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Effects of Treatment With Biological Agents on Vascular and Cardiac Function in Psoriasis

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ClinicalTrials.gov Identifier: NCT02144857
Recruitment Status : Recruiting
First Posted : May 22, 2014
Last Update Posted : December 28, 2018
Sponsor:
Information provided by (Responsible Party):
Ignatios Ikonomidis, University of Athens

Brief Summary:
Psoriasis has been associated with an increasing risk for atherosclerosis. The investigators investigated whether surrogate markers of subclinical atherosclerosis, vascular dysfunction and myocardial dysfunction are impaired in patients with psoriasis compared to normal controls ,coronary artery disease patients and untreated hypertension subjects. The investigators also examined the effect of treatment with biological vs no biological agents on vascular and LV function in psoriasis.

Condition or disease Intervention/treatment Phase
Psoriasis Drug: etanercept Drug: ustekinumab Drug: cyclosporine Drug: Secukinumab Drug: Apremilast Phase 4

Detailed Description:

The investigators will compare patients with psoriasis with age and sex matched normal controls as well as patients with angiographically documented CAD and patients with untreated hypertension (HYP) used as positive control groups

Patients with psoriasis (PS) will be randomized to receive an anti-tumor necrosis-a (TNF-a) ,an anti- interleukin 12/23 regimen, an interleukin 17A antagonist, apremilast (inhibitor of phosphodiesterase-4) or a cyclosporine regimen.

The anti-TNF-agent, Etanercept will be given at a dose 50mg twice weekly for 12 weeks and after then once weekly.

The anti-IL12/23 regimen, Ustekinumab will be given at a dose 45 mg at the first visit, at 4 weeks and every 12 weeks if body weight is up to 90 kgr. For body weight >90kgr dose will be adjusted accordingly.

The IL-17A antagonist regimen namely secukinumab 300 mg SC at weeks 0, 1, 2, 3, and 4 and 300 mg SC once monthly afterwards Apremilast will be given at a dose of 30mg orally twice daily Cyclosporine will be administered at a dose 2.5-3mg/kgr daily.

At baseline , after 12 weeks and one year of treatment, the investigators will measure:

  1. pulse wave velocity (PWVc) augmentation index (AI) central systolic blood pressure (cSBP) (Complior, Alam Medical and Arteriograph,TensioMed)
  2. flow-mediated dilation of the brachial artery (FMD)
  3. carotid intima-media thickness (IMT) by ultrasonography
  4. coronary flow reserve of the LAD (CFR) by Doppler echocardiography
  5. E'/A of mitral annular velocities ,LV longitudinal (GLS -%),strain, and strain rate (LongSr-l/s), peak twisting (Tw -deg),peak twisting (Tw-deg/sec)velocity,untwisting at mitral valve opening (unTw) and untwisting (unTw) velocity using speckle tracking echocardiography .
  6. Perfused boundary region (PBR)of the sublingual arterial microvessels (ranged from 5-25 microns) using Sideview Darkfield imaging. (Microscan, Glycocheck) .The PBR in microvessels is the cell-poor layer which results from the phase separation between the flowing red blood cells (RBC) and plasma.The PBR includes the most luminal part of glycocalyx that does allow cell penetration. Increased PBR is considered an accurate index of reduced endothelial glycocalyx thickness because of a deeper RBC penetration in the glycocalyx.
  7. Fetuin serum levels, markers of oxidative stress such as malondialdehyde (MDA) serum levels, protein carbonyls aw well as thrombosis and inflammation biomarkers

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Investigator)
Primary Purpose: Treatment
Official Title: Effects of Treatment With Biological Agents on Endothelial Glycocalyx,Arterial Elastic Properties, Coronary Flow, Myocardial Deformation and Twisting in Psoriasis. Comparative Study With Patients With CAD or Untreated Hypertension.
Study Start Date : January 2013
Estimated Primary Completion Date : July 2019
Estimated Study Completion Date : July 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Psoriasis

Arm Intervention/treatment
Active Comparator: Anti-TNFa regimen
Etanercept 50 mg
Drug: etanercept
50 mg
Other Name: Enbrel

Active Comparator: Anti IL12/23 regimen
ustekinumab 45 mg
Drug: ustekinumab
45 mg
Other Name: Stelara

Active Comparator: Cyclosporine regimen
Cyclosporine 2.5-3 mg/kg
Drug: cyclosporine
Cyclosporine 2.5-3 mg/kgr
Other Name: Neoral

Active Comparator: anti-interleukin 17 A regimen
secukinumab 300 mg
Drug: Secukinumab
300 mg
Other Name: Cosentyx

Active Comparator: inhibitor of phosphodiesterase-4
apremilast 30mg
Drug: Apremilast
30mg
Other Name: Otezla




Primary Outcome Measures :
  1. Comparison of effect (improvement or deterioration) of treatment with biological vs. non biological agents on endothelial function in psoriasis [ Time Frame: 12 weeks ]
    Comparison of effect (improvement or deterioration) of treatment with biological agents (anti-tumor necrosis factor-a, anti-interleukin 12/23, anti-interleukin 17A, or apremilast regimen) with the effects of cyclosporine on endothelial function as assessed by flow mediated dilatation of the brachial artery, coronary flow reserve and endothelial glycocalyx thickness

