Comparative Effectiveness of Psoriasis Treatments on Systemic Inflammation

NCT02330380 | Completed

• 1 other identifier: 04-13-21
• Study Type: observational
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective longitudinal observational pilot study of psoriasis patients on continuous standard-of-care systemic therapeutics to determine the level of change in established (plasma/serum) and investigative (cellular) biomarkers that are associated with increased risk of CVD events. The final endpoint of the proposed study will be a ranking of the examined biomarkers based upon an integrated assessment of biomarker behavior over time. Secondary outcomes will assess changes in coronary artery calcification scoring, PET-MRI, skin biopsies, and clinical improvement.

Conditions

Psoriasis; Inflammation

Keywords

psoriasis, comparative effects, inflammation

Outcome Measures

Primary Outcomes (1)

• Biomarker assessment

  The biomarkers examined throughout the study will be assessed. And, an integrated assessment of biomarker behavior over time will be performed. Biomarkers examined will include High sensitivity C-reactive protein (hsCRP), Myeloperoxidase (MPO), resistin, adiponectin and leptin.

  52 weeks

Secondary Outcomes (4)

• Changes in coronary artery calcification scoring

  52 weeks

• Changes in PET-MRI

  52 weeks

• Clinical improvement

  52 weeks

• Changes in skin biopsies

  52 weeks

Study Arms (7)

Methotrexate

Methotrexate will be dosed weekly. Methotrexate is given as a single, weekly dose and is will be started at 15mg after a first week test dose of 2.5 mg to minimize side effects and achieve efficacy. Weekly dosages will be 15mg.

Drug: Methotrexate

Ustekinumab

Ustekinumab is given as a subcutaneous injection of 45mg if the patient is \<100Kg or 90mg if the patient is \>100Kg at weeks 0, 4, 16, and every 12 weeks thereafter.

Drug: Ustekinumab

Etanercept

Etanercept will be given in the first 3 months of treatment as 50 mg twice a week (3 or 4 days apart). After 3 months, a reduced dose of 50 mg will be given once per week.

Drug: Etanercept

Adalimumab

Adalimumab will be given in a dose of 40 mg subcutaneously every other week.

Drug: Adalimumab

Acitretin

Acetretin will be prescribed as daily with 25mg if the patient is \<80Kg or 35mg if the patient is \>80Kg.

Drug: Acitretin

UVB Excimer Laser

Dose determination will be determined by a physician per standard-of-care by performing a Sunburn Test/Minimal Erythemal Dose Test, or by visually evaluating the patient's skin type and thickness of psoriasis plaque. Initial laser dose will be 1-4X the MED depending on the thickness of the plaque. Escalation will be 25-50% increase in dose per treatment if there is no residual erythema, 25% increase per treatment if there is mild residual erythema, and 0% increase per treatment if there is moderate residual erythema. Investigators also have the option to skip a treatment, if there is above moderate erythema, or significant patient discomfort. Patients will receive treatment twice a week.

Other: UVB Excimer Laser

Narrowband UVB

Narrowband UVB (311nm) will be used to treat patients 3X per week with 311nm of UVB light. Uninvolved areas of skin will be covered where possible to minimize excess sun exposure. Patients will be tested for their minimal erythemal dose (MED), after which, based upon Fitzpatrick Scale skin type, a patient will typically beginning with 1-2 minutes based on skin type and gradually increased by 10-15% per treatment dose as tolerated.

Other: Narrowband UVB

Interventions

Methotrexate DRUG

Subjects will receive Methotrexate as detailed in the "Group" description.

Methotrexate

Ustekinumab DRUG

Subjects will receive Ustekinumab as detailed in the "Group" description.

Ustekinumab

Etanercept DRUG

Subjects will receive Etanercept as detailed in the "Group" description.

Etanercept

Adalimumab DRUG

Subjects will receive Adalimumab as detailed in the "Group" description.

Adalimumab

Acitretin DRUG

Subjects will receive Acitretin as detailed in the "Group" description.

Acitretin

UVB Excimer Laser OTHER

Subjects will receive UVB Excimer Laser therapy as detailed in the "Group" description.

UVB Excimer Laser

Narrowband UVB OTHER

Subjects will receive Narrowband UVB as detailed in the "Group" description.

Narrowband UVB

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Psoriasis patients

You may qualify if:

• Subjects ages 18-65 years old
• Diagnosis of moderate-to-severe plaque psoriasis
• Plaque affects ≥ 10% of subject's body surface area (BSA)
• Subjects prescribed one of the following standard-of-care treatments for their psoriasis: Ustekinumab, Methotrexate, Etanercept, Adalimumab, Narrow Band UVB (311nm), Excimer Laser Treatment (308nm), or Acitretin
• Subjects willing to complete a Washout Period prior to Visit 1 (only for subjects currently on a psoriasis treatment):
• Discontinue systemic therapies for at least 4 weeks
• Discontinue topical therapies for at least 2 weeks
• Discontinue phototherapies for at least 2 weeks

You may not qualify if:

