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Vascular Inflammation in Psoriasis - Extension Study (VIP-E)

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ClinicalTrials.gov Identifier: NCT01866592
Recruitment Status : Completed
First Posted : May 31, 2013
Results First Posted : May 22, 2018
Last Update Posted : May 22, 2018
Sponsor:
Collaborator:
AbbVie
Information provided by (Responsible Party):
University of Pennsylvania

Brief Summary:
VIP-E is a one-arm, open-label, 40-52 week extension study to continue or cross over subjects of the VIP study (# 814278) to active drug (adalimumab) to determine if there is sustained improvement in vascular inflammation, lipid metabolism, and inflammatory markers. VIP-E extends VIP study procedures for 40-52 weeks including questionnaires, physical exams, blood and urine samples, lab tests, one additional FDG-PET/CT scan, and adalimumab injections following FDA-approved psoriasis treatment regimen.

Condition or disease Intervention/treatment Phase
Psoriasis Cardiovascular Disease Drug: Adalimumab Phase 4

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 81 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Vascular Inflammation in Psoriasis - Extension Study
Study Start Date : April 2013
Actual Primary Completion Date : August 8, 2016
Actual Study Completion Date : October 27, 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Psoriasis
Drug Information available for: Adalimumab

Arm Intervention/treatment
Single-Arm, open-label extension trial
Single-arm, open label extension trial to continue treatment with Humira (Adalimumab) subcutaneous injection 80mg initial dose followed by 40mg maintenance dose every other week for up to 52 weeks.
Drug: Adalimumab
Study participants will receive the FDA-approved dosing schedule for Adalimumab (Humira): an initial dose of 80mg followed by a 40mg maintenance dose every other week up to 52 weeks.
Other Name: Humira




Primary Outcome Measures :
  1. Change in Vascular Inflammation [ Time Frame: 52 weeks (continuation group) or 64 weeks (crossover group) ]
    Change in total vascular inflammation of five aortic segments as assessed on FDG-PET/CT between week 52 of the adalimumab treatment period and baseline scans (prior to randomization in the VIP Trial). The arterial uptake of FDG is measured by the standardized uptake value (SUV) max divided by the venous SUIV mean yielding a target to background ration (TBR). If subjects were randomized to adalimumab in the VIP Trial, the time frame is a total of 52 weeks (continuation group). If subjects were randomized to placebo or phototherapy in the VIP Trial, additional 12 weeks added to the time frame for a total of 64 weeks (crossover group).

  2. Change in Vascular Inflammation [ Time Frame: 52 weeks of adalimumab treatment ]
    Change in total vascular inflammation of five aortic segments as assessed on FDG-PET/CT between week 52 of the adalimumab treatment period and start of adalimumab.The arterial uptake of FDG is measured by the standardized uptake value (SUV) max divided by the venous SUIV mean yielding a target to background ration (TBR).

  3. Change in Cardiometabolic Biomarker - Total Cholesterol [ Time Frame: 52 weeks (continuation group) or 64 weeks (crossover group) ]
    Change in metabolic, lipid, and inflammatory biomarker levels between week 52 of the adalimumab treatment period and baseline assessments from the VIP trial - Total Cholesterol. If subjects were randomized to adalimumab in the VIP Trial, the time frame is a total of 52 weeks (continuation group). If subjects were randomized to placebo or phototherapy in the VIP Trial, additional 12 weeks added to the time frame for a total of 64 weeks (crossover group).

  4. Change in Cardiometabolic Biomarker - Cholesterol Efflux [ Time Frame: 52 weeks (continuation group) or 64 weeks (crossover group) ]

    The ability to promote cholesterol efflux from macrophages is a classic function of HDL that is thought to be an important mechanism by which HDL protects against atherosclerosis. HDL cholesterol efflux capacity assays are performed based on published methods using J774 cells derived from a murine macrophage cell line (Mehta NN Atherosclerosis 2012). Efflux is calculated as a unitless measure by using the following formula: [(µCi of 3H-cholesterol in media containing apoB-depleted subject plasma - µCi of 3H-cholesterol in plasma-free media) / (µCi of 3H-cholesterol in media containing apoB-depleted pooled control plasma-µCi of 3H-cholesterol in pooled control plasma-free media)].

