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

Pelvic Organ Prolapse Clinical Trial

Official title:

Autoimmume/Inflammatory Syndrome Induced by Adjuvants (ASIA Syndrome) Caused by Polypropylene Mesh Implantation - a Pilot Study for Diagnostics and Treatment

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06363903
• Other study ID #: 2022-MMC-051
• Status: Recruiting
• Start date: May 9, 2022
• Est. completion date: May 2025

Study information

• Verified date: April 2024
• Source: Maxima Medical Center
• Contact: Willem AR Zwaans, MD PhD
• Phone: +31408888550
• Email: willem.zwaans[@]mmc.nl
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: May 2025
• Est. primary completion date: May 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Autoimmune Diseases
• Autoimmunity
• Hernia, Inguinal
• Implant Complication
• Inguinal Hernia
• Pelvic Organ Prolapse
• Prolapse
• Stress Urinary Incontinence
• Systemic Autoimmune Disease
• Urinary Incontinence
• Urinary Incontinence, Stress

Intervention

Diagnostic Test:
• mesh allergy test
a 5 mm^2 part of polypropylene mesh will be dissolved in 1 mL Methyl ethyl ketone (MEK), 25 microliters of this solution will be topically applied in a Finn chamber, and a reaction to the topical applicant will be assessed within 48 hours after application.
• blood tests
Blood tests for diagnosis of autoimmune diseases will be performed

Procedure:
• Mesh removal
If wish for mesh removal persists, this procedure can be performed after separate informed consent (within the study), as standard practice of care.

Locations

Country	Name	City	State
Netherlands	Amsterdam UMC	Amsterdam	Noord-Holland
Netherlands	Maastricht University Medical Centre	Maastricht	Limburg
Netherlands	Maxima Medical Centre	Veldhoven	Noord-Brabant

Sponsors (3)

Lead Sponsor	Collaborator
Maxima Medical Center	Amsterdam UMC, Maastricht University Medical Center

Country where clinical trial is conducted

Netherlands, 

References & Publications (9)

Chughtai B, Sedrakyan A, Mao J, Eilber KS, Anger JT, Clemens JQ. Is vaginal mesh a stimulus of autoimmune disease? Am J Obstet Gynecol. 2017 May;216(5):495.e1-495.e7. doi: 10.1016/j.ajog.2016.12.021. Epub 2016 Dec 26. — View Citation

Chughtai B, Thomas D, Mao J, Eilber K, Anger J, Clemens JQ, Sedrakyan A. Hernia repair with polypropylene mesh is not associated with an increased risk of autoimmune disease in adult men. Hernia. 2017 Aug;21(4):637-642. doi: 10.1007/s10029-017-1591-1. Epub 2017 Feb 23. — View Citation

Cohen Tervaert JW. Autoinflammatory/autoimmunity syndrome induced by adjuvants (Shoenfeld's syndrome) in patients after a polypropylene mesh implantation. Best Pract Res Clin Rheumatol. 2018 Aug;32(4):511-520. doi: 10.1016/j.berh.2019.01.003. Epub 2019 Mar 1. — View Citation

Denman MA, Gregory WT, Boyles SH, Smith V, Edwards SR, Clark AL. Reoperation 10 years after surgically managed pelvic organ prolapse and urinary incontinence. Am J Obstet Gynecol. 2008 May;198(5):555.e1-5. doi: 10.1016/j.ajog.2008.01.051. Epub 2008 Mar 20. — View Citation

Kowalik CR, Zwolsman SE, Malekzadeh A, Roumen RMH, Zwaans WAR, Roovers JWPR. Are polypropylene mesh implants associated with systemic autoimmune inflammatory syndromes? A systematic review. Hernia. 2022 Apr;26(2):401-410. doi: 10.1007/s10029-021-02553-y. Epub 2022 Jan 12. — View Citation

Lowenstein E, Moller LA, Laigaard J, Gimbel H. Reoperation for pelvic organ prolapse: a Danish cohort study with 15-20 years' follow-up. Int Urogynecol J. 2018 Jan;29(1):119-124. doi: 10.1007/s00192-017-3395-3. Epub 2017 Jul 3. — View Citation

Muller P, Gurol-Urganci I, Thakar R, Ehrenstein MR, Van Der Meulen J, Jha S. Impact of a mid-urethral synthetic mesh sling on long-term risk of systemic conditions in women with stress urinary incontinence: a national cohort study. BJOG. 2022 Mar;129(4):664-670. doi: 10.1111/1471-0528.16917. Epub 2021 Oct 5. — View Citation

Slooter GD, Zwaans WAR, Perquin CW, Roumen RMH, Scheltinga MRM. Laparoscopic mesh removal for otherwise intractable inguinal pain following endoscopic hernia repair is feasible, safe and may be effective in selected patients. Surg Endosc. 2018 Mar;32(3):1613-1619. doi: 10.1007/s00464-017-5824-2. Epub 2017 Aug 24. — View Citation

Zwaans WA, Perquin CW, Loos MJ, Roumen RM, Scheltinga MR. Mesh Removal and Selective Neurectomy for Persistent Groin Pain Following Lichtenstein Repair. World J Surg. 2017 Mar;41(3):701-712. doi: 10.1007/s00268-016-3780-y. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Positive diagnostic tests	Rate of positive diagnostic tests of either blood draws or MAT as an indication for presence of an autoimmune disease.	At inclusion. There is no need to repeat this test after first result.
Secondary	Autoimmune complaints and objective findings in immunologic blood test	Association between subjective outcomes of autoimmune/inflammatory symptoms and objective findings in blood tests that indicate presence of inflammation or autoimmunity.	At inclusion, questionnaires repeated after 6 and 12 months. Blood tests will not be repeated after tests at inclusion.
Secondary	Autoimmune complaints and objective findings in mesh allergy test (MAT)	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.	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)
Secondary	Mesh removal and subjective complaints	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.	Follow-up 1 year after surgery. At inclusion, questionnaires repeated after 6 and 12 months.
Secondary	Mesh histopathology	All explanted meshes will be examined histopathologically to check for granulomatous inflammatory or acute inflammatory reactions surrounding the explant.	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.
Secondary	Patient demographics	Baseline patient demographics will be collected for all included patients, as well as for patients undergoing surgical mesh removal. Descriptive analysis will be performed.	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.