Clinical trial NCT06778343: Biomarkers in Inflammatory Rheumatic Diseases Diagnosis
Official title: BIRDD: Biomarkers in Inflammatory Rheumatic Diseases Diagnosis - Ankylosing Spondylitis, Rheumatoid Arthritis and Systemic Lupus Erythematosus
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Ankylosing Spondylitis
Rheumatic Arthritis
Systemic Lupus Erythematosus
Keywords: Biomarker
Diagnosis
Lead sponsor: Universidade Nova de Lisboa
Sponsor class: OTHER
Collaborators: name: Centro Hospitalar Lisboa Ocidental Hospital Egas Moniz
First posted: 2025-01-16
Enrollment: 134
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: People that satisfy the eligibity criteria with AS, RA, SLE and healthy individuals (as controls) currently living in Portugal.

Brief summary: Ankylosing spondylitis (AS), Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE) are three diseases where early diagnosis remains a major challenge. However, early diagnosis is the main determinant for a better prognosis. In the early stage, symptoms may be nonspecific and often difficult to establish a differential diagnosis between rheumatic diseases and other diseases, namely infectious and cancer diseases.

Detailed description: The management of these diseases has undergone major advances in recent years, both in terms of the drugs armamentarium and therapeutic strategy. Treating disease to target, aiming at remission, through a tight control protocol is regarded as the standard of care. These principles were imported from RA and became the main strategy to approach several rheumatic inflammatory diseases. Reaching clinical and radiographic disease remission has therefore become an achievable goal. Increasing evidence has demonstrated that early diagnosis, prompt treatment initiation and early achievement of remission are the major predictors of good long-term clinical, functional and radiographic outcomes. The main reason for diagnostic delays is that classification criteria sets, including, imaging or biochemical changes, require time to occur. Rheumatoid factor, anti-CCP, ANA, anti-DNA and anti-Sm autoantibodies are often negative in the early stages of the disease; HLA B27 gene has a low specificity for AS. New criteria are now available and some biomarkers are emerging that allow earlier patient diagnosis. This new paradigm, needs new research trying to identify the most reliable biomarkers with relevance for clinical use.

The investigators intend to analyse biological samples, peripheral blood, from patients with well-established diagnosis (34 AS, 34 RA and 34 SLE) and 34 healthy controls (crossed by gender and age). Laboratory analysis will be based on transcriptomic approach trying to put in evidence specific biomarkers for each disease. The method is based on a analytical methodology already proven with success in stratifying patients.

The main objective of this study will be the development of a diagnostic chip to be implemented in clinical practice. The results should be confirmed in the same set of patients using quantitative real-time protein chain reaction (RT-PCR) and the validation in a new set of patients. The main objective of this project is to establish a quick method to stratify patients of the three diseases- AS, SLE, RA.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of AS, RA, SLE according the mentioned criteria;
* Ability to provide informed consent;
* If entering the study on NSAIDs, tramadol, combination of paracetamol and codeine or hydrocodone, and/or non-opioid analgesics, subject must be on stable dose(s) for at least 14 days prior to the screening visit;
* If entering the study on oral corticosteroids, subject must be on a stable dose of prednisone (≤ 10 mg/day), or oral corticosteroid equivalents, for at least 14 days prior to the screening visit;
* If entering the study on MTX, leflunomide, SSZ, and/or hydroxychloroquine, subject must be on a stable dose of MTX (≤ 25 mg/week) and/or SSZ (≤ 3 g/day) and/or hydroxychloroquine (≤ 400 mg/day) or leflunomide (≤ 20 mg/day) for at least 28 days prior to the screening visit. A combination of up to two background csDMARDs is allowed;
* Subject is judged to be in good health as determined by the Principal Investigator based upon the results of medical history, laboratory profile, physical examination, x-Ray performed at the Screening Visit.

Exclusion Criteria:

* Current pregnancy or breastfeeding;
* Prior exposure to any biologic therapy;
* Intra-articular joint or tendon sheaths injections, spinal/paraspinal injection(s), or parenteral administration of corticosteroids within 28 days prior to the Baseline Visit. Inhaled or topical corticosteroids are allowed;
* Receipt of any live vaccine within 4 weeks prior to the screening visit;
* History of clinically significant (per Investigator\&#39;s judgment) drug or alcohol abuse within the last 6 months;
* Subject has a history of inflammatory arthritis of different etiology other than AS, RA or SLE (including but not limited to PsA, mixed connective tissue disease, reactive arthritis, scleroderma, polymyositis, dermatomyositis, fibromyalgia), or any arthritis with onset prior to 17 years of age;
* Any uncontrolled medical condition (e.g., uncontrolled diabetes mellitus, unstable ischemic heart disease);
* History of any malignancy;
* Positive serology for hepatitis B, hepatitis C, or human immunodeficiency virus;
* Infections requiring hospitalization or intravenous treatment with antibiotics within 30 days or oral treatment with antibiotics within 14 days before enrollment;
* Note : Healthy Controls should be matched by gender and age. People with acute infections or injuries (in the last 6 months) or non-controlled chronic diseases (cardiac, metabolic, lung, neurologic, gastro-intestinal or renal) will be exclude. Family history of Auto-Immune diseases as diagnosed by a rheumatologist will be also excluded.

Primary outcomes:
measure: Identify a transcriptomic signature to optimize patient stratification (between AS, RA and SLE)
timeFrame: From enrollment to the end of the study at 12 weeks.
Secondary outcomes:
measure: Identify novel signaling pathways that may represent new therapeutic targets
timeFrame: From enrollment to the end of the study at 12 weeks.
measure: Compare transcriptomic signatures in different levels of disease activity
timeFrame: From enrollment to the end of the study at 12 weeks
Other outcomes:
Locations:
city: Lisboa
country: Portugal
facility: ULS Lisboa Ocidental, Hospital de Egas Moniz
Study officials:
References:
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