Clinical trial NCT06363903: ASIA-Mesh: a Pilot Study for Diagnostics and Treatment on ASIA Syndrome Caused by Polypropylene Mesh Implantation
Official title: Autoimmume/Inflammatory Syndrome Induced by Adjuvants (ASIA Syndrome) Caused by Polypropylene Mesh Implantation - a Pilot Study for Diagnostics and Treatment
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Autoimmunity
Inguinal Hernia
Stress Urinary Incontinence
Pelvic Organ Prolapse
Implant Complication
Systemic Autoimmune Disease
Keywords: ASIA; Polypropylene; Mesh reaction; Implant; Pilot
Lead sponsor: Maxima Medical Center
Sponsor class: OTHER
Collaborators: name: Amsterdam UMC
name: Maastricht University Medical Center
First posted: 2024-04-12
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with suspected auto-immune/inflammatory response or ASIA syndrome will be recruited to one of the outpatient clinics that accept patients with ASIA syndrome complaints. Only referrals will be accepted and no active recruitment will be undertaken.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Positive diagnostic tests
timeFrame: At inclusion. There is no need to repeat this test after first result.
Secondary outcomes:
measure: Autoimmune complaints and objective findings in immunologic blood test
timeFrame: At inclusion, questionnaires repeated after 6 and 12 months. Blood tests will not be repeated after tests at inclusion.
measure: Autoimmune complaints and objective findings in mesh allergy test (MAT)
timeFrame: 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)
measure: Mesh removal and subjective complaints
timeFrame: Follow-up 1 year after surgery. At inclusion, questionnaires repeated after 6 and 12 months.
measure: Mesh histopathology
timeFrame: 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.
measure: Patient demographics
timeFrame: 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.
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Centre
state: Limburg
city: Veldhoven
country: Netherlands
facility: Maxima Medical Centre
state: Noord-Brabant
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC
state: Noord-Holland
Study officials:
affiliation: Maxima Medical Center
name: Willem AR Zwaans, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Maxima Medical Center
name: Maurits JC Gielen, MD
role: STUDY_DIRECTOR
References:
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.
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.
citation: 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.
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.
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.
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.
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.
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.
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.