Cytokines and Vascular Inflammation in Psoriasis

Correlation Between Serum Levels of Cytokines and a Chemokine and Vascular Inflammation in Patients With Moderate to Severe Psoriasis

Psoriasis is an inflammatory disease involving the skin, the joints and the vascular compartment. The mechanisms linking inflammation in the skin and joints and in the vascular walls are poorly understood. One hypothesis for the increase in vascular inflammation observed in patients with psoriasis involves circulating pro-inflammatory cytokines. Patients with psoriasis have an increase in serum levels of tumor necrosis factor alpha (TNF-alpha), Interleukin-17 (IL-17), IL-22, IL-6 as well as a the chemokine S100A913. It is possible that one of those cytokines/chemokine induces vascular inflammation in the vascular compartment. The purpose of this cross sectional retrospective study is to highlight the correlation between vascular wall inflammation using 18F-2-fluoro-2-deoxy-D-glucose - Positron Emission Tomography (FDG-PET) fluorodeoxyglucose technology and pro-inflammatory cytokines/chemokine.

Study Overview

• Status: Completed
• Conditions: Psoriasis; Coronary Atherosclerosis; Vascular Inflammation

Detailed Description

Baseline frozen serum samples will be identified from the 107 enrolled Inno-6025 (Abbvie A13-935) (ClinicalTrials.gov Identifier NCT01722214) patients who also underwent a pre-adalimumab FDG-PET scan for the study. Serum cytokine and chemokine levels in these samples will be measured; IL-17 and IL-22 using the Singulex immunoassay platform, and S100A9, IL-6 and TNF alpha using multiplex ELISA. Vascular inflammation will be measured as the target to background ratio (TBR) in the ascending aorta using PET-scan technology. Correlation analyses will be performed between serum levels of cytokines and a chemokine and vascular inflammation.

• Study Type: Observational
• Enrollment (Actual): 96

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Markham, Ontario, Canada, L3P 1X2
      • Lynderm Research
    • Windsor, Ontario, Canada, N8W 5L7
      • Windsor Clinical Research Inc.
  • Quebec
    • Drummondville, Quebec, Canada, J2B 5L4
      • Clinique Dre Isabelle Delorme
    • Montreal, Quebec, Canada, H2K 4L5
      • Innovaderm Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Subjects previously enrolled in the Inno-6025 Trial (ClinicalTrials.gov Identifier NCT01722214)

Description

Inclusion Criteria:

1. Patient has plaque psoriasis.
2. Patient has at least a 6 month history of plaque psoriasis.
3. Patient has a Body Surface Area (BSA) covered with psoriasis of 5% or more at Day 0.
4. Patient is a candidate for systemic therapy.
5. Patient is male or female, 18 to 80 years of age at time of consent.
6. Patient's weight at screening is a maximum of 180 kg.
7. Patient using medication to control angina, hypertension, serum lipids and any medication that can have an effect on inflammation must be on a stable dose for at least 8 weeks before Day 0.
8. Patient has an ascending aorta atherosclerotic plaque inflammation target-to-background ratio of 1.6 or more as determined by 18-FDG uptake measured by PET scanning.

9. Patient or patient's partner has been in a menopausal state for at least a year, is surgically sterile (hysterectomy, bilateral oophorectomy, tubal ligation or vasectomy), is clinically diagnosed infertile, has a same-sex partner, is abstinent, or is willing to use effective contraceptive method for at least 30 days before Day 0 and at least 6 months after the last study drug administration. Effective contraceptive methods are:

   1. Barrier methods such as condom, sponge or diaphragm combined with spermicide in foam, gel or cream;
   2. Hormonal contraception (oral, intramuscular, implant or transdermal) which include Depo-Provera, Evra and Nuvaring;
   3. Intrauterine device (IUD);
10. Female patients of childbearing potential must have a negative serum pregnancy test at the Screening visit.
11. Patient is judged to be in good general health as determined by the principal investigator based upon the results of medical history, laboratory profile, physical examination, and Chest X-Ray (CXR) performed at Screening.
12. Patient will be evaluated for latent TB infection with a purified protein derivative (PPD) or a Quantiferon Gold test and CXR. Patient who demonstrates evidence of latent TB infection (either PPD more than or equal to 5 mm of induration or positive Quantiferon Gold, irrespective of Bacillus Calmette-Guerin (BCG) vaccination status and negative CXR findings for active TB, and/or suspicious CXR findings) will not be allowed to participate in the study.
13. Patient must be able and willing to provide written informed consent and comply with the requirements of this study protocol.
14. Patient must be able and willing to self-administer subcutaneous (SC) injections or have a qualified person available to administer SC injections.

