AutoimmunityNCT06363903
ASIA-Mesh: a Pilot Study for Diagnostics and Treatment on ASIA Syndrome Caused by Polypropylene Mesh Implantation
An observational study of Autoimmunity and Inguinal Hernia, run by Maxima Medical Center at 3 sites in Netherlands.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Autoimmunity, Inguinal Hernia, Stress Urinary Incontinence
- What is being tested?
- mesh allergy test, blood tests and Mesh removal
- Type of treatment
- Surgery or procedure
- How many people
- 50 participants
- Where
- 3 sitesNetherlands
- Study dates
- 9 May 2022to May 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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.
Who cannot join
- Known auto-immune disorders;
- Known malignancies;
- (Low grade) infections or other inflammatory diseases at time of surgery;
- Cognitively impaired individuals.
Trial locations and contacts
3 sites in 1 country.
Netherlands3 sites, 2 recruiting
- Not yet recruiting
Amsterdam UMC
Amsterdam, North Holland, 1105AZ
Prof. Dr. J.P. Roovers
- Active, not recruiting
Maastricht University Medical Centre
Maastricht, Limburg, 6229HX
- Recruiting
Maxima Medical Centre
Veldhoven, North Brabant, 5504DB
Willem AR Zwaans, MD PhD, +31408888550, willem.zwaans@mmc.nl
Maurits JC Gielen, MD
About this study
Official title: Autoimmume/Inflammatory Syndrome Induced by Adjuvants (ASIA Syndrome) Caused by Polypropylene Mesh Implantation - a Pilot Study for Diagnostics and Treatment
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.
Read the 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.
- Conditions
- Autoimmunity, Inguinal Hernia, Stress Urinary Incontinence, Pelvic Organ Prolapse, Implant Complication, Systemic Autoimmune Disease
- Being tested
- mesh allergy test, blood tests, Mesh removal
- Keywords
- ASIA; Polypropylene; Mesh reaction; Implant; Pilot
- Medical subject headings
- Autoimmune Diseases, Hernia, Inguinal, Urinary Incontinence, Stress, Pelvic Organ Prolapse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
mesh allergy testDiagnostic 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 testsDiagnostic test
Blood tests for diagnosis of autoimmune diseases will be performed
Mesh removalProcedure or surgery
If wish for mesh removal persists, this procedure can be performed after separate informed consent (within the study), as standard practice of care.
| Study group | Role | What they receive |
|---|---|---|
| Included patients | 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. Receives: Diagnostic Test: mesh allergy test; Diagnostic Test: blood tests; Procedure: Mesh removal |
What is being measured
The primary outcome is the main question the study is designed to answer.
Positive diagnostic tests
Rate of positive diagnostic tests of either blood draws or MAT as an indication for presence of an autoimmune disease.
Measured: At inclusion. There is no need to repeat this test after first result.
Secondary outcomes (5)
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.
Measured: At inclusion, questionnaires repeated after 6 and 12 months. Blood tests will not be repeated after tests at inclusion.
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.
Measured: 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)
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.
Measured: Follow-up 1 year after surgery. At inclusion, questionnaires repeated after 6 and 12 months.
Mesh histopathology
All explanted meshes will be examined histopathologically to check for granulomatous inflammatory or acute inflammatory reactions surrounding the explant.
Measured: 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.
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.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2024
- Study start9 May 2022
- Primary completionMay 2024 (estimated)
- Study completionMay 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for AutoimmunityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Maxima Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Amsterdam UMC, Maastricht University Medical Center
- Responsible party
- Principal investigator, Willem A.R. Zwaans, Maxima Medical Center
- Investigators
- Willem AR Zwaans, MD PhD, Principal investigator, Maxima Medical CenterMaurits JC Gielen, MD, Study director, Maxima Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06363903
- Sponsor's protocol ID
- 2022-MMC-051
- Status last verified
- Apr 2024
- First submitted
- 26 Feb 2024
- Last updated
- 12 Apr 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 18355779Lowenstein 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.
PubMed 28674735Chughtai 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.
PubMed 28034649Chughtai 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.
PubMed 28233069Kowalik 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.
PubMed 35020091Cohen 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.
PubMed 31174820Muller 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.
PubMed 34524725Zwaans 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.
PubMed 27815571Slooter 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.
PubMed 28840390
Study at a glance
From the registry record, last updated by the sponsor on 12 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Autoimmume/Inflammatory Syndrome Induced by Adjuvants (ASIA Syndrome) Caused by Polypropylene Mesh Implantation - a Pilot Study for Diagnostics and Treatment
- ClinicalTrials.gov ID
- NCT06363903
- Acronym / sponsor ID
- 2022-MMC-051
- Conditions
- Autoimmunity, Inguinal Hernia, Stress Urinary Incontinence, Pelvic Organ Prolapse, Implant Complication, Systemic Autoimmune Disease
- Keywords
- ASIA; Polypropylene; Mesh reaction; Implant; Pilot
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Maxima Medical CenterUniversity, hospital or other
- Collaborators
- Amsterdam UMC, Maastricht University Medical Center
- Study start
- 9 May 2022 (actual)
- Primary completion
- May 2024 (estimated)
- Study completion
- May 2025 (estimated)
- First posted
- 12 Apr 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Included patients | – | Diagnostic Test: mesh allergy test, Diagnostic Test: blood tests, Procedure: Mesh removalPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (4 listed)
- Known auto-immune disorders;
- Known malignancies;
- (Low grade) infections or other inflammatory diseases at time of surgery;
- Cognitively impaired individuals.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| mesh allergy testa 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. | Diagnostic test | Included patients |
| blood testsBlood tests for diagnosis of autoimmune diseases will be performed | Diagnostic test | Included patients |
| Mesh removalIf wish for mesh removal persists, this procedure can be performed after separate informed consent (within the study), as standard practice of care. | Procedure or surgery | Included patients |
Primary outcome
Positive diagnostic tests
Time frame: 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.
5 secondary outcomes
Autoimmune complaints and objective findings in immunologic blood test
Time frame: At inclusion, questionnaires repeated after 6 and 12 months. Blood tests will not be repeated after tests at inclusion.
Autoimmune complaints and objective findings in mesh allergy test (MAT)
Time frame: 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)
Mesh removal and subjective complaints
Time frame: Follow-up 1 year after surgery. At inclusion, questionnaires repeated after 6 and 12 months.
Mesh histopathology
Time frame: 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.
Patient demographics
Time frame: 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.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Apr 2024.
- Background: PubMed 18355779Denman 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.
- Background: PubMed 28674735Lowenstein 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.
- Background: PubMed 28034649Chughtai 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.
- Background: PubMed 28233069Chughtai 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.
- Background: PubMed 35020091Kowalik 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.
- Background: PubMed 31174820Cohen 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.
- Background: PubMed 34524725Muller 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.
- Background: PubMed 27815571Zwaans 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.
- Background: PubMed 28840390Slooter 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Willem AR Zwaans, MD PhD principal investigator
Maxima Medical Center
Maurits JC Gielen, MD study director
Maxima Medical Center
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Autoimmunity and Inguinal Hernia, run by Maxima Medical Center at 3 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 12 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Willem AR Zwaans, MD PhD (+31408888550, willem.zwaans@mmc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Positive diagnostic tests (time frame: At inclusion. There is no need to repeat this test after first result.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06363903, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Apr 2024; AzTrials last refreshed its copy on 4 Nov 2026.