Vascular Inflammation in Psoriasis Trial (The VIP Trial)

NCT01553058 | Completed Phase 4 Results DMC

• 1 other identifier: 814278
• Study Type: interventional
• Target: 97
• Locations: 1 country
• Sites: 9

Brief 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.

Conditions

Psoriasis; Cardiovascular Disease

Keywords

Psoriasis; Cardiovascular Disease; FDG/PET-CT; NB-UVB Phototherapy; Vascular Inflammation; Lipid Biomarkers

Outcome Measures

Primary Outcomes (12)

• Change in Vascular Inflammation

  Change in total vascular inflammation of five aortic segments as assessed on FDG-PET/CT between baseline and week 12. 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).

  Baseline - Week 12

• Change in Cardiometabolic Biomarkers: Total Cholesterol

  To assess the effects of adalimumab, as compared to NB-UVB phototherapy or placebo, in patients with moderate to severe psoriasis on total cholesterol.

  Baseline - Week 12

• Change in Cardiometabolic Biomarkers: Cholesterol Efflux

  To assess the effects of adalimumab, as compared to NB-UVB phototherapy or placebo, in patients with moderate to severe psoriasis on cholesterol efflux capacity. 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: \[(µCi of 3H-cholesterol in media containing apoB-depleted subject plasma - µCi of 3H-cholesterol in plasma-free media) / (µCi of 3H-cholesterol in media containing apoB-depleted pooled control plasma-µCi of 3H-cholesterol in pooled control plasma-free media)\]. The pooled plasma was obtained from five healthy volunteers.

  Baseline - Week 12

• Change in Cardiometabolic Biomarkers: Low Density Lipoprotein Particle Total

  To assess the effects of adalimumab, as compared to NB-UVB phototherapy or placebo, in patients with moderate to severe psoriasis on low density lipoprotein particle total.

  Baseline - Week 12

• Change in Cardiometabolic Biomarkers: High Density Lipoprotein Particle Total

  To assess the effects of adalimumab, as compared to NB-UVB phototherapy or placebo, in patients with moderate to severe psoriasis on high density lipoprotein particle total.

  Baseline - Week 12

• Change in Cardiometabolic Biomarkers: Log Insulin

  To assess the effects of adalimumab, as compared to NB-UVB phototherapy or placebo, in patients with moderate to severe psoriasis on log insulin.

  Baseline - Week 12

• Change in Cardiometabolic Biomarkers: Log Adiponectin

  To assess the effects of adalimumab, as compared to NB-UVB phototherapy or placebo, in patients with moderate to severe psoriasis on log adiponectin.

  Baseline - Week 12

• Change in Cardiometabolic Biomarkers: Log Leptin

  To assess the effects of adalimumab, as compared to NB-UVB phototherapy or placebo, in patients with moderate to severe psoriasis on log leptin.

  Baseline - Week 12

• Change in Cardiometabolic Biomarkers: Log C-reactive Protein

  To assess the effects of adalimumab, as compared to NB-UVB phototherapy or placebo, in patients with moderate to severe psoriasis on log C-reactive protein (CRP).

  Baseline - Week 12

• Change in Cardiometabolic Biomarkers: Log Tumor Necrosis Factor-alpha

  To assess the effects of adalimumab, as compared to NB-UVB phototherapy or placebo, in patients with moderate to severe psoriasis on log Tumor necrosis factor-alpha.

  Baseline - Week 12

• Change in Cardiometabolic Biomarkers: Log Interleukin 6

  To assess the effects of adalimumab, as compared to NB-UVB phototherapy or placebo, in patients with moderate to severe psoriasis on log interleukin 6.

  Baseline - Week 12

• Change in Cardiometabolic Biomarkers: GlycA

  To assess the effects of adalimumab, as compared to NB-UVB phototherapy or placebo, in patients with moderate to severe psoriasis on GlycA

  Baseline - Week 12

Secondary Outcomes (6)

• Change in Psoriasis Activity (PASI-75 and PGA)

  Baseline - Week 12

• Change in Patient-reported Outcomes-EuroQol EQ-5D

  Baseline -Week 12

• Change in Patient-reported Outcomes-Dermatology Life Quality Index (DLQI)

  Baseline - Week 12

• Change in Patient-reported Outcomes-MEDFICTS Dietary Assessment)

  Baseline to Week 12

• Change in Patient-reported Outcomes-International Physical Activity Questionnaire (IPAQ)

  Baseline week 4, 8 and 12

Study Arms (3)

Adalimumab (Humira)

ACTIVE COMPARATOR

Injection of the active drug Humira.

Drug: Adalimumab (Humira)

Placebo Injection

PLACEBO COMPARATOR

Injection of placebo in place of active Humira injection.

Drug: Placebo Injection

NB-UVB phototherapy

ACTIVE COMPARATOR

NB-UVB Phototherapy 3 times per week, no other intervention.

