Vascular Inflammation in Psoriasis Trial (The VIP Trial)

NCT ID: NCT01553058

Last Updated: 2018-05-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 97 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-07-31
• Study Completion Date: 2016-10-27

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Adalimumab (Humira)

Injection of the active drug Humira.

Group Type: ACTIVE_COMPARATOR

Adalimumab (Humira)

Intervention Type: 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.

Placebo Injection

Injection of placebo in place of active Humira injection.

Group Type: PLACEBO_COMPARATOR

Placebo Injection

Intervention Type: DRUG

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

NB-UVB phototherapy

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

Group Type: ACTIVE_COMPARATOR

NB-UVB phototherapy

Intervention Type: OTHER

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

Interventions

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.

Intervention Type: DRUG

Placebo Injection

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

Intervention Type: DRUG

NB-UVB phototherapy

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

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Males and females 18 years of age and older.

2. Clinical diagnosis of psoriasis for at least 6 months as determined by subject interview of his/her medical history and confirmation of diagnosis through physical examination by Investigator.

3. Stable plaque psoriasis for at least 2 months before Screening and at Baseline (Week 0) as determined by subject interview of his/her medical history.

4. Moderate to severe psoriasis defined by ≥ 10 percent Body Surface Area (BSA) involvement at the Baseline (Week 0) visit.

5. PASI (psoriasis assessment and severity index) score of ≥ 12 at the Baseline (Week 0) visit.

6. Subject is a candidate for systemic therapy or phototherapy and has active psoriasis despite prior treatment with topical agents.

7. Women are eligible to participate in the study if they meet one of the following criteria:

1. Women of childbearing potential who are willing to undergo regular pregnancy testing and agree to use one method of contraception throughout the study are eligible to participate

2. Women who are postmenopausal (for at least one year), sterile, or hysterectomized are eligible to participate

3. Women who have undergone tubal ligation are eligible to participate

4. Women who agree to be sexually abstinent, defined as total abstinence from sexual intercourse, as a form of contraception are eligible to participate in the study.

8. Subject is judged to be in good general health as determined by the Principal Investigator based upon the results of medical history, laboratory profile, physical examination, and 12-lead electrocardiogram (ECG) performed at screening.

9. Able and willing to give written informed consent and to comply with requirements of this study protocol.

Exclusion Criteria

1. Previous adverse event following exposure to a TNF-alpha antagonist and/or UV phototherapy that led to discontinuation of either of these therapies and contraindicates future treatment.

2. Previous lack of response to a TNF-alpha antagonist and/or UV phototherapy that led to discontinuation of either of these therapies.

3. Diagnosis of erythrodermic psoriasis, generalized or localized pustular psoriasis, medication-induced or medication-exacerbated psoriasis, or new onset guttate psoriasis.

4. Diagnosis of other active skin diseases or skin infections (bacterial, fungal, or viral) that may interfere with evaluation of psoriasis.

5. Cannot avoid UVB phototherapy for at least 14 days prior to the Baseline (Week 0) visit.

6. Cannot avoid psoralen-UVA phototherapy for at least 30 days prior to the Baseline (Week 0) visit and during the study.

7. Cannot discontinue systemic therapies for the treatment of psoriasis, or systemic therapies known to improve psoriasis, during the study:

• Systemic (investigational or marketed) therapies must be discontinued at least 30 days prior to the Baseline (Week 0) visit except for biologics.

• All biologics, except ustekinumab, must be discontinued for at least 90 days prior to Baseline (Week 0).
• The IL-12/IL-23 antagonist ustekinumab (half-life of 45.6 ± 80.2 days) must be discontinued for at least 180 days prior to Baseline (Week 0).
• Investigational agents must be discontinued at least 30 days or 5 half-lives (whichever is longer) prior to the Baseline (Week 0) visit.

8. Subject is taking or requires oral or injectable corticosteroids during the study. Inhaled corticosteroids for stable medical conditions are allowed.

