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Vascular Inflammation in Psoriasis-Ustekinumab (VIP-U) (VIP-U)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02187172
Recruitment Status : Completed
First Posted : July 10, 2014
Results First Posted : August 15, 2019
Last Update Posted : August 15, 2019
Sponsor:
Collaborator:
Janssen Scientific Affairs, LLC
Information provided by (Responsible Party):
University of Pennsylvania

Brief Summary:

The VIP-U Study is a clinical trial designed to investigate the effect of ustekinumab (Stelara) and placebo on reducing vascular inflammation and cardiometabolic risk biomarkers in patients with moderate to severe psoriasis.

This study will look for systemic vascular inflammation in study participants with a test called FDG PET/CT (fluorodeoxyglucose-positron emission tomography/computed tomography). The study will also look for cardiometabolic identifiers (heart disease and metabolic factors) in blood samples, including markers of high cholesterol, cholesterol efflux function (the ability of cholesterol to move in the body), metabolic factors, and inflammation.

The study will also examine the effects of ustekinumab compared to placebo on psoriasis activity, severity and safety.


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

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 43 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: A hybrid RCT (randomized controlled trial) crossover trial where all patients receive total of 52 weeks of active treatment following an RCT phase of 12 weeks (active treatment or placebo). Patients randomized to active treatment will receive additional 40 weeks of active treatment at end of RCT phase; patients randomized to placebo will receive 52 weeks of active treatment at end of RCT phase. Primary outcomes are assessed at end of the RCT phase (comparison of interventions in change from start of treatment) and at end of 52 weeks of active treatment (change from start of treatment).
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A PHASE IV, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF THE EFFECTS OF USTEKINUMAB ON VASCULAR INFLAMMATION IN PSORIASIS
Study Start Date : July 2014
Actual Primary Completion Date : September 11, 2018
Actual Study Completion Date : September 11, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Psoriasis
Drug Information available for: Ustekinumab

Arm Intervention/treatment
Active Comparator: Ustekinumab (Stelara)
Ustekinumab (Stelara) subcutaneous injection 45mg (if person's weight is 100kg or less) or 90mg (if person's weight is greater than 100kg) at day 0 and week 4 followed by every 12-week dosing thereafter. Patient will receive total of 52 weeks of ustekinumab (12 weeks during RCT phase, 40 weeks post RCT phase). The end of study is at Week 52 for this arm.
Drug: Ustekinumab
Placebo Comparator: Placebo
Placebo subcutaneous injection will be given according to the same dose and schedule as the active comparator until week 12 (end of RCT phase). At week 12, ustekinumab will be administered according according to the same injection schedule as the active comparator arm for 52 weeks. Patient will receive total of 52 weeks of ustekinumab (0 weeks during RCT phase, 52 weeks post RCT phase). The end of study is at Week 64 for this arm.
Drug: Ustekinumab
Drug: Placebo



Primary Outcome Measures :
  1. Change in Vascular Inflammation [ Time Frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) ]
    Change in total vascular inflammation of five aortic segments as assessed on FDG-PET/CT between baseline and week 12 (RCT period) or end of study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period). The arterial uptake of FDG is measured by the standardized uptake value (SUV) max divided by the venous SUV mean yielding a target to background ratio (TBR).

  2. Change in Inflammatory Biomarker Levels: Intercellular Adhesion Molecule-1 (ICAM-1) [ Time Frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) ]
    To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on ICAM-1, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).

  3. Change in Inflammatory Biomarker Levels: Vascular Cell Adhesion Molecule-1 (VCAM-1) [ Time Frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) ]
    To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on VCAM-1, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).

  4. Change in Inflammatory Biomarker Levels: C-reactive Protein (CRP) [ Time Frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) ]
    To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on CRP, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).

  5. Change in Inflammatory Biomarker Levels: Ferritin [ Time Frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) ]
    To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Ferritin, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).