• Subjects who are currently on a psoriasis treatment and unwilling to go through the washout-period
• Subjects with a critical illness or who are immunocompromised
• Weight is 400lbs or greater
• Subjects who are currently pregnant or breastfeeding
• Subjects who have metal implants
• Subjects who have a pacemaker, stent, or artificial heart valve
• History of clinically significant hematological, renal or liver disease
• Patients with known co-morbidities that raise biomarkers such as:
• History of myocardial infarction (MI)
• History of cerebrovascular accident (CVA)
• Significant atherosclerosis (defined as the presence of any carotid plaque; or carotid intimal media thickness (cIMT) \>75th percentile for age; or the presence of coronary artery calcium score\>100)
• Poorly controlled diabetes (elevated HbA1c \> 8.5)

Sponsors & Collaborators

• University Hospitals Cleveland Medical Center: lead
• National Psoriasis Foundation: collaborator

Study Sites (1)

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Related Publications (9)

• Alora-Palli MB, Brouda I, Green B, Kimball AB. A cost-effectiveness comparison of liquor carbonis distillate solution and calcipotriol cream in the treatment of moderate chronic plaque psoriasis. Arch Dermatol. 2010 Aug;146(8):919-22. doi: 10.1001/archdermatol.2010.167. No abstract available.

  PMID: 20713833 BACKGROUND

• Ho SG, Yeung CK, Chan HH. Methotrexate versus traditional Chinese medicine in psoriasis: a randomized, placebo-controlled trial to determine efficacy, safety and quality of life. Clin Exp Dermatol. 2010 Oct;35(7):717-22. doi: 10.1111/j.1365-2230.2009.03693.x.

  PMID: 19925489 BACKGROUND

• Flytstrom I, Stenberg B, Svensson A, Bergbrant IM. Methotrexate vs. ciclosporin in psoriasis: effectiveness, quality of life and safety. A randomized controlled trial. Br J Dermatol. 2008 Jan;158(1):116-21. doi: 10.1111/j.1365-2133.2007.08284.x. Epub 2007 Nov 6.

  PMID: 17986302 BACKGROUND

• Heydendael VM, Spuls PI, Opmeer BC, de Borgie CA, Reitsma JB, Goldschmidt WF, Bossuyt PM, Bos JD, de Rie MA. Methotrexate versus cyclosporine in moderate-to-severe chronic plaque psoriasis. N Engl J Med. 2003 Aug 14;349(7):658-65. doi: 10.1056/NEJMoa021359.

  PMID: 12917302 BACKGROUND

• Reich K, Sinclair R, Roberts G, Griffiths CE, Tabberer M, Barker J. Comparative effects of biological therapies on the severity of skin symptoms and health-related quality of life in patients with plaque-type psoriasis: a meta-analysis. Curr Med Res Opin. 2008 May;24(5):1237-54. doi: 10.1185/030079908x291985. Epub 2008 Mar 19.

  PMID: 18355421 BACKGROUND

• Atteno M, Peluso R, Costa L, Padula S, Iervolino S, Caso F, Sanduzzi A, Lubrano E, Del Puente A, Scarpa R. Comparison of effectiveness and safety of infliximab, etanercept, and adalimumab in psoriatic arthritis patients who experienced an inadequate response to previous disease-modifying antirheumatic drugs. Clin Rheumatol. 2010 Apr;29(4):399-403. doi: 10.1007/s10067-009-1340-7.

  PMID: 20066450 BACKGROUND

• Saurat JH, Stingl G, Dubertret L, Papp K, Langley RG, Ortonne JP, Unnebrink K, Kaul M, Camez A; CHAMPION Study Investigators. Efficacy and safety results from the randomized controlled comparative study of adalimumab vs. methotrexate vs. placebo in patients with psoriasis (CHAMPION). Br J Dermatol. 2008 Mar;158(3):558-66. doi: 10.1111/j.1365-2133.2007.08315.x. Epub 2007 Nov 28.

  PMID: 18047523 BACKGROUND

• Mehta NN, Yu Y, Saboury B, Foroughi N, Krishnamoorthy P, Raper A, Baer A, Antigua J, Van Voorhees AS, Torigian DA, Alavi A, Gelfand JM. Systemic and vascular inflammation in patients with moderate to severe psoriasis as measured by [18F]-fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET/CT): a pilot study. Arch Dermatol. 2011 Sep;147(9):1031-9. doi: 10.1001/archdermatol.2011.119. Epub 2011 May 16.

  PMID: 21576552 BACKGROUND

• Gelfand JM, Wan J, Callis Duffin K, Krueger GG, Kalb RE, Weisman JD, Sperber BR, Stierstorfer MB, Brod BA, Schleicher SM, Bebo BF Jr, Troxel AB, Shin DB, Steinemann JM, Goldfarb J, Yeung H, Van Voorhees AS. Comparative effectiveness of commonly used systemic treatments or phototherapy for moderate to severe plaque psoriasis in the clinical practice setting. Arch Dermatol. 2012 Apr;148(4):487-94. doi: 10.1001/archdermatol.2012.370.

  PMID: 22508874 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Skin biopsies and blood samples will be collected

MeSH Terms

Conditions

Psoriasis; Inflammation

Interventions

Methotrexate; Ustekinumab; Etanercept; Adalimumab; Acitretin

Condition Hierarchy (Ancestors)

Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immunoglobulin Fc Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Immunoglobulin Constant Regions; Receptors, Tumor Necrosis Factor; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Terpenes; Pigments, Biological; Biological Factors

Study Officials

• Neil Korman, MD

  University Hospitals Cleveland Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 30, 2014
• First Posted: January 1, 2015
• Study Start: April 1, 2013
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: October 13, 2017

Record last verified: 2017-10

Locations

US (1)