Ignite Creation Date:
2025-12-24 @ 3:29 PM
Ignite Modification Date:
2026-01-01 @ 9:39 PM
Study NCT ID:
NCT07149792
Status:
RECRUITING
Last Update Posted:
2025-09-02
First Post:
2025-08-17
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
A Multi-center RCT Clinical Trial on Personalized Precision Medicine for Patients With Psoriasis and Psoriatic Arthritis and Investigation on Cardiovascular Biomarkers
Sponsor:
Taichung Veterans General Hospital
Organization:
Study Overview
Official Title:
A Multi-center RCT Clinical Trial on Personalized Precision Medicine for Patients With Psoriasis and Psoriatic Arthritis and Investigation on Cardiovascular Biomarkers
Status:
RECRUITING
Status Verified Date:
2025-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
SMILE
Brief Summary:
The inclusion criteria for this study were patients aged 18 to 75 years with a confirmed diagnosis of psoriasis by a dermatologist or psoriatic arthritis by a rheumatologist. Patients with active infections or suspected malignancies were excluded.
A total of 40 patients with psoriasis, with or without psoriatic arthritis, were enrolled from multiple centers in Taiwan. All participants were recruited from the outpatient clinics of either the Department of Allergy, Immunology, and Rheumatology or the Department of Dermatology in tertiary hospitals across Taiwan.
Participants were randomly assigned to one of two groups:
Prescreen Strategy-Based Biologics Selection Group
Standard-Based Biologics Selection Group
Patients will be followed up at weeks 4, 8, 12, 24, 32, 40, 48, 56, 64, and 72. Follow-up may be extended up to 3 years if necessary.
Clinical assessments will include:
Primary endpoints: PASI (Psoriasis Area and Severity Index), painful joint count, swollen joint count, and DAPSA (Disease Activity in Psoriatic Arthritis) score.
Secondary endpoints: DLQI (Dermatology Life Quality Index), BSA (Body Surface Area), pruritus score, and internal carotid artery thickness measured at 6 months, 1 year, and 2 years.
A total of 40 patients with psoriasis, with or without psoriatic arthritis, were enrolled from multiple centers in Taiwan. All participants were recruited from the outpatient clinics of either the Department of Allergy, Immunology, and Rheumatology or the Department of Dermatology in tertiary hospitals across Taiwan.
Participants were randomly assigned to one of two groups:
Prescreen Strategy-Based Biologics Selection Group
Standard-Based Biologics Selection Group
Patients will be followed up at weeks 4, 8, 12, 24, 32, 40, 48, 56, 64, and 72. Follow-up may be extended up to 3 years if necessary.
Clinical assessments will include:
Primary endpoints: PASI (Psoriasis Area and Severity Index), painful joint count, swollen joint count, and DAPSA (Disease Activity in Psoriatic Arthritis) score.
Secondary endpoints: DLQI (Dermatology Life Quality Index), BSA (Body Surface Area), pruritus score, and internal carotid artery thickness measured at 6 months, 1 year, and 2 years.
Detailed Description:
To prepare the PBMC (peripheral blood mononuclear cell) culture, 16 mL of peripheral blood is collected from each patient using sodium citrate tubes (Vacutainer CPT, BD Biosciences, Franklin Lakes, NJ, USA). PBMCs are isolated by centrifugation at 1800 × g for 20 minutes at room temperature with the brake turned off, resulting in the separation of plasma, PBMCs, gel plugs, and red blood cell (RBC) layers.
The isolated PBMCs are washed with phosphate-buffered saline (PBS) and then cultured in RPMI-1640 medium supplemented with 10% fetal bovine serum (FBS) and 1% penicillin/streptomycin at 37 °C in a 5% CO₂ incubator.