Exclusion Criteria:

1. Patient has spontaneously improving or rapidly deteriorating plaque psoriasis.
2. Patient has other active infections (bacterial, fungal or viral) or skin diseases or skin infections (bacterial, fungal, or viral) that may interfere with evaluation of psoriasis or with patient's safety.
3. Patient has a history of an allergic reaction or significant sensitivity to constituents of study drug, including latex (a component of the pre-filled syringe).
4. Patient has used a non-biological systemic therapy for the treatment of psoriasis less than 30 days before Day 0.
5. Patient has used an investigational chemical or biological agent less than 30 days or 5 half-lives prior to the Day 0 visit (whichever is longer).
6. Patient has used a biological therapy for the treatment of psoriasis less than 90 days before day 0.
7. Patient has used a systemic immunosuppressor (eg. Azathioprine, 6-mercaptopurine) less than 30 days before Day 0.
8. Patient is taking or requires oral or injectable corticosteroids during the study. Inhaled corticosteroids for stable medical conditions are allowed.
9. Patient has used a topical treatment for psoriasis or has used phototherapy within the last 2 weeks prior to Day 0 (at the exception of low potency topical corticosteroids for groin, genitals, face, inframammary area, palms and soles).
10. Patient has received Anakinra/Kineret within the last 2 weeks prior to the Day 0 visit or is likely to receive Anakinra/Kineret during the course of the study
11. Patient has a poorly controlled medical condition, such as uncontrolled diabetes, documented history of recurrent infections, unstable ischemic heart disease, class III or IV (New York Heart Association Functional Classification; NYHA) congestive heart failure, an ejection fraction of less than 30%, recent stroke (within the past 3 months), chronic leg ulcer or any other condition which, in the opinion of the investigator, would put the patient at risk if participating in the study.
12. Patient has had a myocardial infarction or has been hospitalized for a cardiac condition within the past 12 weeks.
13. Patient has a history of acute coronary syndrome, percutaneous coronary intervention, coronary artery bypass graft, carotid endarterectomy, stent installation or carotid revascularization within 12 weeks of Day 0.
14. Patient has had a percutaneous coronary intervention in the past 12 months.
15. Patient plans for a change in medical treatment for angina, serum lipids, hypertension or any other medication that can have a significant effect on inflammation during the course of the study.
16. Patient has history of neurologic symptoms suggestive of central nervous system (CNS) demyelinating disease (e.g. optic neuritis, visual disturbance, gait disorder/ataxia, facial paresis, apraxia).
17. Patient has history of cancer or lymphoproliferative disease other than a successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma and/or localized carcinoma in situ of the cervix.
18. Patient has a history of listeriosis, treated or untreated Tuberculosis (TB), persistent chronic infections, or recent active infections requiring hospitalization or treatment with intravenous anti-infectives within 30 days prior to the Day 0 visit or oral anti-infectives within 14 days prior to the Day 0 visit.
19. Patient has received a live attenuated vaccine 28 days or less before Day 0 or plan to receive a live attenuated vaccine during the study and up to 4 months after the last study drug administration..
20. Patient with hepatitis B or hepatitis C viral infection
21. Patient with any of the following: hemoglobin ≤ 10 g/L, white blood cell count ≤ 3.0 X 109/L, platelet count ≤130 X 10^9/L, alanine transaminase (ALT) ≥ 2 times the upper limit of normal, aspartate transaminase (AST) ≥ 3 times the upper normal limit, total bilirubin ≥ 2 times the upper normal limit or creatinine ≥ 150 µmol/L.
22. Patient currently uses or plans to use anti-retroviral therapy at any time during the study.
23. Patient is known to have immune deficiency or is immunocompromised.
24. Female patient who is pregnant or breast-feeding or considering becoming pregnant during the study or for 6 months after the last dose of study medication.
25. Patient has a history of clinically significant drug or alcohol abuse in the last year.
26. Patient who plans to travel in an area where tuberculosis is endemic during the study and up to 4 months after the last study drug administration.
27. Patient is considered by the investigator, for any reason, to be an unsuitable candidate for the study.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Frozen serum; The cohort consists of original subjects from the Inno-6025 Trial who previously consented to measuring protein in the blood involved in skin inflammation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between serum cytokine levels (pg/mL) and TBR in the ascending aorta.	Correlation between serum levels of various cytokines including TNF alpha, IL-17, IL-22 and IL-6 and vascular inflammation measured as TBR using FDG-PET in patients with moderate to severe psoriasis	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between a serum chemokine (S100A9 (pg/mL)) levels and TBR in the ascending aorta.	Correlation between serum levels of a chemokine (S100A9) and vascular inflammation measured as TBR using FDG-PET in patients with moderate to severe psoriasis	Baseline

Collaborators and Investigators

• Sponsor: Innovaderm Research Inc.
• Collaborators: AbbVie

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: October 31, 2014
• First Submitted That Met QC Criteria: November 28, 2014
• First Posted (Estimate): December 3, 2014

Study Record Updates

• Last Update Posted (Estimate): December 3, 2014
• Last Update Submitted That Met QC Criteria: November 28, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Keywords: PET scan; Psoriasis; Cytokine; Vascular Inflammation; Coronary Atherosclerosis; Chemokine; Ascending aorta
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Skin Diseases, Papulosquamous; Coronary Disease; Coronary Artery Disease; Myocardial Ischemia; Inflammation; Psoriasis; Atherosclerosis
• Other Study ID Numbers: Inno-6037