  2. Comparison of effect (improvement or deterioration) of treatment with biological vs. non biological agents on vascular function in psoriasis [ Time Frame: 12 weeks ]
    Comparison of effect (improvement or deterioration) of treatment with biological agents (anti-tumor necrosis factor-a, anti-interleukin 12/23, anti-interleukin 17A, or apremilast regimen) with the effects of cyclosporine on vascular function as assessed by pulse wave velocity, augmentation index and central aortic blood pressure,

  3. Comparison of effect (improvement or deterioration) of treatment with biological vs. non biological agents on cardiac function in psoriasis [ Time Frame: 12 weeks ]
    Comparison of effect (improvement or deterioration) of treatment with biological agents (anti-tumor necrosis factor-a, anti-interleukin 12/23 ,anti-interleukin 17A, or apremilast regimen) with the effects of cyclosporine on cardiac function as assessed by longitudinal myocardial deformation, twisting and untwisting of the left ventricle


Secondary Outcome Measures :
  1. Differences and similarities in endothelial function between psoriasis and control groups [ Time Frame: 0 and 12 weeks ]
    Differences in endothelial function between psoriasis and normal controls, and similarities in endothelial function between psoriasis and coronary artery disease patients and untreated hypertension patients before and after 4 week of anti-inflammatory treatment in patients with psoriasis .The following parameters will be compared among the study subgroups endothelial function as assessed by flow mediated dilatation of the brachial artery, coronary flow reserve and endothelial glycocalyx thickness

  2. Differences and similarities in vascular function between psoriasis and control groups [ Time Frame: 0 and 12 weeks ]
    Differences in vascular function between psoriasis and normal controls, and similarities in vascular function between psoriasis and coronary artery disease patients and untreated hypertension patients before and after 4 week of anti-inflammatory treatment in patients with psoriasis .The following parameters will be compared among the study subgroups vascular function as assessed by pulse wave velocity, augmentation index and central aortic blood pressure,

  3. Differences and similarities in cardiac function between psoriasis and control groups [ Time Frame: 0 and 12 weeks ]
    Differences in cardiac function between psoriasis and normal controls, and similarities in cardiac function between psoriasis and coronary artery disease patients and untreated hypertension patients before and after 4 week of anti-inflammatory treatment in patients with psoriasis The following parameters will be compared among the study subgroups cardiac function as assessed by longitudinal myocardial deformation, twisting and untwisting of the left ventricle



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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • patients with psoriasis
  • Age and sex matched patients with CAD, with untreated hypertension and healthy subjects

Exclusion Criteria:

  • for psoriasis patients were presence of wall motion abnormalities and ejection fraction ≤ 50%, psoriatic arthritis, history of acute coronary syndrome, familial hyperlipidemia, insulin dependent-diabetes mellitus, chronic obstructive pulmonary disease or asthma, moderate or severe valvular heart disease, primary cardiomyopathies and malignant tumors. CAD was excluded in psoriasis patients by absence of clinical history, angina and reversible myocardial ischemia, as assessed by dobutamine stress echocardiography or thallium scintigraphy
  • regarding the group of CAD patients, we only included patients without history of ST elevation myocardial infarction in order to exclude the presence of transmural scar compromising myocardial function indices. Thus, CAD patients with wall motion abnormalities and ejection fraction of ≤ 50% were excluded. In addition, exclusion criteria, were history of acute coronary syndrome without ST-segment elevation within the last year, familial hyperlipidemia, insulin dependent-diabetes mellitus, chronic obstructive pulmonary disease or asthma, moderate or severe valvular heart disease, primary cardiomyopathies and malignant tumor
  • in normal controls, CAD was excluded by the presence of normal ECG, absence of clinical history and absence of reversible ischemia by means of treadmill test or dobutamine stress echocardiography

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02144857


Contacts
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Contact: Ignatios Ikonomidis, Dr 2105831264 ignoik@gmail.com
Contact: Maria Varoudi, Dr 6909001116 mvaroudi@gmail.com

Locations
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Greece
Attikon Hospital Recruiting
Athens, Greece, 12462
Contact: Ignatios Ikonomidis, Dr    +302105832187    ignoik@gmail.com   
Principal Investigator: Ignatios Ikonomidis, Dr         
Sponsors and Collaborators
University of Athens
Investigators
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Principal Investigator: Ignatios Ikonomidis, Dr University of Athens

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Ignatios Ikonomidis, Assistant Professor in Cardiology, University of Athens
ClinicalTrials.gov Identifier: NCT02144857     History of Changes
Other Study ID Numbers: 213/19-6-12
First Posted: May 22, 2014    Key Record Dates
Last Update Posted: December 28, 2018
Last Verified: December 2018

Additional relevant MeSH terms:
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Psoriasis
Skin Diseases, Papulosquamous
Skin Diseases
Cyclosporins
Cyclosporine
Etanercept
Ustekinumab
Apremilast
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Dermatologic Agents
Antirheumatic Agents
Calcineurin Inhibitors
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anti-Inflammatory Agents
Gastrointestinal Agents