Other: NB-UVB phototherapy

Interventions

Adalimumab (Humira) DRUG

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.

Adalimumab (Humira)

Placebo Injection DRUG

Placebo injection will be given according to the same dose and schedule as the active comparator.

Placebo Injection

NB-UVB phototherapy OTHER

Phototherapy will be given 3 times per week according to the Fitzpatrick scale for skin types.

NB-UVB phototherapy

Eligibility Criteria

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

You may qualify if:

• Males and females 18 years of age and older.
• 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.
• 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.
• Moderate to severe psoriasis defined by ≥ 10 percent Body Surface Area (BSA) involvement at the Baseline (Week 0) visit.
• PASI (psoriasis assessment and severity index) score of ≥ 12 at the Baseline (Week 0) visit.
• Subject is a candidate for systemic therapy or phototherapy and has active psoriasis despite prior treatment with topical agents.
• Women are eligible to participate in the study if they meet one of the following criteria:
• 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
• Women who are postmenopausal (for at least one year), sterile, or hysterectomized are eligible to participate
• Women who have undergone tubal ligation are eligible to participate
• 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.
• 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.
• Able and willing to give written informed consent and to comply with requirements of this study protocol.

You may not qualify if:

• 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.
• Previous lack of response to a TNF-alpha antagonist and/or UV phototherapy that led to discontinuation of either of these therapies.
• Diagnosis of erythrodermic psoriasis, generalized or localized pustular psoriasis, medication-induced or medication-exacerbated psoriasis, or new onset guttate psoriasis.
• Diagnosis of other active skin diseases or skin infections (bacterial, fungal, or viral) that may interfere with evaluation of psoriasis.
• Cannot avoid UVB phototherapy for at least 14 days prior to the Baseline (Week 0) visit.
• Cannot avoid psoralen-UVA phototherapy for at least 30 days prior to the Baseline (Week 0) visit and during the study.
• 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.
• Subject is taking or requires oral or injectable corticosteroids during the study. Inhaled corticosteroids for stable medical conditions are allowed.
• 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.
• 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%)
• Uncontrolled hypertension, with measured systolic blood pressure \>180 mmHg or diastolic blood pressure \>90 mmHg

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (9)

University of California, Davis Health System

Sacramento, California, 95816, United States

Location

The University of Colorado

Denver, Colorado, 80045, United States

Location

National Heart, Lung, and Blood Institute

Bethesda, Maryland, 20892, United States

Location

Buffalo Medical Group

Buffalo, New York, 14221, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

The University of Pennsylvania

Philadelphia, Pennsylvania, 19140, United States

Location

Menter Dermatology Research Institute

Dallas, Texas, 75246, United States

Location

Center for Clinical Studies

Houston, Texas, 77004, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Related Publications (2)

• Noe MH, Wan MT, Shin DB, Armstrong AW, Duffin KC, Chiesa Fuxench ZC, Kalb RE, Menter A, Simpson EL, Takeshita J, Tyring SK, Van Voorhees AS, Mehta NN, Gelfand JM. Patient-reported outcomes of adalimumab, phototherapy, and placebo in the Vascular Inflammation in Psoriasis Trial: A randomized controlled study. J Am Acad Dermatol. 2019 Oct;81(4):923-930. doi: 10.1016/j.jaad.2019.05.080. Epub 2019 Jun 1.

  PMID: 31163241 DERIVED

• Mehta NN, Shin DB, Joshi AA, Dey AK, Armstrong AW, Duffin KC, Fuxench ZC, Harrington CL, Hubbard RA, Kalb RE, Menter A, Rader DJ, Reilly MP, Simpson EL, Takeshita J, Torigian DA, Werner TJ, Troxel AB, Tyring SK, Vanderbeek SB, Van Voorhees AS, Playford MP, Ahlman MA, Alavi A, Gelfand JM. Effect of 2 Psoriasis Treatments on Vascular Inflammation and Novel Inflammatory Cardiovascular Biomarkers: A Randomized Placebo-Controlled Trial. Circ Cardiovasc Imaging. 2018 Jun;11(6):e007394. doi: 10.1161/CIRCIMAGING.117.007394.

  PMID: 29776990 DERIVED

MeSH Terms

Conditions

Psoriasis; Cardiovascular Diseases

Interventions

Adalimumab

Condition Hierarchy (Ancestors)

Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Suzette Baez VanderBeek, MPH
• Organization: University of Pennsylvania

suzettev@upenn.edu

215-662-3514

Study Officials

• Joel Gelfand, MD MSCE

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2012
• First Posted: March 13, 2012
• Study Start: July 1, 2012
• Primary Completion: August 8, 2016
• Study Completion: October 27, 2016
• Last Updated: May 22, 2018
• Results First Posted: May 22, 2018

Record last verified: 2018-04

Locations

US (9)