    If subjects were randomized to adalimumab in the VIP Trial, the time frame is a total of 52 weeks (continuation group). If subjects were randomized to placebo or phototherapy in the VIP Trial, additional 12 weeks added to the time frame for a total of 64 weeks (crossover group).


  5. Change in Cardiometabolic Biomarker - Low-density Lipoprotein Particle [ Time Frame: 52 weeks (continuation group) or 64 weeks (crossover group) ]
    Change in metabolic, lipid, and inflammatory biomarker levels between week 52 of the adalimumab treatment period and baseline assessments from the VIP trial - Low-density lipoprotein particle If subjects were randomized to adalimumab in the VIP Trial, the time frame is a total of 52 weeks (continuation group). If subjects were randomized to placebo or phototherapy in the VIP Trial, additional 12 weeks added to the time frame for a total of 64 weeks (crossover group).

  6. Change in Cardiometabolic Biomarker - High-density Lipoprotein Particle [ Time Frame: 52 weeks (continuation group) or 64 weeks (crossover group) ]
    Change in metabolic, lipid, and inflammatory biomarker levels between week 52 of the adalimumab treatment period and baseline assessments from the VIP trial - High-density lipoprotein particle If subjects were randomized to adalimumab in the VIP Trial, the time frame is a total of 52 weeks (continuation group). If subjects were randomized to placebo or phototherapy in the VIP Trial, additional 12 weeks added to the time frame for a total of 64 weeks (crossover group).

  7. Change in Cardiometabolic Biomarker - Log Insulin [ Time Frame: 52 weeks (continuation group) or 64 weeks (crossover group) ]
    Change in metabolic, lipid, and inflammatory biomarker levels between week 52 of the adalimumab treatment period and baseline assessments from the VIP trial - Log Insulin If subjects were randomized to adalimumab in the VIP Trial, the time frame is a total of 52 weeks (continuation group). If subjects were randomized to placebo or phototherapy in the VIP Trial, additional 12 weeks added to the time frame for a total of 64 weeks (crossover group).

  8. Change in Cardiometabolic Biomarker - Log Adiponectin [ Time Frame: 52 weeks (continuation group) or 64 weeks (crossover group) ]
    Change in metabolic, lipid, and inflammatory biomarker levels between week 52 of the adalimumab treatment period and baseline assessments from the VIP trial - Log Adiponectin If subjects were randomized to adalimumab in the VIP Trial, the time frame is a total of 52 weeks (continuation group). If subjects were randomized to placebo or phototherapy in the VIP Trial, additional 12 weeks added to the time frame for a total of 64 weeks (crossover group).

  9. Change in Cardiometabolic Biomarker - Log Leptin [ Time Frame: 52 weeks (continuation group) or 64 weeks (crossover group) ]
    Change in metabolic, lipid, and inflammatory biomarker levels between week 52 of the adalimumab treatment period and baseline assessments from the VIP trial - Log Leptin If subjects were randomized to adalimumab in the VIP Trial, the time frame is a total of 52 weeks (continuation group). If subjects were randomized to placebo or phototherapy in the VIP Trial, additional 12 weeks added to the time frame for a total of 64 weeks (crossover group).

  10. Change in Cardiometabolic Biomarker - Log C-reactive Protein [ Time Frame: 52 weeks (continuation group) or 64 weeks (crossover group) ]
    Change in metabolic, lipid, and inflammatory biomarker levels between week 52 of the adalimumab treatment period and baseline assessments from the VIP trial - Log C-reactive protein If subjects were randomized to adalimumab in the VIP Trial, the time frame is a total of 52 weeks (continuation group). If subjects were randomized to placebo or phototherapy in the VIP Trial, additional 12 weeks added to the time frame for a total of 64 weeks (crossover group).

  11. Change in Cardiometabolic Biomarker - Log Tumor Necrosis Factor-Alpha [ Time Frame: 52 weeks (continuation group) or 64 weeks (crossover group) ]
    Change in metabolic, lipid, and inflammatory biomarker levels between week 52 of the adalimumab treatment period and baseline assessments from the VIP trial - Log Tumor Necrosis Factor-Alpha If subjects were randomized to adalimumab in the VIP Trial, the time frame is a total of 52 weeks (continuation group). If subjects were randomized to placebo or phototherapy in the VIP Trial, additional 12 weeks added to the time frame for a total of 64 weeks (crossover group).

