Baricitinib in CPPD - the BAPTIST Study

ConditionsCalcium Pyrophosphate Deposition Disease Chondrocalcinosis

Trial statusNot yet recruiting

Trial phasePhase 2

Trial typeInterventional

Biological sexAll

Age55+

SponsorI.R.C.C.S Ospedale Galeazzi-Sant'Ambrogio

About this trial

The aim of this clinical trial is to determine if baricitinib is effective in treating calcium pyrophosphate deposition disease (CPPD) in adults. The primary objective is to assess its impact on joint inflammation. The key questions the study seeks to answer are:

* Can baricitinib reduce inflammation in affected joints? * Will baricitinib lead to changes in ultrasound findings, such as calcium crystal deposition and synovitis?

Researchers will compare baricitinib to other treatments, including methylprednisolone, colchicine, hydroxychloroquine, and methotrexate with folic acid, for managing CPPD.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Signed Informed Consent;

Male and female patients aged ≥55 years;

Patients that according to the investigator's judgement will benefit from the proposed treatments (favourable benefit/risk profile)

Menopause for women;(no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However in the absence of 12 months of amenorrhea, a high follicle stimulating single measurement is insufficient.);

Disqualifiers

Patients positive at anticitrullinated positive antibodies (ACPA), any titre;

Patients affected by seronegative arthritis or other conditions that may be responsible of arthritis (i.e. gout, rheumatic polymyalgia, etc);

Patients that refuse synovial biopsy or present contraindications, according to investigator's judgement, including (but not limited to) increased risk for bleeding (platelet count &lt;100000 or use of anticoagulants), allergy to local anesthetics, suspicion of septic arthritis;

Patients with history of malignancy or lymphoproliferative disease; or have signs or symptoms suggestive of possible lymphoproliferative disease, including lymphadenopathy or splenomegaly; or have active primary or recurrent malignant disease; or have been in remission from clinically significant malignancy for &lt; 5 years;

Trial design

Design model

Parallel

Treatments tested in this trial

Baricitinib 4 MG Oral Tablet
Drug
Baricitinib is a JAK1/JAK2 inhibitor approved for use in Rheumatoid Arthritis. It is under investigation for use in several inflammatory diseases, including Psoriasis and Psoriatic Arthritis, Atopic Dermatitis, Inflammatory Bowel Disease and Systemic Lupus Erythematosus, with encouraging results. As IL-6 plays a central role in CPPD inflammatory process, a broad spectrum of interleukins and other proinflammatory proteins (including interferons) could be involved. A drug that acts by blocking more than one proinflammatory cytokine could be a promising treatment for a multifaceted disease such as CPPD.
Methylprednisolone (Corticosteroid)
Drug
The initial dosage of methylprednisolone may vary depending on the entity of inflammation and the patient's comorbidities. Usually in CPPD a short-term administration of methylprednisolone starts with 16 mg per day after breakfast decreasing the initial dosage in small decrements at appropriate time intervals until discontinuation, in about 2 weeks. Methylprednisolone will be given in combination with gastroprotective agents such as proton pump inhibitors.
Colchicine 1 MG Oral Tablet
Drug
1 or ½ tablet (depending on individual tolerance) daily after breakfast
Hydroxychloroquine 200 mg
Drug
1 tablet daily after lunch
Methotrexate + Folic Acid
Combination product
MTX 2.5 mg tablets, from 2 to 4 tablets (5-10mg), depending on disease severity, to be administered once weekly after dinner, always in the same day of the week. One tablet of folic acid (folina 5 mg) will be administered the day after MTX administration, after breakfast, to reduce and prevent the common side effects of MTX.

Treatment groups

32 Participants

are divided into 2 treatment groups

Group A: One group will receive baricitinib at the dose of 4mg/dailyActive comparator 1 intervention

Group B: standard of care (to be decided according to the guidelines)Sham comparator 4 interventions

Trial outcomes

Primary outcomes

The evaluation the effect of baricitinib on inflammation of the synovial membrane in CPPD

CD68 score will be used as outcome measure for the primary objective. CD68 score will be calculated from an analysis of 6 images from each biopsy section and expressed as the mean area of tissue occupied by positively stained cells.

Time frame

The outcome for the primary objective is the changes in the synovial tissue CD68 scoring at 12 weeks, an objective outcome measure.

Secondary outcomes

To assess the changes in Krenn synovitis score at the synovial level

Krenn score will be used to determine the degree of synovitis according to the three synovial membrane features: synovial lining cell layer, stroma cell density, and inflammatory infiltrate. All parameters will be graded with a semiquantitative score (from 0 to 3) as follows: 0 (absent), 1 (slight), 2 (moderate) and 3 (strongly positive). All parameters will be summarized with a final total score by adding the score of the single features (will range from 0 to 9) and interpreted as follows: 0-1: no synovitis; 2-4: low-grade synovitis; 5-9: high- grade synovitis.

Time frame

12 weeks

To assess the changes in cytochin levels at the synovial membrane

The biopsy samples will be immediately placed in 10% neutral buffered formalin fixed for 48 h and embedded in paraffin for histologic and immunohistochemical analyses. Overall staining intensity will be evaluated. The overall score of the staining intensity will be graded in a four degree scale: negative (0), weak (1), moderate (2), and strong (3).

Time frame

12 weeks

To determine changes at ultrasound examination in terms of calcium crystal deposition

The ultrasound assessment will include the wrists and hands, knees and the affected joints if different than hands/wrists/knees. For CPP deposition, the CPP deposits of knees, wrists and any involved site will be scored with a semi-quantitive score (0-3).

Time frame

4, 12 and 24 weeks

To determine changes at ultrasound examination in terms of synovitis

The ultrasound assessment will include the wrists, hands, knees and the affected joints if different than hands/wrists/knees. Synovitis will be scored according to the semiquantitative Global OMERACT EULAR Scoring System (GLOESS), a semiquantitative score (0-3) that can be interpreted as: no inflammation (0), slight inflammation (1), moderate inflammation (2) and severe inflammation (3)

Time frame

4, 12 and 24 weeks

Other outcomes

To explore the possible baricitinib-induced impact on whole-body metabolism

Untargeted metabolomics analysis on the same samples will be performed using standardized bioinformatics tools to discover the most relevant metabolic pathways involved in the pathogenesis of CPPD and/or valuable to monitor the therapeutic path of the CPPD patient. Targeted metabolomics will be done to quantify key small molecules involved in the energy cycles and oxidative stress. In this analysis, the metabolites will be extracted from the serum and then their concentrations will be compared to the analytical standards.

Time frame

24 weeks

Sponsors and contacts

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I.R.C.C.S Ospedale Galeazzi-Sant'Ambrogio

Lead sponsor

Source ClinicalTrials.gov

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