A total of 6 × 10⁵ cells/mL are seeded into 12-well plates and treated for 24 hours under the following conditions:
Control
Streptococcus pyogenes only
S. pyogenes + adalimumab (4 μg/mL)
S. pyogenes + golimumab (0.5 μg/mL)
S. pyogenes + certolizumab (20 μg/mL)
S. pyogenes + ustekinumab (0.25 μg/mL)
S. pyogenes + ixekizumab (3.5 μg/mL)
S. pyogenes + secukinumab (16.7 μg/mL or 34 μg/mL)
S. pyogenes + guselkumab (1.2 μg/mL)
S. pyogenes + risankizumab (2 μg/mL)
Culture supernatants are collected for subsequent cytokine measurement. The concentrations of biological agents used correspond to the trough serum concentrations at steady state as indicated in the pharmacokinetic sections of reference data. The two concentrations of secukinumab (16.7 μg/mL and 34 μg/mL) reflect the two common clinical doses of 150 mg and 300 mg per month, respectively.
Cytokine Analysis
Cytokine levels are measured in the collected supernatants using a protein multiplex immunoassay system (Bio-Plex Cytokine Array System, Bio-Rad Laboratories, Hercules, CA, USA). The following cytokines and chemokines are analyzed:
IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17A, IFN-γ, TNF-α, monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory proteins (MIP-1α and MIP-1β), platelet-derived growth factor-BB (PDGF-BB), and chemokine (CC motif) ligand 5 (RANTES).
Screening Method for Biologic Agents
RANTES Exclusion First, biologics that induce a RANTES level ≥1.5 times higher than that of S. pyogenes-only treatment are excluded.
Scoring System for Biologic Selection in Psoriasis
Remaining biologics are categorized into three grades based on biomarker levels:
IFN-γ
IL-17A
IFN-γ/IL-4
IFN-γ/IL-13
IL-17A/IL-4
IL-17A/IL-13
Grade 1 (Most appropriate): Lowest biomarker values
Grade 2 (Possibly appropriate): Intermediate values
Grade 3 (Not recommended): Highest values
Each grade is subdivided into a, b, and c groups:
Lower values within a grade are ranked as a, followed by b, then c
Scoring is as follows:
1. a = +3, 1b = +2, 1c = +1.5
2. a = +1, 2b = +0.5, 2c = 0
3. a = -0.5, 3b = -1, 3c = -1.5
The total score for each biologic is the sum of individual biomarker scores. Based on total scores:
High score = Most appropriate
Medium score = Possibly appropriate
Low score = Not recommended
Scoring for Psoriatic Arthritis (PsA)
For PsA, biologics are selected based on the lowest RANTES, MCP-1 and IFN-γ levels:
Grade 1 (Most appropriate): Lowest biomarker values Grade 2 (Possibly appropriate): Intermediate values Grade 3 (Not recommended): Highest values RANTES: 2+, 1+, 0 MCP-1: 1+, 0.5+, 0 IFN-γ: 1+, 0.5+, 0 The final score is the sum of RANTES MCP-1 and IFN-γ scores. Biologics with the lowest total scores are preferred.
Patient Assignment in Strategic Group
Biologics from the "most appropriate" group are selected for each patient in the strategic group. The following clinical indicators are monitored over time:
Absolute PASI
Tender joint count
Swollen joint count
DAPSA score
DLQI
Internal carotid artery intima thickness
Follow-up Timeline
Clinical assessments: Weeks 0, 2, 4, 12, 24, and 48
Intima thickness: Weeks 0 and 48
Outcome Comparison Outcomes between the strategic selection group and standard care group are compared at Weeks 24 and 48, with extended follow-up up to 5 years. Primary outcomes include PASI and DLQI scores.
Statistical Analysis
All statistical analyses are conducted using SPSS version 22 (IBM, Armonk, NY, USA). Demographic and clinical characteristics, as well as outcome measures (PASI, joint counts, DAPSA, DLQI, and carotid intima thickness), are analyzed using the Mann-Whitney U test and Spearman's rho correlation.
Data are presented as mean ± standard deviation. Two-sided p values \< 0.05 are considered statistically significant.
The isolated PBMCs are washed with phosphate-buffered saline (PBS) and then cultured in RPMI-1640 medium supplemented with 10% fetal bovine serum (FBS) and 1% penicillin/streptomycin at 37 °C in a 5% CO₂ incubator.
