampled at multiple intervals.

All sampling, surveys, and processing of samples will take place at the NIH Clinical Center the second site, MMC, or in Sierra Leone. All samples will be stored at NIH.

To be eligible to participate in this study, an individual must meet all of the following criteria:

  • All subjects must have a diagnosis of sickle cell disease (HbSS, HgSC, HbSB 0 or HBSB+)
  • Be at least 18 years old.
  • Provide written informed consent.
  • For the Qualitative phase: must have a recurrent, active, or single-occurrence presentation of a leg ulcer(s).
  • For the resilience study analysis: cohort will be determined by the research team based on the results of part I of this analysis. For part I, the inclusion criteria are that the individual must have enrolled and completed the INSIGHTS study.

EXCLUSION CRITERIA:

Any individual that meets any of the following criteria during baseline evaluation will be excluded from the study:

  • Pediatric population (<18 years old)
  • Participants for microbiome study (only) who have received oral and/or topical antibiotics or antifungals < 2 weeks prior to enrolling in the study for leg ulcers (for those with leg ulcers only)
  • Subjects presenting with clinically diagnosed bacterial infection (i.e. clinical appearance, clinical judgment, fever, redness around ulcer, purulent drainage etc.) at the site of ulceration. (This can only be diagnosed clinically by the research nurse during sampling

and is only applicable to those with leg ulcers only).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: CASE_ONLY
  • Time Perspectives: CROSS_SECTIONAL

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Microbiome with active Leg Ulcer

We will recruit and obtain microbiome samples from male or female adult participants with active leg ulcers and sickle cell disease.
Microbiome with no active Leg Ulcer

We will recruit and obtain microbiome samples from male or female adult participants without active leg ulcers but do have sickle cell disease.
Non-microbiome participants

We will recruit but not obtain microbiome samples from participants with sickle cell disease

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
The skin microbiome
Time Frame: Assessment occurs on date of visit.

Employ genomic approaches to characterize the skin microbiome in individuals living with SCD with and without leg ulcers
Assessment occurs on date of visit.
The factors that impact quality of life
Time Frame: Assessment occurs on date of visit.

Employ social science research measures to identify psychosocial and physical environmental factors that impact quality of life in individuals living with SCD with and without leg ulcers
Assessment occurs on date of visit.
Sickle Cell disease severity measure
Time Frame: Assessment occurs on date of visit.

Develop new measure of severity for SCD that integrates clinical outcomes and the quality of life of the participant
Assessment occurs on date of visit.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
National Human Genome Research Institute (NHGRI)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Laura M Koehly, Ph.D., National Human Genome Research Institute (NHGRI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 16, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 1, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 1, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 4, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 4, 2014

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 5, 2014

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 29, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 28, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 9, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 140125
  • 14-HG-0125

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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