  6. Change in Inflammatory Biomarker Levels: Serum Amyloid A (SAA) [ Time Frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) ]
    To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on SAA, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).

  7. Change in Inflammatory Biomarker Levels: Interferon-gamma (INF-g) [ Time Frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) ]
    To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on INF-g,, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).

  8. Change in Inflammatory Biomarker Levels: Monocyte Chemoattractant Protein-1 (MCP-1) [ Time Frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) ]
    To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on MCP-1, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).

  9. Change in Inflammatory Biomarker Levels: Tumor Necrosis Factor-alpha (TNF-a) [ Time Frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) ]
    To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on TNF-a, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).

  10. Change in Inflammatory Biomarker Levels: GlycA [ Time Frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) ]
    To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on GlycA, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).

  11. Change in Inflammatory Biomarker Levels: Interleukin (IL)-1b [ Time Frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) ]
    To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on IL-1b, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).

  12. Change in Inflammatory Biomarker Levels: IL-2ra [ Time Frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) ]
    To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on IL-2ra, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).

  13. Change in Inflammatory Biomarker Levels: IL-12/23 [ Time Frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) ]
    To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on IL-12/23, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).

  14. Change in Inflammatory Biomarker Levels: IL-17a [ Time Frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) ]
    To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on IL-17a, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).

  15. Change in Inflammatory Biomarker Levels: IL-18 [ Time Frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) ]
    To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on IL-18, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).

  16. Change in Inflammatory Biomarker Levels: IL-6 [ Time Frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) ]
    To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on IL-6, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).

  17. Change in Inflammatory Biomarker Levels: IL-8 [ Time Frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) ]
    To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on IL-8, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).

  18. Change in Lipid Biomarker Levels: Triglycerides [ Time Frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) ]
    To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Triglycerides, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).

  19. Change in Lipid Biomarker Levels: Total Cholesterol [ Time Frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) ]
    To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Total cholesterol, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).

  20. Change in Lipid Biomarker Levels: High-density Lipoprotein (HDL) Cholesterol [ Time Frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) ]
    To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on HDL cholesterol, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).

  21. Change in Lipid Biomarker Levels: HDL Particle Number [ Time Frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) ]
    To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on HDL particle number, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).

  22. Change in Lipid Biomarker Levels: HDL Particle Size [ Time Frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) ]
    To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on HDL particle size, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).

  23. Change in Lipid Biomarker Levels: Large-HDL Particle Number [ Time Frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) ]
    To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Large-HDL particle number, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).

  24. Change in Lipid Biomarker Levels: Small-HDL Particle Number [ Time Frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) ]
    To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Small-HDL particle number, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).

  25. Change in Lipid Biomarker Levels: Medium-HDL Particle Number [ Time Frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) ]
    To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Medium-HDL particle number, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).

  26. Change in Lipid Biomarker Levels: Large Medium-HDL Particle Number [ Time Frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) ]
    To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Large medium-HDL particle number, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).

  27. Change in Lipid Biomarker Levels: Low-density Lipoprotein (LDL) Cholesterol [ Time Frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) ]
    To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on LDL cholesterol, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).

  28. Change in Lipid Biomarker Levels: LDL Particle Number [ Time Frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) ]
    To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on LDL particle number, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).

  29. Change in Lipid Biomarker Levels: LDL Particle Size [ Time Frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) ]
    To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on LDL particle size, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).

  30. Change in Lipid Biomarker Levels: Small-LDL Particle Number [ Time Frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) ]
    To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Small-LDL particle number, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).

  31. Change in Lipid Biomarker Levels: Large-LDL Particle Number [ Time Frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) ]
    To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Large-LDL particle number, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).

  32. Change in Lipid Biomarker Levels: Very Large-LDL Particle Number [ Time Frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) ]
    To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Very large-LDL particle number, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).

