Relationship Between Immunosuppressive Treatment Status and Clinical Course of Parkinson's Disease

Official title

Analysis of the Relationship Between Immunosuppressive Treatment Status and Clinical Course of Parkinson's Disease

Overview

The goal of this observational study is to learn if immunosuppressive drug treatment influences the clinical course of Parkinson's disease. Recent research suggests that Parkinson's disease may have an inflammatory background. Numerous studies have identified elevated levels of pro-inflammatory markers in people with Parkinson's disease. Therefore, immunosuppressive drugs may potentially affect the course of this disease. The investigators will recruit people with Parkinson's disease, who receive long-term immunosuppressive treatment for other chronic illnesses, into the study group. The study will also recruit people with Parkinson's disease with no history of immunosuppressive drug treatment into the control group. The main question this study aims to answer is: \> Does immunosuppressive drug treatment slow down the onset and/or progression of Parkinson's disease? Researchers will compare Parkinson's disease progression rates and serum inflammatory marker levels between the study and control group, to see if immunosuppressive drug treatment influences the course of Parkinson's disease. The study requires each participant to attend one hospital appointment. This appointment will be approximately one hour long, and will involve: 1. clinical Parkinson's disease motor assessments conducted by the research team -\> participants will be evaluated in the OFF state, meaning they will not have taken their Parkinson's disease medication the day of the assessment; 2. completion of Parkinson's disease symptom scales; 3. a one-time serum sample collection; 4. detailed medical history obtainment from the participant by the research team, with a primary focus on the patient's immunosuppressive treatment history and individual clinical course of Parkinson's disease.

Primary outcome measures

• Annual motor progression rate - Unified Parkinson's Disease Rating Scale PART III OFF [Time frame: Day 1]
• Annual LEDD increase rate [Time frame: Day 1]
• Age of motor symptom onset [Time frame: Day 1]

Secondary outcome measures (6)

• Annual motor progression rate - Hoehn and Yahr scale [Time frame: Day 1]
• Annual motor progression rate - Unified Parkinson's Disease Rating Scale PART II [Time frame: Day 1]
• Serum inflammatory marker levels - IL-1β [Time frame: Day 1]
• Serum inflammatory marker levels - IL-6 [Time frame: Day 1]
• Serum inflammatory marker levels - calprotectin [Time frame: Day 1]
• Serum inflammatory marker levels - TNFα [Time frame: Day 1]

Eligibility criteria

Inclusion criteria for the study group:

• Diagnosis of Parkinson's disease according to the International Parkinson and Movement Disorder Society Clinical Diagnostic Criteria for Parkinson's disease;
• Immunosuppressive medication use - medication taken regularly, which we have defined as administered at a dose and frequency effective for the indicated disease, for over 12 months, systemic administration route (oral, intramuscular, subcutaneous, intravenous and inhaled); The most commonly used immunosuppressive drugs that we anticipate will be used by the study group participants include: glucocorticosteroids (GC) - budesonide, cortisone, dexamethasone, hydrocortisone, methylprednisolone, prednisolone, prednisone, triamcinolone; calcineurin inhibitors - tacrolimus, cyclosporine; inosine monophosphate dehydrogenase (IMDH) inhibitors - azathioprine, leflunomide, mycophenolate; mammalian target of rapamycin (mTOR) inhibitors - sirolimus, everolimus; biologics - abatacept, adalimumab, anakinra, certolizumab, etanercept, infliximab, ixekizumab, natalizumab, rituximab, secukinumab, tocilizumab, ustekinumab, vedolizumab; antimetabolites - methotrexate; inclusion of participants taking immunosuppressive drugs not listed above will be considered individually;
• Provision of informed consent to participate in the study.

Inclusion criteria for the control group:

• Diagnosis of Parkinson's disease according to the International Parkinson and Movement Disorder Society Clinical Diagnostic Criteria for Parkinson's Disease;
• No history of regular use of immunosuppressive medications;
• Provision of informed consent to participate in the study.

