Vascular Inflammation in Psoriasis Trial (The VIP Trial)

This study is currently recruiting participants.
Verified April 2013 by University of Pennsylvania
Sponsor:
Information provided by (Responsible Party):
University of Pennsylvania
ClinicalTrials.gov Identifier:
NCT01553058
First received: February 14, 2012
Last updated: May 8, 2013
Last verified: April 2013
  Purpose

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.


Condition Intervention Phase
Psoriasis
Cardiovascular Disease
Drug: Adalimumab (Humira)
Drug: Placebo Injection
Other: NB-UVB phototherapy
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Trial to Determine the Effect of Psoriasis Treatment on Cardiometabolic Disease

Resource links provided by NLM:


Further study details as provided by University of Pennsylvania:

Primary Outcome Measures:
  • Vascular Inflammation and Biomarkers [ Time Frame: Baseline, week 4 and week 12 ] [ Designated as safety issue: No ]
    • Change in total vascular inflammation of five aortic segments as assessed on FDG-PET/CT between baseline and week 12. Change in metabolic, lipid, and inflammatory biomarker levels between baseline, week 4 and 12


Secondary Outcome Measures:
  • Change in psoriasis activity (PASI-50, PASI-75, PASI-90, and PGA<1) [ Time Frame: baseline, week 4, 8 and 12 ] [ Designated as safety issue: No ]
    Psoriasis activity will be assessed using standard psoriasis measurements.

  • Number of patients with adverse events. [ Time Frame: Baseline, Week 4, 8 and 12 ] [ Designated as safety issue: Yes ]
    Safety will be assessed by comparing how many patients have adverse events depending on whether they are on adalimumab, as compared to NB-UVB phototherapy or placebo.

  • Change in patient-reported outcomes (e.g. EQ-5D, DLQI, MEDFICTS, and IPAQ) [ Time Frame: Baseline week 4, 8 and 12 ] [ Designated as safety issue: No ]
    Patient reported outcomes will be assessed using standard instruments.


Estimated Enrollment: 96
Study Start Date: July 2012
Estimated Study Completion Date: July 2017
Estimated Primary Completion Date: July 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Adalimumab (Humira)
Injection of the active drug Humira.
Drug: Adalimumab (Humira)
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 Comparator: Placebo Injection
Injection of placebo in place of active Humira injection.
Drug: Placebo Injection
Placebo injection will be given according to the same dose and schedule as the active comparator.
Active Comparator: NB-UVB phototherapy
NB-UVB Phototherapy 3 times per week, no other intervention.
Other: NB-UVB phototherapy
Phototherapy will be given 3 times per week according to the Fitzpatrick scale for skin types.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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:

    a. Women of childbearing potential must undergo monthly pregnancy testing during the study and agree to use two of the following methods of contraception throughout the 6-month study: i. Oral contraceptives; ii. Transdermal contraceptives iii. Injectable or implantable methods iv. Intrauterine devices v. Barrier methods (for example but not limited to a diaphragm with spermicide, condom with spermicide); or vi. Vasectomized partner Subjects using oral or parental forms of contraceptives must have been practicing birth control for at least three months prior to study drug administration.

    b. Women who are postmenopausal (for at least one year), sterile, or hysterectomized; c. Women who have undergone tubal ligation will be required to undergo monthly pregnancy testing during the duration of the study and agree to use a second form of contraception which includes: i. Oral contraceptives; ii. Transdermal contraceptives iii. Injectable or implantable methods iv. Intrauterine devices v. Barrier methods (for example but not limited to a diaphragm with spermicide, condom with spermicide); or vi. Vasectomized partner d. Sexual abstinence, defined as total abstinence from sexual intercourse, is considered an adequate form of contraception. (Agreement to comply with sexual abstinence must be recorded in the source document.)

  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
  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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01553058

Contacts
Contact: Suzette B VanderBeek, MPH 215-662-3514 suzette.baezvanderbeek@uphs.upenn.edu

Locations
United States, California
University of California, Davis Health System Recruiting
Sacramento, California, United States, 95816
Contact: Victoria Wells    916-734-1267    victoria.wells@ucdmc.ucdavis.edu   
Principal Investigator: April Armstrong, MD MPH         
United States, Connecticut
University of Connecticut Health Center Not yet recruiting
Farmington, Connecticut, United States, 06030
Contact: Gloria Borders, RN, MPH, CCRP    860-679-3475    borders@adp.uchc.edu   
Principal Investigator: Bruce Strober, MD         
United States, Maryland
National Heart, Lung, and Blood Institute Not yet recruiting
Bethesda, Maryland, United States, 20892
Contact: Amy Chi       chiah@nhlbi.nih.gov   
Principal Investigator: Nehal N Mehta, MD MSCE FAHA         
United States, New York
Buffalo Medical Group Recruiting
Buffalo, New York, United States, 14221
Contact: Judith Shand    716-630-1491    jshand@buffalomedicalgroup.com   
Principal Investigator: Robert E Kalb, MD         
United States, Pennsylvania
The University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19140
Principal Investigator: Joel Gelfand, MD MSCE         
United States, Utah
University of Utah Recruiting
Salt Lake City, Utah, United States, 84132
Contact: Sasha Hamel    801-213-2726    sasha.hamel@hsc.utah.edu   
Principal Investigator: Kristina Callis Duffin, MD         
Sponsors and Collaborators
University of Pennsylvania
Investigators
Principal Investigator: Joel Gelfand, MD MSCE University of Pennsylvania
  More Information

No publications provided

Responsible Party: University of Pennsylvania
ClinicalTrials.gov Identifier: NCT01553058     History of Changes
Other Study ID Numbers: 814278
Study First Received: February 14, 2012
Last Updated: May 8, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Pennsylvania:
Psoriasis
Cardiovascular Disease
FDG/PET-CT
NB-UVB Phototherapy
Vascular Inflammation
Lipid Biomarkers

Additional relevant MeSH terms:
Cardiovascular Diseases
Inflammation
Psoriasis
Pathologic Processes
Skin Diseases, Papulosquamous
Skin Diseases
Adalimumab
Antirheumatic Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on April 16, 2014