  33. Change in Lipid Biomarker Levels: Very Low-density Lipoprotein (VLDL) Particle Size [ Time Frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) ]
    To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on VLDL particle size, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).

  34. Change in Lipid Biomarker Levels: VLDL Particle Number [ Time Frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) ]
    To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on VLDL particle number, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).

  35. Change in Lipid Biomarker Levels: VLDL Triglycerides [ Time Frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) ]
    To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on VLDL triglycerides, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).

  36. Change in Lipid Biomarker Levels: Small-VLDL Particle Number [ Time Frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) ]
    To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Small-VLDL particle number, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).

  37. Change in Lipid Biomarker Levels: Medium-VLDL Particle Number [ Time Frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) ]
    To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Medium-VLDL particle number, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).

  38. Change in Lipid Biomarker Levels: Large Medium-VLDL Particle Number [ Time Frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) ]
    To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Large medium-VLDL particle number, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).

  39. Change in Lipid Biomarker Levels: Large-VLDL Particle Number [ Time Frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) ]
    To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Large-VLDL particle number, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).

  40. Change in Lipid Biomarker Levels: Intermediate-density Lipoprotein (IDL) Particle Number [ Time Frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) ]
    To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on IDL particle number, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).

  41. Change in Lipid Biomarker Levels: Cholesterol Efflux Capacity [ Time Frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) ]

    To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Cholesterol efflux capacity, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).

    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)].


  42. Change in Lipid Biomarker Levels: Apolipoprotein-B [ Time Frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) ]
    To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Apolipoprotein-B, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).

  43. Change in Lipid Biomarker Levels: Fetuin-A [ Time Frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) ]
    To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Fetuin-A, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).

  44. Change in Metabolic Biomarker Levels: Adiponectin [ Time Frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) ]
    To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Adiponectin, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).

  45. Change in Metabolic Biomarker Levels: Leptin [ Time Frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) ]
    To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Leptin, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).

  46. Change in Metabolic Biomarker Levels: Insulin [ Time Frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) ]
    To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Insulin, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).

  47. Change in Metabolic Biomarker Levels: Glucose [ Time Frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) ]
    To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on Glucose, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).

  48. Change in Metabolic Biomarker Levels: Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) [ Time Frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) ]

    To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on HOMA-IR, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).

    HOMA-IR, a method used to quantify insulin resistance and beta-cell function, is expressed using fasting blood glucose and insulin levels. It is calculated using the formula (HOMA-IR = fasting glucose [mg/dl] * fasting insulin [mU/ml]/405).



Secondary Outcome Measures :
  1. Number of Participants Achieving PASI75 (75% or Greater Reduction in PASI Score) [ Time Frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) ]

    To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on PASI75, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).

    Binary measure of change in psoriasis activity; 75% or greater reduction in PASI score compared to baseline.


  2. Number of Participants Achieving PASI90 (90% or Greater Reduction in PASI Score) [ Time Frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) ]

    To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on PASI90, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).

    Binary measure of change in psoriasis activity; 90% or greater reduction in PASI score compared to baseline.


  3. Number of Participants Achieving Physician Global Assessment (PGA) Clear/Almost Clear [ Time Frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) ]

    To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on PGA clear/almost clear, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).

    Binary measure of psoriasis disease activity at measurement time points; Physician Global Assessment score <1.5 (clear/almost clear)


  4. Change in Patient-Reported Outcomes: MEDFICTS [ Time Frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) ]

    To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on MEDFICTS, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).

    MEDFICTS (Meats, Eggs, Dairy, Fried foods, fat In baked goods, Convenience foods, fats added at the Table, and Snacks), a brief dietary assessment instrument, has been provided as part of the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) guidelines as a free tool to use for proper cardiovascular diet assessment. The questionnaire yields a continuous score (ranging from 0 to 216), with a score of <40 indicating adherence to the Therapeutic Lifestyle Changes (TLC) diet (intake of <7% of energy from saturated fat, <30% of energy from total fat, and <200 mg dietary cholesterol/day).