Exclusion criteria for the study group:

• Immunosuppressive drug administration at an ad hoc basis (i.e. when symptoms occur) or irregularly (i.e. drug taken at an inappropriate dose and/or with a regularity ineffective for the indicated disease);
• Use of immunosuppressive drugs for a period of less than 12 months;
• Ineffective treatment of the disease requiring the use of immunosuppressive drugs (no improvement/progression of disease symptoms);

Additional exclusion criteria for both the study and control groups:

• Advanced cancer; severe heart failure; severe renal failure; untreated autoimmune disease; active inflammation; diseases that impair drug absorption/metabolism;
• Dementia;
• Failure/inability to provide informed consent.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Poland · 1 center

• Department of Neurology, Faculty of Health Science, Medical University of Warsaw — Warsaw

Publications

• Brumm MC, Siderowf A, Simuni T, Burghardt E, Choi SH, Caspell-Garcia C, Chahine LM, Mollenhauer B, Foroud T, Galasko D, Merchant K, Arnedo V, Hutten SJ, O'Grady AN, Poston KL, Tanner CM, Weintraub D, Kieburtz K, Marek K, Coffey CS; Parkinson's Progression Markers Initiative. Parkinson's Progression Markers Initiative: A Milestone-Based Strategy to Monitor Parkinson's Disease Progression. J Parkins PMID 37458046
• Postuma RB, Berg D, Stern M, Poewe W, Olanow CW, Oertel W, Obeso J, Marek K, Litvan I, Lang AE, Halliday G, Goetz CG, Gasser T, Dubois B, Chan P, Bloem BR, Adler CH, Deuschl G. MDS clinical diagnostic criteria for Parkinson's disease. Mov Disord. 2015 Oct;30(12):1591-601. doi: 10.1002/mds.26424. PMID 26474316
• Dulski J, Heckman MG, Nowak JM, Wszolek ZK. Protective Effect of Glucocorticoids against Symptomatic Disease in CSF1R Variant Carriers. Mov Disord. 2023 Aug;38(8):1545-1549. doi: 10.1002/mds.29504. Epub 2023 Jun 13. PMID 37309919
• Racette BA, Gross A, Vouri SM, Camacho-Soto A, Willis AW, Searles Nielsen S. Immunosuppressants and risk of Parkinson disease. Ann Clin Transl Neurol. 2018 May 31;5(7):870-875. doi: 10.1002/acn3.580. eCollection 2018 Jul. PMID 30009205
• Bruggeman A, Vandendriessche C, Hamerlinck H, De Looze D, Tate DJ, Vuylsteke M, De Commer L, Devolder L, Raes J, Verhasselt B, Laukens D, Vandenbroucke RE, Santens P. Safety and efficacy of faecal microbiota transplantation in patients with mild to moderate Parkinson's disease (GUT-PARFECT): a double-blind, placebo-controlled, randomised, phase 2 trial. EClinicalMedicine. 2024 Mar 27;71:102563. do PMID 38686220
• Schwiertz A, Spiegel J, Dillmann U, Grundmann D, Burmann J, Fassbender K, Schafer KH, Unger MM. Fecal markers of intestinal inflammation and intestinal permeability are elevated in Parkinson's disease. Parkinsonism Relat Disord. 2018 May;50:104-107. doi: 10.1016/j.parkreldis.2018.02.022. Epub 2018 Feb 12. PMID 29454662
• Franceschi C, Valensin S, Fagnoni F, Barbi C, Bonafe M. Biomarkers of immunosenescence within an evolutionary perspective: the challenge of heterogeneity and the role of antigenic load. Exp Gerontol. 1999 Dec;34(8):911-21. doi: 10.1016/s0531-5565(99)00068-6. PMID 10673145
• Qin XY, Zhang SP, Cao C, Loh YP, Cheng Y. Aberrations in Peripheral Inflammatory Cytokine Levels in Parkinson Disease: A Systematic Review and Meta-analysis. JAMA Neurol. 2016 Nov 1;73(11):1316-1324. doi: 10.1001/jamaneurol.2016.2742. PMID 27668667

Identifiers

NCT: NCT06834191 · KB/164/2024

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