A total of 6 × 10⁵ cells/mL are seeded into 12-well plates and treated for 24 hours under the following conditions:
Control
Streptococcus pyogenes only
S. pyogenes + adalimumab (4 μg/mL)
S. pyogenes + golimumab (0.5 μg/mL)
S. pyogenes + certolizumab (20 μg/mL)
S. pyogenes + ustekinumab (0.25 μg/mL)
S. pyogenes + ixekizumab (3.5 μg/mL)
S. pyogenes + secukinumab (16.7 μg/mL or 34 μg/mL)
S. pyogenes + guselkumab (1.2 μg/mL)
S. pyogenes + risankizumab (2 μg/mL)
Culture supernatants are collected for subsequent cytokine measurement. The concentrations of biological agents used correspond to the trough serum concentrations at steady state as indicated in the pharmacokinetic sections of reference data. The two concentrations of secukinumab (16.7 μg/mL and 34 μg/mL) reflect the two common clinical doses of 150 mg and 300 mg per month, respectively.
Cytokine Analysis
Cytokine levels are measured in the collected supernatants using a protein multiplex immunoassay system (Bio-Plex Cytokine Array System, Bio-Rad Laboratories, Hercules, CA, USA). The following cytokines and chemokines are analyzed:
IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17A, IFN-γ, TNF-α, monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory proteins (MIP-1α and MIP-1β), platelet-derived growth factor-BB (PDGF-BB), and chemokine (CC motif) ligand 5 (RANTES).
Screening Method for Biologic Agents
RANTES Exclusion First, biologics that induce a RANTES level ≥1.5 times higher than that of S. pyogenes-only treatment are excluded.
Scoring System for Biologic Selection in Psoriasis
Remaining biologics are categorized into three grades based on biomarker levels:
IFN-γ
IL-17A
IFN-γ/IL-4
IFN-γ/IL-13
IL-17A/IL-4
IL-17A/IL-13
Grade 1 (Most appropriate): Lowest biomarker values
Grade 2 (Possibly appropriate): Intermediate values
Grade 3 (Not recommended): Highest values
Each grade is subdivided into a, b, and c groups:
Lower values within a grade are ranked as a, followed by b, then c
Scoring is as follows:
1. a = +3, 1b = +2, 1c = +1.5
2. a = +1, 2b = +0.5, 2c = 0
3. a = -0.5, 3b = -1, 3c = -1.5
The total score for each biologic is the sum of individual biomarker scores. Based on total scores:
High score = Most appropriate
Medium score = Possibly appropriate
Low score = Not recommended
Scoring for Psoriatic Arthritis (PsA)
For PsA, biologics are selected based on the lowest RANTES, MCP-1 and IFN-γ levels:
Grade 1 (Most appropriate): Lowest biomarker values Grade 2 (Possibly appropriate): Intermediate values Grade 3 (Not recommended): Highest values RANTES: 2+, 1+, 0 MCP-1: 1+, 0.5+, 0 IFN-γ: 1+, 0.5+, 0 The final score is the sum of RANTES MCP-1 and IFN-γ scores. Biologics with the lowest total scores are preferred.
Patient Assignment in Strategic Group
Biologics from the "most appropriate" group are selected for each patient in the strategic group. The following clinical indicators are monitored over time:
Absolute PASI
Tender joint count
Swollen joint count
DAPSA score
DLQI
Internal carotid artery intima thickness
Follow-up Timeline
Clinical assessments: Weeks 0, 2, 4, 12, 24, and 48
Intima thickness: Weeks 0 and 48
Outcome Comparison Outcomes between the strategic selection group and standard care group are compared at Weeks 24 and 48, with extended follow-up up to 5 years. Primary outcomes include PASI and DLQI scores.
Statistical Analysis
All statistical analyses are conducted using SPSS version 22 (IBM, Armonk, NY, USA). Demographic and clinical characteristics, as well as outcome measures (PASI, joint counts, DAPSA, DLQI, and carotid intima thickness), are analyzed using the Mann-Whitney U test and Spearman's rho correlation.
Data are presented as mean ± standard deviation. Two-sided p values \< 0.05 are considered statistically significant.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
True
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| TCVGH-1445602C | OTHER_GRANT | TAICHUNG VETERANS GENERAL HOSPITAL | View |