Vascular Inflammation in Psoriasis Trial (The VIP Trial)
Condition: Psoriasis; Cardiovascular Disease
MeSH terms: Cardiovascular Diseases; Psoriasis
Intervention: Adalimumab (Humira); Placebo Injection; NB-UVB phototherapy
Intervention description: Humira will be given at an initial dose of 80mg followed by 40 mg the second week, subsequent doses will be given at 40mg and follow FDA dosing schedule.; Placebo injection will be given according to the same dose and schedule as the active comparator.; Phototherapy will be given 3 times per week according to the Fitzpatrick scale for skin types.
Intervention MeSH terms: Adalimumab
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 97.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Psoriasis; Cardiovascular Disease; FDG/PET-CT; NB-UVB Phototherapy; Vascular Inflammation; Lipid Biomarkers

Summary:

      The purpose of this study is to assess the effect of adalimumab (Humira), when compared to
      NB-UVB (narrow-band ultraviolet B) phototherapy or placebo (an inactive substance that may
      resemble an active substance but has no medical value) injection. The study will compare the
      effects of each on systemic inflammation and cardiovascular disease risk factors in subjects
      diagnosed with moderate to severe psoriasis.

      This study will look for systemic vascular inflammation in subjects with a test called
      FDG-PET/CT (Fluorodeoxyglucose-positron emission tomography/computed tomography). The study
      will also look for cardio metabolic (heart disease and metabolic factors such as diabetes)
      identifiers in the blood. A blood sample will be taken that will look for these markers
      identifying high cholesterol, cholesterol efflux function (the ability of cholesterol to move
      in the body), metabolic factors, and inflammation.

      This study will also assess the effect of adalimumab (Humira), when compared to NB-UVB
      phototherapy or placebo injection on psoriasis activity and severity. The study will also
      compare the safety of adalimumab (Humira) to NB-UVB phototherapy or placebo injection. This
      study will also evaluate subjects' reported outcomes through a questionnaire that will assess
      quality-of-life in subjects living with psoriasis.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Males and females 18 years of age and older.

          2. Clinical diagnosis of psoriasis for at least 6 months as determined by subject
             interview of his/her medical history and confirmation of diagnosis through physical
             examination by Investigator.

          3. Stable plaque psoriasis for at least 2 months before Screening and at Baseline (Week
             0) as determined by subject interview of his/her medical history.

          4. Moderate to severe psoriasis defined by ≥ 10 percent Body Surface Area (BSA)
             involvement at the Baseline (Week 0) visit.

          5. PASI (psoriasis assessment and severity index) score of ≥ 12 at the Baseline (Week 0)
             visit.

          6. Subject is a candidate for systemic therapy or phototherapy and has active psoriasis
             despite prior treatment with topical agents.

          7. Women are eligible to participate in the study if they meet one of the following
             criteria:

               1. Women of childbearing potential who are willing to undergo regular pregnancy
                  testing and agree to use one method of contraception throughout the study are
                  eligible to participate

               2. Women who are postmenopausal (for at least one year), sterile, or hysterectomized
                  are eligible to participate

               3. Women who have undergone tubal ligation are eligible to participate

               4. Women who agree to be sexually abstinent, defined as total abstinence from sexual
                  intercourse, as a form of contraception are eligible to participate in the study.

          8. Subject 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 12-lead electrocardiogram (ECG) performed at screening.

          9. Able and willing to give written informed consent and to comply with requirements of
             this study protocol.

        Exclusion Criteria:

          1. Previous adverse event following exposure to a TNF-alpha antagonist and/or UV
             phototherapy that led to discontinuation of either of these therapies and
             contraindicates future treatment.

          2. Previous lack of response to a TNF-alpha antagonist and/or UV phototherapy that led to
             discontinuation of either of these therapies.

          3. Diagnosis of erythrodermic psoriasis, generalized or localized pustular psoriasis,
             medication-induced or medication-exacerbated psoriasis, or new onset guttate
             psoriasis.

          4. Diagnosis of other active skin diseases or skin infections (bacterial, fungal, or
             viral) that may interfere with evaluation of psoriasis.

          5. Cannot avoid UVB phototherapy for at least 14 days prior to the Baseline (Week 0)
             visit.

          6. Cannot avoid psoralen-UVA phototherapy for at least 30 days prior to the Baseline
             (Week 0) visit and during the study.

