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

Genetic Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02156102
• Other study ID #: 140125
• Secondary ID: 14-HG-0125
• Status: Recruiting
• Start date: June 16, 2014
• Est. completion date: December 31, 2025

Study information

• Verified date: May 1, 2024
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Hasmin C Ramirez
• Phone: (301) 435-6817
• Email: hasmin.ramirez[@]nih.gov
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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. There is variation in the incidence and duration of SCD leg ulcers.

They are often very painful, resistant to treatment, and recurrent in nature. 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. To achieve these goals, we will: (1) characterize the leg skin microbiome of SCD participants living with and without leg ulcers within the United States and Sierra Leone; (2) collect and analyze psychosocial and physical environmental data of individuals with SCD without leg ulcers and with leg ulcers; (3) examine the psychosocial impact of leg ulcers on individuals with SCD by conducting a qualitative phase to explore the individual experiences to understand the physical function, stigma, and self-esteem associated with those with active, recurrent, or single-occurrence presentations of leg ulcers; and (4) explore what factors influence psychological resilience, to examine the relationship of psychological resilience to the health outcomes of an adult population living with sickle cell disease in the U.S. and in Sierra Leone. This will provide us the opportunity to understand the complexity of participants' health, health care experiences and quality of life.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 550
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

• INCLUSION CRITERIA:

Each subject must meet all of the following inclusion criteria during the screening process in order to participate in the study:

• 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 singleoccurrence presentation of a leg ulcer(s).

• For the resilience study analysis: this 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 subject 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).

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Genetic Disease
• Genetic Diseases, Inborn
• Genomics
• Leg Ulcer

Locations

Country	Name	City	State
Sierra Leone	University of Sierra Leone, College of Medicine and Allied Health Services	Freetown
United States	National Institutes of Health Clinical Center	Bethesda	Maryland
United States	Montefiore Medical Center/Albert Einstein College of Medicine	Bronx	New York

Sponsors (1)

Lead Sponsor	Collaborator
National Human Genome Research Institute (NHGRI)

Countries where clinical trial is conducted

United States,  Sierra Leone, 

References & Publications (3)

Crouch EM, Bonham VL, Abdallah K, Buscetta A, Vinces G, Heo M, Minniti CP. Nutritional supplement profile of adults with sickle cell disease. Am J Hematol. 2018 May 4:10.1002/ajh.25129. doi: 10.1002/ajh.25129. Online ahead of print. No abstract available. — View Citation

Minniti CP, Eckman J, Sebastiani P, Steinberg MH, Ballas SK. Leg ulcers in sickle cell disease. Am J Hematol. 2010 Oct;85(10):831-3. doi: 10.1002/ajh.21838. — View Citation

Umeh NI, Ajegba B, Buscetta AJ, Abdallah KE, Minniti CP, Bonham VL. The psychosocial impact of leg ulcers in patients with sickle cell disease: I don't want them to know my little secret. PLoS One. 2017 Oct 18;12(10):e0186270. doi: 10.1371/journal.pone.0186270. eCollection 2017. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The skin microbiome	Employ genomic approaches to characterize the skin microbiome in individuals living with SCD with and without leg ulcers	Assessment occurs on date of visit.
Primary	The factors that impact quality of life	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.
Primary	Sickle Cell disease severity measure	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.

External Links

•   NIH Clinical Center Detailed Web Page