Molecular Mechanisms Associated With Breast Implant Complications (MMABIC)

Bacterial biofilms cause implant failures, chronic inflammation, and immune polarization. The study investigates the possible role of bacterial biofilm as a factor in the etiology of Breast Implant Illness. Three patient cohorts will be studied (A) Subjects with breast implant with BII manifestations (B) Subjects with breast implants without BII manifestations (C) Subjects without breast implants who underwent breast surgery procedure. Blood, surgically discarded tissue, implants, and associated capsules will be collected through this protocol.

Study Overview

• Status: Recruiting
• Conditions: Breast Implant; Complications; Infection or Inflammation

Detailed Description

Breast implants were first introduced in 1962. It is estimated that 10 million women worldwide, including three million Americans have breast implants. There has been increased identification of patients experiencing a constellation of symptoms related to their implants. For breast implants, these symptoms are often associated with autoimmune and connective tissue disorders (CTD) and have been referred to as Breast Implant Illness (BII). A growing number of patients 30,000 annually are seeking to have their breast implants removed. In view of the implant associated complications, the US Food and Drug Administration (FDA) has placed a black box warning on breast implants. Limited research has resulted in a void in the prognosis of this surgical problem. Bacterial biofilms are becoming a major concern for medical device implants. Bacterial biofilms cause implant failures, chronic inflammation, and immune polarization. The study investigates the possible role of bacterial biofilm as a factor in the etiology of BII.

This research studies oxilidized lipids (oxylipins). These are metabolities formed as a result of host-biofilm interaction. The presence of oxylipins will be studied in peri-prosthetic tissue post-biofilm infection and in systemic circulation. Oxylipins are immunogenic. Hence, the investigators will also study the abundance of immune cells T cells and macrophages (types and subtypes) and associated cytokines.

• Study Type: Observational
• Enrollment (Estimated): 1000

Contacts and Locations

• Study Contact: Name: Mithun Sinha, PhD.; Phone Number: 3172782713; Email: mitsinha@iu.edu
• Study Contact Backup: Name: Bryce Hockman; Phone Number: 3172782715; Email: bbhockma@iu.edu

Study Locations

• United States
  • Indiana
    • Carmel, Indiana, United States, 46032
      • Recruiting
      • IU Health North Hospital
      • Contact: Jason VonDerHaar, MD
    • Carmel, Indiana, United States, 46290
      • Recruiting
      • Meridian Plastic Surgeons
      • Contact: Christine Kelley-Patteson, MD
    • Indianapolis, Indiana, United States, 46202
      • Recruiting
      • IU Health Methodist Hospital
      • Contact: Bryce Hockman; Phone Number: 3172782715; Email: bbhockma@iu.edu
      • Contact: Mary Lester; Email: melester@iupui.edu
      • Sub-Investigator: Aladdin Hassanein, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

The study population focuses on females, ages 18 years or older, that are either undergoing removal of breast implants or undergoing breast surgery. Participants must be willing to comply with protocol instructions and possess the mental capabilities to understand the procedures, risks, and benefits of the study. Additionally, participants that are pregnant will not be eligible for participation. Lastly, participants that are deemed immunodeficient or currently taking immunosuppressive medications will be ineligible for participation.

Description

Inclusion Criteria for breast implant subjects:

• Age greater than or equal to 18 years
• Undergoing removal of breast implant
• Willing and able to comply with protocol instructions

Inclusion Criteria for subjects undergoing breast surgeries (other than implant removal)

• Age greater than or equal to 18 years
• Undergoing breast surgery
• Willing and able to comply with protocol instructions

Exclusion Criteria:

• Individuals who are deemed unable to understand the procedures, risks, and benefits of the study, (i.e., unable to provide informed consent)
• Pregnant females
• Immunodeficiency (HIV/AIDS, SCID)
• Currently on immunosuppressive medications
• Prisoners

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
BII Subjects; Subjects with breast implants having BII manifestations.
Non-BII Subjects; Subjects with breast implants with no reported BII symptoms.
Subjects without Breast Implants; Subjects without breast implants.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence of Biofilm in Breast Tissue	During a clinically scheduled breast surgery, breast tissue specimens will be taken from surgically discarded tissue. The specimens from both breast implant subjects and control subjects (those undergoing breast surgery for a reason other than implant removal) will be analyzed to determine the presence of bacterial biofilm.	Through study completion, an average of 1 year
Analysis of host-biofilm interaction mediated oxylipins from blood	Prior to a clinically scheduled breast surgery, 20 milliliters of blood will be collected during the pre-operative surgical preparations. The blood samples from both breast implant subjects and control subjects (those undergoing breast surgery for a reason other than implant removal) will be analyzed for host-biofilm interaction mediated oxylipins.	Through study completion, an average of 1 year
Cytokine analysis will be performed on breast tissue	During a clinically scheduled breast surgery, breast tissue specimens will be taken from surgically discarded tissue. The specimens from both breast implant subjects and control subjects (those undergoing breast surgery for a reason other than implant removal) will undergo cytokine analysis.	Through study completion, an average of 1 year
Analysis of host-biofilm interaction mediated oxylipins from breast tissue	During a clinically scheduled breast surgery, breast tissue specimens will be taken from surgically discarded tissue. The specimens from both breast implant subjects and control subjects (those undergoing breast surgery for a reason other than implant removal) will undergo oxylipin analysis.	Through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CD4+ Immunological Activation due to Host Implant Interaction	Determining activation of CD4+ immune cells	Through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Indiana University
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID); National Institutes of Health (NIH)
• Investigators: Principal Investigator: Mithun Sinha, PhD., Indiana University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2021
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: January 17, 2023
• First Submitted That Met QC Criteria: February 16, 2023
• First Posted (Actual): February 21, 2023

Study Record Updates

• Last Update Posted (Estimated): March 6, 2024
• Last Update Submitted That Met QC Criteria: March 4, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation
• Other Study ID Numbers: 2003674175; R21AI171932 (U.S. NIH Grant/Contract); R01AI165958 (U.S. NIH Grant/Contract)

Drug and device information, study documents

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