          7. Cannot discontinue systemic therapies for the treatment of psoriasis, or systemic
             therapies known to improve psoriasis, during the study:

               -  Systemic (investigational or marketed) therapies must be discontinued at least 30
                  days prior to the Baseline (Week 0) visit except for biologics.

                    -  All biologics, except ustekinumab, must be discontinued for at least 90 days
                       prior to Baseline (Week 0).

                    -  The IL-12/IL-23 antagonist ustekinumab (half-life of 45.6 ± 80.2 days) must
                       be discontinued for at least 180 days prior to Baseline (Week 0).

               -  Investigational agents must be discontinued at least 30 days or 5 half-lives
                  (whichever is longer) prior to the Baseline (Week 0) visit.

          8. Subject is taking or requires oral or injectable corticosteroids during the study.
             Inhaled corticosteroids for stable medical conditions are allowed.

          9. Poorly controlled medical condition, such as unstable ischemic heart disease,
             congestive heart failure, recent cerebrovascular accidents, psychiatric disease
             requiring frequent hospitalization, and any other condition, which, in the opinion of
             the Investigator, would put the subject at risk by participation in the study.

         10. History of diabetes mellitus, type 1 or type 2 - note that patients with type 2
             diabetes may be enrolled if the duration of diabetes is <10 years and HbA1c is <7.0%)

         11. Uncontrolled hypertension, with measured systolic blood pressure >180 mmHg or
             diastolic blood pressure >90 mmHg

         12. History of demyelinating diseases or lupus.

         13. Subject has infection or risk factors for severe infections, for example:

               -  Positive serology or known history of HIV, hepatitis B or C, or other severe,
                  recurrent, or persistent infections;

               -  Excessive immunosuppression or other factors associated with it, including human
                  immunodeficiency virus infection;

               -  Active tuberculosis (TB) disease;

               -  Evidence of latent TB infection demonstrated by Purified Protein Derivative (PPD)
                  ≥ 5 mm of induration or positive Quantiferon-GOLD results; except if prophylactic
                  treatment for TB, as recommended by local guidelines, is initiated prior to
                  administration of study drug or if there is documentation that the subject has
                  received prophylactic treatment for TB previously.

               -  Any other significant infection requiring hospitalization or intravenous (IV)
                  antibiotics in the month prior to Baseline;

               -  Infection requiring treatment with oral or parenteral antibiotics within 14 days
                  prior to Baseline;

               -  Subject has received vaccination with Bacille Calmette-Guerin (BCG) within 365
                  days prior to Screening;

               -  Subject has received vaccination with a live viral agent 30 days prior to
                  Screening or will require a live vaccination during study participation including
                  up to 30 days after the last dose of study drug.

         14. Subject has history of hematological or solid malignancy other than successfully
             treated basal cell carcinoma, non-metastatic cutaneous squamous cell carcinoma or
             cervical carcinoma in situ.

         15. Female subject who is pregnant or breast-feeding or considering becoming pregnant
             during the study.

         16. Screening clinical laboratory analyses showing any of the following abnormal results:

               -  Hemoglobin (Hgb) < 10 g/dL in females or <12 g/dL in males;

               -  White blood cell (WBC) count <2.5 x 109/L

                  o Subject can be included if WBC count is <2.5 x x 109/L and absolute neutrophil
                  count (ANC) is >1000 cells / mm3.

               -  WBC count > 15 x 109/L;

               -  Platelet count < 100 x 109/L;

               -  Serum aspartate transaminase (AST) or alanine transaminase (ALT) >2.5 upper
                  limits of normal (ULN);

               -  Serum total bilirubin ≥2 mg/dL (≥26 µmol/L); or

               -  Serum creatinine >1.6 mg/dL (>141 µmol/L).

         17. Recent history of substance abuse or psychiatric illness that could preclude
             compliance with the protocol.

         18. History of any substance abuse within 365 days of screening visit

         19. Alcohol use >14 drinks per week at the screening visit or within 30 days of the
             screening period

         20. If subject is on cholesterol-lowering medication (e.g. statin), dose and form of
             medication must be stable for 90 days prior to week 0 and remain stable throughout the
             duration of the study.

         21. History of photosensitivity of medical condition that may be exacerbated by UV
             exposures such as lupus or dermatomyositis