  5. Change in Patient-reported Physical Activity Assessments: IPAQ [ Time Frame: Baseline - Week 12; Baseline - End of Study Visit (Week 52 or Week 64) ]

    To assess the effects of ustekinumab, as compared to placebo, at Week 12 (RCT period) in patients with moderate to severe psoriasis on IPAQ, and assess global change at end study (Week 52 for Ustekinumab arm, Week 64 for Placebo arm; active treatment period).

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




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.


Layout table for eligibility information
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. 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 score of ≥ 12 at the Baseline (Week 0) visit.
  6. Subject is a candidate for systemic therapy 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 periodic pregnancy testing during the study and agree to use at least one method of contraception throughout the study duration and for at least 15 weeks after the last dose of the study drug 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.
  8. Men are eligible to participate in the study if they meet one of the following criteria:

    1. Agree to use a proven birth control method during the study and for at least 15 weeks after the last dose of the study drug.
    2. Have a female partner who agrees to use at least one method of contraception throughout the study duration and for at least 15 weeks after the last dose of the study drug.
    3. Have a female partner who is postmenopausal (for at least one year), sterile, or hysterectomized;
    4. Have a female partner who has undergone tubal ligation,
    5. Agree to be sexually abstinent, defined as total abstinence from sexual intercourse, as a form of contraception.
  9. 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.
  10. 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 an IL-12/IL-23 antagonist that led to discontinuation of therapy and contraindicates future treatment.
  2. Previous lack of response to an IL-12/IL-23 antagonist that led to discontinuation of therapy.
  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 or Excimer laser for at least 14 days prior to the Baseline (Week 0) visit and during the study.
  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 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).
      • Any IL-12/IL-23 antagonist (e.g., ustekinumab, briakinumab) 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, cerebrovascular accident or myocardial infarction within the prior 6 months, 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 with the exception 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. 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 positive Quantiferon-GOLD result; 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 within 3 years prior to the first administration of study agent.
    • Any other significant infection requiring hospitalization or intravenous (IV) antibiotics in the month prior to Baseline;
    • Infection requiring treatment with oral or parenteral (other than IV) antibiotics within 14 days prior to Baseline;
    • Subject has received vaccination with Bacille Calmette-Guerin (BCG) within 365 days prior to Screening or will receive BCG vaccination during study participation including up to 12 months after the last dose of the study drug;
    • 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 3 months after the last dose of study drug.
  13. 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.
  14. Female subject who is pregnant or breast-feeding or considering becoming pregnant during the study.
  15. Male subject who is considering fathering a child 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 109/L and absolute neutrophil count (ANC) is >1000 cells / mm3.

    • WBC count > 15 x 109/L;
    • Platelet count < 100 x 109/L;
    • Serum creatinine >1.6 mg/dL (>141 µmol/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)
  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.

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): NCT02187172


Locations
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United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
University of Pennsylvania
Janssen Scientific Affairs, LLC
Investigators
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Principal Investigator: Joel M Gelfand, MD, MSCE University of Pennsylvania
  Study Documents (Full-Text)

Documents provided by University of Pennsylvania:
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Responsible Party: University of Pennsylvania
ClinicalTrials.gov Identifier: NCT02187172    
Other Study ID Numbers: 820124
First Posted: July 10, 2014    Key Record Dates
Results First Posted: August 15, 2019
Last Update Posted: August 15, 2019
Last Verified: August 2019
Keywords provided by University of Pennsylvania:
Psoriasis
Cardiovascular Disease
Vascular Inflammation
Lipid Biomarkers
FDG-PET/CT
Additional relevant MeSH terms:
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Cardiovascular Diseases
Psoriasis
Inflammation
Pathologic Processes
Skin Diseases, Papulosquamous
Skin Diseases
Ustekinumab
Dermatologic Agents