  12. Change in Cardiometabolic Biomarker - Log Interleukin 6 [ Time Frame: 52 weeks (continuation group) or 64 weeks (crossover group) ]
    Change in metabolic, lipid, and inflammatory biomarker levels between week 52 of the adalimumab treatment period and baseline assessments from the VIP trial - Log Interleukin 6 If subjects were randomized to adalimumab in the VIP Trial, the time frame is a total of 52 weeks (continuation group). If subjects were randomized to placebo or phototherapy in the VIP Trial, additional 12 weeks added to the time frame for a total of 64 weeks (crossover group).

  13. Change in Cardiometabolic Biomarker - GlycA [ Time Frame: 52 weeks (continuation group) or 64 weeks (crossover group) ]
    Change in metabolic, lipid, and inflammatory biomarker levels between week 52 of the adalimumab treatment period and baseline assessments from the VIP trial - GlycA If subjects were randomized to adalimumab in the VIP Trial, the time frame is a total of 52 weeks (continuation group). If subjects were randomized to placebo or phototherapy in the VIP Trial, additional 12 weeks added to the time frame for a total of 64 weeks (crossover group).

  14. Change in Cardiometabolic Biomarkers: - Total Cholesterol [ Time Frame: 52 weeks of adalimumab treatment ]
    Change in metabolic, lipid, and inflammatory biomarker levels between week 52 of the adalimumab treatment period and the start of adalimumab - Total Cholesterol

  15. Change in Cardiometabolic Biomarker - Cholesterol Efflux [ Time Frame: 52 weeks of adalimumab treatment ]
    Change in metabolic, lipid, and inflammatory biomarker levels between week 52 of the adalimumab treatment period and baseline assessments from the VIP trial - Cholesterol Efflux

  16. Change in Cardiometabolic Biomarker - Low-density Lipoprotein Particle [ Time Frame: 52 weeks of adalimumab treatment ]
    Change in metabolic, lipid, and inflammatory biomarker levels between week 52 of the adalimumab treatment period and baseline assessments from the VIP trial - Low-density lipoprotein particle

  17. Change in Cardiometabolic Biomarker - High-density Lipoprotein Particle [ Time Frame: 52 weeks of adalimumab treatment ]
    Change in metabolic, lipid, and inflammatory biomarker levels between week 52 of the adalimumab treatment period and baseline assessments from the VIP trial - High-density lipoprotein particle

  18. Change in Cardiometabolic Biomarker - Log Insulin [ Time Frame: 52 weeks of adalimumab treatment ]
    Change in metabolic, lipid, and inflammatory biomarker levels between week 52 of the adalimumab treatment period and baseline assessments from the VIP trial - Log Insulin

  19. Change in Cardiometabolic Biomarker - Log Adiponectin [ Time Frame: 52 weeks of adalimumab treatment ]
    Change in metabolic, lipid, and inflammatory biomarker levels between week 52 of the adalimumab treatment period and baseline assessments from the VIP trial - Log Adiponectin

  20. Change in Cardiometabolic Biomarker - Log Leptin [ Time Frame: 52 weeks of adalimumab treatment ]
    Change in metabolic, lipid, and inflammatory biomarker levels between week 52 of the adalimumab treatment period and baseline assessments from the VIP trial - Log Leptin

  21. Change in Cardiometabolic Biomarker - Log C-reactive Protein [ Time Frame: 52 weeks of adalimumab treatment ]
    Change in metabolic, lipid, and inflammatory biomarker levels between week 52 of the adalimumab treatment period and baseline assessments from the VIP trial - Log C-reactive protein

  22. Change in Cardiometabolic Biomarker - Log Tumor Necrosis Factor-Alpha [ Time Frame: 52 weeks of adalimumab treatment ]
    Change in metabolic, lipid, and inflammatory biomarker levels between week 52 of the adalimumab treatment period and baseline assessments from the VIP trial - Log Tumor Necrosis Factor-Alpha

  23. Change in Cardiometabolic Biomarker - Log Interleukin 6 [ Time Frame: 52 weeks of adalimumab treatment ]
    Change in metabolic, lipid, and inflammatory biomarker levels between week 52 of the adalimumab treatment period and baseline assessments from the VIP trial - Log Interleukin 6