9. Poorly controlled medical condition, such as unstable ischemic heart disease, congestive heart failure, recent cerebrovascular accidents, psychiatric disease requiring frequent hospitalization, and any other condition, which, in the opinion of the Investigator, would put the subject at risk by participation in the study.

10. History of diabetes mellitus, type 1 or type 2 - note that patients with type 2 diabetes may be enrolled if the duration of diabetes is <10 years and HbA1c is <7.0%)

11. Uncontrolled hypertension, with measured systolic blood pressure >180 mmHg or diastolic blood pressure >90 mmHg

12. History of demyelinating diseases or lupus.

13. Subject has infection or risk factors for severe infections, for example:

• Positive serology or known history of HIV, hepatitis B or C, or other severe, recurrent, or persistent infections;
• Excessive immunosuppression or other factors associated with it, including human immunodeficiency virus infection;
• Active tuberculosis (TB) disease;
• Evidence of latent TB infection demonstrated by Purified Protein Derivative (PPD) ≥ 5 mm of induration or positive Quantiferon-GOLD results; except if prophylactic treatment for TB, as recommended by local guidelines, is initiated prior to administration of study drug or if there is documentation that the subject has received prophylactic treatment for TB previously.
• Any other significant infection requiring hospitalization or intravenous (IV) antibiotics in the month prior to Baseline;
• Infection requiring treatment with oral or parenteral antibiotics within 14 days prior to Baseline;
• Subject has received vaccination with Bacille Calmette-Guerin (BCG) within 365 days prior to Screening;
• Subject has received vaccination with a live viral agent 30 days prior to Screening or will require a live vaccination during study participation including up to 30 days after the last dose of study drug.

14. Subject has history of hematological or solid malignancy other than successfully treated basal cell carcinoma, non-metastatic cutaneous squamous cell carcinoma or cervical carcinoma in situ.

15. Female subject who is pregnant or breast-feeding or considering becoming pregnant during the study.

16. Screening clinical laboratory analyses showing any of the following abnormal results:

• Hemoglobin (Hgb) < 10 g/dL in females or <12 g/dL in males;
• White blood cell (WBC) count <2.5 x 109/L

o Subject can be included if WBC count is <2.5 x x 109/L and absolute neutrophil count (ANC) is >1000 cells / mm3.

• WBC count > 15 x 109/L;
• Platelet count < 100 x 109/L;
• Serum aspartate transaminase (AST) or alanine transaminase (ALT) >2.5 upper limits of normal (ULN);
• Serum total bilirubin ≥2 mg/dL (≥26 µmol/L); or
• Serum creatinine >1.6 mg/dL (>141 µmol/L).

17. Recent history of substance abuse or psychiatric illness that could preclude compliance with the protocol.

18. History of any substance abuse within 365 days of screening visit

19. Alcohol use >14 drinks per week at the screening visit or within 30 days of the screening period

20. If subject is on cholesterol-lowering medication (e.g. statin), dose and form of medication must be stable for 90 days prior to week 0 and remain stable throughout the duration of the study.

21. History of photosensitivity of medical condition that may be exacerbated by UV exposures such as lupus or dermatomyositis

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Pennsylvania

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Joel Gelfand, MD MSCE

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Locations

University of California, Davis Health System

Sacramento, California, United States

The University of Colorado

Denver, Colorado, United States

National Heart, Lung, and Blood Institute

Bethesda, Maryland, United States

Buffalo Medical Group

Buffalo, New York, United States

Oregon Health & Science University

Portland, Oregon, United States

The University of Pennsylvania

Philadelphia, Pennsylvania, United States

Menter Dermatology Research Institute

Dallas, Texas, United States

Center for Clinical Studies

Houston, Texas, United States

University of Utah

Salt Lake City, Utah, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 31163241 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29776990 (View on PubMed)

Other Identifiers

814278

Identifier Type: -

Identifier Source: org_study_id