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

• ClinicalTrials.gov Identifier: NCT02156102
• Recruitment Status: Recruiting
• First Posted: June 5, 2014
• Last Update Posted: April 25, 2023
• Sponsor: National Human Genome Research Institute (NHGRI)
• Information provided by (Responsible Party): National Institutes of Health Clinical Center (CC) ( National Human Genome Research Institute (NHGRI) )

Tracking Information

• First Submitted Date: June 4, 2014
• First Posted Date: June 5, 2014
• Last Update Posted Date: April 25, 2023
• Actual Study Start Date: June 16, 2014
• Estimated Primary Completion Date: December 31, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 16, 2021)

• 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
• 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
• 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

Original Primary Outcome Measures (submitted: June 4, 2014)

• The second primary outcome of this research [ Time Frame: May 2014-August 20 ]
• The first primary outcome of this research [ Time Frame: May 2014-May 2015 ]

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures (submitted: June 4, 2014): The secondary outcomes of this research [ Time Frame: May 2014-April 2015 ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Insights Into Microbiome and Environmental Contributions to Sickle Cell Disease and Leg Ulcers Study (INSIGHTS Study)
• Official Title: Insights Into Microbiome and Environmental Contributions to Sickle Cell Disease and Leg Ulcers

Brief 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.

Detailed 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.

• Study Type: Observational
• Study Design: Observational Model: Case-Only; Time Perspective: Cross-Sectional
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• 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.

Condition

• Genetic Disease
• Genomics

• Intervention: Not Provided

Study Groups/Cohorts

• 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

Publications *

• 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.
• 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.
• 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.
• Raymond MB, Cooper KE, Parker LS, Bonham VL. Practices and Attitudes toward Returning Genomic Research Results to Low-Resource Research Participants. Public Health Genomics. 2021;24(5-6):241-252. doi: 10.1159/000516782. Epub 2021 Jul 6.
• Desine S, Eskin L, Bonham VL, Koehly LM. Social support networks of adults with sickle cell disease. J Genet Couns. 2021 Oct;30(5):1418-1427. doi: 10.1002/jgc4.1410. Epub 2021 Apr 12.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 8, 2020): 550
• Original Estimated Enrollment (submitted: June 4, 2014): 200
• Estimated Study Completion Date: December 31, 2025
• Estimated Primary Completion Date: December 31, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

• 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).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Hasmin C Ramirez; (301) 435-6817; hasmin.ramirez@nih.gov

Contact: Vence L Bonham, J.D.; (301) 594-3973; bonhamv@nhgri.nih.gov

• Listed Location Countries: Sierra Leone, United States

Administrative Information

• NCT Number: NCT02156102
• Other Study ID Numbers: 140125; 14-HG-0125
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: National Institutes of Health Clinical Center (CC) ( National Human Genome Research Institute (NHGRI) )
• Original Responsible Party: Same as current
• Current Study Sponsor: National Human Genome Research Institute (NHGRI)
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Vence L Bonham, J.D.; National Human Genome Research Institute (NHGRI)

• PRS Account: National Institutes of Health Clinical Center (CC)
• Verification Date: November 10, 2022