  24. Change in Cardiometabolic Biomarker - GlycA [ Time Frame: 52 weeks of adalimumab treatment ]
    Change in metabolic, lipid, and inflammatory biomarker levels between week 52 of the adalimumab treatment period and baseline assessments from the VIP trial - GlycA


Secondary Outcome Measures :
  1. Psoriasis Activity (PASI and PGA) [ Time Frame: 52 weeks (continuation group) or 64 weeks (crossover group) ]

    Change in psoriasis activity will be assessed using the following standardized measurement tools for psoriasis: Psoriasis Area and Severity Index (PASI) and Physician's Global Assessment (PGA). PASI combines the assessment of the severity of lesions and the area affected into a single score with range 0 (no disease) to 72 maximal disease. The PGA is an average assessment of all psoriatic lesions based on erythema, scale, and induration with score range 0 (no disease/clear) to 5 (maximal disease).

    If subjects were randomized to adalimumab in the VIP Trial, the time frame is a total of 52 weeks (continuation group). If subjects were randomized to placebo or phototherapy in the VIP Trial, additional 12 weeks added to the time frame for a total of 64 weeks (crossover group).


  2. Safety/Adverse Events [ Time Frame: Baseline - Week 52 ]
    Safety will be assessed by evaluating all subject reported adverse events through the duration of the study.

  3. Change in Patient-Reported Quality of Life Outcomes-EuroQol EQ-5D [ Time Frame: 52 weeks (continuation group) or 64 weeks (crossover group) ]
    EQ-5D is a standardized instrument developed by the EuroQol Group as a measure of health-related quality of life that can be used in a wide range of health conditions and treatments. The EQ-5D consists of a descriptive system and the EQ VAS. The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression on a scale ranging from 1 (no health state problem) to 3 (extreme health state problems). The EQ VAS records the patient's self-rated health on a vertical visual analogue scale ranging from 0, worst health state, to 100, best health state. A scoring function is used to assign a value (i.e., EQ-5D™ index score) to self-reported health states from a set of population-based preference weights. For the U.S. general population, the possible EQ-5D index scores range from -0.11 to 1.0 where 0.0 = death and 1.0 = perfect health.

  4. Change in Patient-Reported Quality of Life Outcomes - Dermatology Life Quality Index (DLQI) [ Time Frame: 52 weeks (continuation group) or 64 weeks (crossover group) ]

    The DLQI is calculated by summing the score of 10 questions regarding impact of skin condition on daily life resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired.

    If subjects were randomized to adalimumab in the VIP Trial, the time frame is a total of 52 weeks (continuation group). If subjects were randomized to placebo or phototherapy in the VIP Trial, additional 12 weeks added to the time frame for a total of 64 weeks (crossover group).


  5. Change in Patient-Reported Quality of Life Outcomes - MEDFICTS Dietary Assessment [ Time Frame: 52 weeks (continuation group) or 64 weeks (crossover group) ]

    Patient reported dietary outcomes will be assessed using MEDFICTS (Meats, Eggs, Dairy, Fried foods, fat In baked goods, Convenience foods, fats added at the Table, and Snacks), a brief dietary assessment instrument. This assessment looks at eight different categories of foods and assigns points by type of food and serving size ranging from 0 points (do not consume that food group) to 21 points (consume food group, largest serving size). Your final score is the total of all points for all food categories.

    If subjects were randomized to adalimumab in the VIP Trial, the time frame is a total of 52 weeks (continuation group). If subjects were randomized to placebo or phototherapy in the VIP Trial, additional 12 weeks added to the time frame for a total of 64 weeks (crossover group).


  6. Change in Patient-Reported Quality of Life Outcomes - International Physical Activity Questionnaire (IPAQ) [ Time Frame: 52 weeks (continuation group) or 64 weeks (crossover group) ]

    IPAQ is an instrument designed primarily for population surveillance of physical activity among adults with activity measured in metabolic equivalent (MET)-minutes per week.

    Per Office of Disease Prevention and Health Promotion's Physical Activity Guidelines:

    A range of 500 to 1,000 MET-minutes of activity per week provides substantial [health] benefit, and amounts of activity above this range have even more benefit. Amounts of activity below this range also have some benefit. The dose-response relationship continues even within the range of 500 to 1,000 MET-minutes, in that the health benefits of 1,000 MET-minutes per week are greater than those of 500 MET-minutes per week.

