ASIA-Mesh: a Pilot Study for Diagnostics and Treatment on ASIA Syndrome Caused by Polypropylene Mesh Implantation

Recruiting

• Conditions: Pelvic Organ Prolapse; Systemic Autoimmune Disease; Autoimmunity; Inguinal Hernia; Stress Urinary Incontinence; Implant Complication
• Interventions: Diagnostic Test: mesh allergy test; Diagnostic Test: blood tests; Procedure: Mesh removal

• Registration Number: NCT06363903
• Lead Sponsor: Maxima Medical Center

Brief Summary

In the present pilot study, a possible relation between the implantation of PP mesh for inguinal hernia, vaginal prolapse and SUI repair and subsequent systemic auto-immune complaints is investigated by testing immunologic and allergic responses in fifty patients with suspected ASIA syndrome. Additional value of MAT is investigated and effectiveness of (partial) PP mesh removal for these complaints is assessed. If so, a profound insight in diagnostics and treatment for systematic complaints will be attained that may provide opportunities for future diagnostics.

Detailed Description

Worldwide there is a lot of commotion about the effects and complications of various implants. In analogy to patients with silicone breast implants, some patients report various systemic complaints following inguinal polypropylene (PP) mesh implantation, suggesting 'Autoinflammatory/Autoimmunity Syndrome Induced by Adjuvants' (ASIA; Shoenfeld's syndrome) or some other suspected systemic auto-immune/inflammatory response. Although an evidence-based and causal relationship is lacking, patients report serious complaints. Therefore, the investigators recently started seeing these patients at the outpatient clinic and developed a diagnostic workup, including an elaborate anamnesis, conventional immunologic analyses and mesh allergy testing (MAT). Further, in case the implant is removed as part of the treatment due to a persistent wish of the patient, the PP explant will be histologically examined to find additional cues for an auto-immune/inflammatory response (and thus ASIA). So far, evidence on the optimal diagnostic workup for patients with suspected ASIA syndrome is lacking completely.

Study Timeline

• Study Start: 2022-05-09
• Study First Submitted: 2024-02-26
• Status Verified: 2024-04
• Study First Submitted QC: 2024-04-10
• Last Update Submitted: 2024-04-10
• Study First Posted: 2024-04-12
• Last Update Posted: 2024-04-12
• Primary Completion: 2024-05
• Study Completion: 2025-05

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

• Patients >18 years of age and written informed consent obtained;
• Suspected ASIA syndrome after elective hernia, pelvic organ prolapse (POP) surgery, or stress urinary incontinence (SUI) repair, defined as three major ASIA criteria (Table 1), of which the exposure to an external stimulus (PP mesh) is one;
• ASIA complaints evolved after the implantation of PP mesh and were not present before the surgical repair.

Exclusion Criteria

• Known auto-immune disorders;
• Known malignancies;
• (Low grade) infections or other inflammatory diseases at time of surgery;
• Cognitively impaired individuals.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Included patients	mesh allergy test	Patients included with index operation that are referred to a participating outpatient clinic and who present with ASIA Syndrome-like complaints occurring after PP implant placement.
Included patients	blood tests	Patients included with index operation that are referred to a participating outpatient clinic and who present with ASIA Syndrome-like complaints occurring after PP implant placement.
Included patients	Mesh removal	Patients included with index operation that are referred to a participating outpatient clinic and who present with ASIA Syndrome-like complaints occurring after PP implant placement.

Primary Outcome Measures

Name	Time	Method
Positive diagnostic tests	At inclusion. There is no need to repeat this test after first result.	Rate of positive diagnostic tests of either blood draws or MAT as an indication for presence of an autoimmune disease.

Secondary Outcome Measures

Name	Time	Method
Autoimmune complaints and objective findings in immunologic blood test	At inclusion, questionnaires repeated after 6 and 12 months. Blood tests will not be repeated after tests at inclusion.	Association between subjective outcomes of autoimmune/inflammatory symptoms and objective findings in blood tests that indicate presence of inflammation or autoimmunity.
Autoimmune complaints and objective findings in mesh allergy test (MAT)	At inclusion, questionnaires repeated after 6 and 12 months. MAT will not be repeated after test at inclusion due to either a positive test (and therefore emergence of immune memory cells) or negative test (and therefore no immune response to mesh at t0)	Association between subjective outcomes of autoimmune/inflammatory symptoms and objective findings of the mesh allergy test (MAT) that either indicate presence of intolerance to mesh, or indicate no dermal/allergic reaction to the material of the mesh.
Mesh removal and subjective complaints	Follow-up 1 year after surgery. At inclusion, questionnaires repeated after 6 and 12 months.	Success rate of mesh removal for the resolution of subjective complaints using Tissue Connective Disease Screening Questionnaire (CSQ) and Patient Global Impression of Improvement (PGI-I) questionnaire and ASIA symptoms.
Mesh histopathology	Directly after surgery if surgical mesh removal is deemed safe by the surgeon and preferred by the patient. As attempts will be made to completely remove the mesh, mesh histopathology will only be performed once.	All explanted meshes will be examined histopathologically to check for granulomatous inflammatory or acute inflammatory reactions surrounding the explant.
Patient demographics	At the start of the inclusion period demographics will be recorded. Demographics will also be recorded for the population undergoing surgery, in combination with Outcome measure 3 of subjective complaints.	Baseline patient demographics will be collected for all included patients, as well as for patients undergoing surgical mesh removal. Descriptive analysis will be performed.

Trial Locations

Locations (3)

Amsterdam UMC; 🇳🇱 Amsterdam, Noord-Holland, Netherlands

Maastricht University Medical Centre; 🇳🇱 Maastricht, Limburg, Netherlands

Maxima Medical Centre; 🇳🇱 Veldhoven, Noord-Brabant, Netherlands