    If subjects were randomized to adalimumab in the VIP Trial, the time frame is a total of 52 weeks (continuation group). If subjects were randomized to placebo or phototherapy in the VIP Trial, additional 12 weeks added to the time frame for a total of 64 weeks (crossover group).




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Males and females 18 years of age and older.
  2. Subject completed the VIP Study
  3. Subject willing and able to avoid prolonged exposure of skin affected by psoriasis to natural or sunlight or tanning beds during the course of the study
  4. Subject is willing and able to avoid topical or systemic prescription treatments for psoriasis besides adalimumab during the course of the study
  5. Women are eligible to participate in the study if they meet one of the following criteria:

    1. Women of childbearing potential must undergo pregnancy testing during the baseline visit and agree to use one of the following methods of contraception throughout the 13-month study:

      • Oral contraceptives;
      • Transdermal contraceptives
      • Injectable or implantable methods
      • Intrauterine devices
      • Barrier methods (for example but not limited to a diaphragm with spermicide, condom with spermicide); or
      • Vasectomized partner
      • Subjects using oral or parental forms of contraceptives must have been using those methods of birth control for at least three months prior to the baseline visit.
    2. Women who have undergone tubal ligation
    3. Women who are postmenopausal (for at least one year), sterile, or hysterectomized 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.
  6. Subject is judged to be in good general health as determined by the Principal Investigator based upon the results of medical history, laboratory profile, and physical examination.
  7. 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 that led to discontinuation of the TNF inhibitor and contraindicates future treatment.
  2. Previous lack of response to a TNF-alpha antagonist led to discontinuation.
  3. Diagnosis of erythrodermic psoriasis, generalized pustular psoriasis, or medication-induced or medication-exacerbated psoriasis.
  4. Diagnosis of other active skin diseases or skin infections (bacterial, fungal, or viral) that may interfere with evaluation of psoriasis.
  5. Subject is taking or requires oral or injectable corticosteroids during the study. Inhaled corticosteroids for stable medical conditions are allowed.
  6. 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.
  7. History of diabetes mellitus, type 1 or type 2 (patients with type 2 diabetes may be enrolled if the duration of diabetes is <10 years and HbA1c is <7.0%)
  8. Uncontrolled hypertension, with measured systolic blood pressure >180 mmHg or diastolic blood pressure >90 mmHg
  9. History of demyelinating diseases or lupus.
  10. Subject has infection or risk factors for severe infections, for example:

    • 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 as determined within 6 months of the baseline visit for VIP-E; 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 will require a live vaccination during study participation including up to 30 days after the last dose of study drug.
  11. Subject has history of hematological or solid malignancy within the past five years other than successfully treated basal cell carcinoma, non-metastatic cutaneous squamous cell carcinoma or cervical carcinoma in situ.
  12. Female subject who is pregnant or breast-feeding or considering becoming pregnant during the study.
  13. Clinic 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

      • 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)
  14. Recent history of substance abuse or psychiatric illness that could preclude compliance with the protocol.
  15. If subject is on cholesterol-lowering medication (e.g. statin), dose and form of medication must be stable for 90 days prior to baseline and remain stable throughout the duration of the study.

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): NCT01866592


Locations
United States, California
University of California, Davis Health System
Sacramento, California, United States, 95816
United States, Colorado
University of Colorado
Denver, Colorado, United States, 80045
United States, Maryland
National Heart, Lung, and Blood Institute
Bethesda, Maryland, United States, 20892
United States, New York
Buffalo Medical Group
Buffalo, New York, United States, 14221
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
Menter Dermatology Research Institute
Dallas, Texas, United States, 75246
Center for Clinical Studies
Houston, Texas, United States, 77004
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84132
Sponsors and Collaborators
University of Pennsylvania
AbbVie
Investigators
Principal Investigator: Joel M Gelfand, MD MSCE University of Pennsylvania

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of Pennsylvania
ClinicalTrials.gov Identifier: NCT01866592     History of Changes
Other Study ID Numbers: 817552
First Posted: May 31, 2013    Key Record Dates
Results First Posted: May 22, 2018
Last Update Posted: May 22, 2018
Last Verified: April 2018

Keywords provided by University of Pennsylvania:
Psoriasis
Cardiovascular Disease
Vascular Inflammation
Lipid Biomarkers
Metabolic biomarkers
FDG-PET/CT

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