The Influence of Adalimumab on Cardiovascular and Metabolic Risk in Psoriasis (CASTIP)

January 18, 2012 updated by: Gregor Holzer, Medical University of Vienna

The Influence of Adalimumab vs. Fumaric Acid Esters on Cardiovascular and Metabolic Risk Factors in the Therapy of Patients With Moderate to Severe Psoriasis Vulgaris

Psoriasis vulgaris is no longer considered as a chronic inflammatory disease restricted to the skin. Evidence has accumulated in the past that psoriasis is a chronic inflammatory systemic disease. As in rheumatoid arthritis, the chronic inflammatory process plays a central role in the pathogenesis of associated comorbidities such as diabetes and cardiovascular disease. Since several years the armamentarium of psoriasis treatment has been broadened by the availability of TNF alpha blockers. These neutralize systemic TNF alpha which not only plays a central role in the pathogenesis of psoriasis but has also been linked to inflammatory pathways in diabetes and cardiovascular disease. While a few studies have investigated the positive effects of TNF alpha blockers on associated cardiovascular disease in rheumatoid arthritis patients, no research data exist on the effects of these therapeutic agents in patients with moderate to severe chronic plaque psoriasis.

The present study aims at determining the effects of adalimumab, a potent and frequently prescribed TNF alpha blocker for the treatment of psoriasis, on different diabetic and cardiovascular risk factors in patients receiving this treatment as a remedy for moderate to severe plaque type psoriasis. The study is designed to explore whether adalimumab is capable to prevent or modulate psoriasis-associated comorbidities by blocking systemic inflammation. The effects of adalimumab will be compared with those of fumaric acids, which represent an established traditional systemic treatment option for moderate to severe psoriasis.

Study hypothesis:

Therapy with adalimumab will lead to an improvement of several parameters that reflect the risk for diabetes and cardiovascular disease in patients with chronic plaque psoriasis due to chronic inflammation. Endothelial dysfunction, as assessed by ultrasound flow mediated dilatation, will serve as primary outcome measure. Other risk factors such as blood lipids, hsCRP, IL-6, endothelial adhesion molecules, parameters of glucose metabolism and carotid intima-media thickness will be secondary outcomes.

Aim:

If adalimumab and/or fumaric acids will show a significant impact on the above mentioned parameters, these findings would offer a new perspective for the long term management of psoriatic patients and their comorbidities.

Study design: Randomized, prospective, controlled, parallel group study

Study population: 66 patients

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

66

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Chronic severe plaque type psoriasis (PASI <10) requiring systemic treatment. Non-response or contraindication to previous systemic and/or light treatment
  • PASI ≥ 10, BSA ≥ 10
  • Age 18 - 80 years

Exclusion Criteria:

  • Women of childbearing potential not taking contraceptive measures
  • Pregnant or breastfeeding women
  • Patients with a history or ongoing malignancy, chronic infections or autoimmune disease
  • Patients with severe impairment of their general health
  • Patients who are unable to understand or comply with the study protocol

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Adalimumab treatment group
Drug: Adalimumab treatment arm
Adalimumab: day 1: 2x40 mg s.c., day 8: 40 mg s.c., thereafter 40 mg s.c. in biweekly intervals
Other Names:
  • Humira, Adalimumab
Other: Narrow band UVB radiation

No reduction of 50% minimum of baseline psoriasis severity index by week 12: additional narrow band UVB radiation, 3x/week until the patients achieve PASI reduction of 75% or greater or over a maximum period of another 12 weeks.

Initial dosage: Fitzpatrick skin phototype I and II: 0,4 J/cm2, III and IV: 0,6), 10% Increments after each radiation
ACTIVE_COMPARATOR: Fumaric acid esters treatment group
Other: Narrow band UVB radiation

No reduction of 50% minimum of baseline psoriasis severity index by week 12: additional narrow band UVB radiation, 3x/week until the patients achieve PASI reduction of 75% or greater or over a maximum period of another 12 weeks.

Initial dosage: Fitzpatrick skin phototype I and II: 0,4 J/cm2, III and IV: 0,6), 10% Increments after each radiation

Drug: Fumaric acid esters treatment group

First week:FAE mite (DIMETHYL FUMARATE 30mg, ETHYL FUMARATE CALCIUM 87mg, ETHYL FUMARATE ZINC 3mg, ETHYL FUMARATE MAGNESIUM 5mg):day 1 and 2: 0-0-1, day 3 and 4: 1-0-1, day 5-7: 1-1-1).

Week 2: FAE forte (DIMETHYL FUMARATE 120mg ETHYL, FUMARATE CALCIUM 87mg, ETHYL FUMARATE ZINC 3mg, ETHYL FUMARATE MAGNESIUM 5mg)starting with 0-0-1 capsule daily, thereafter weekly increases by on capsule until maximum daily dose 2-2-2. In the event of side effects (in particular, gastrointestinal disturbances or flushing) adaption of the dose (reduction or no increase) depending on the type and severity of the side effect will be performed. If remission occurs at a lower than the maximum dose that dose will be maintained throughout the rest of the study period.

Other Names:
  • Fumaderm

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
The influence of adalimumab treatment in comparison to treatment with fumaric acid esters on the functional integrity of the endothelium will be monitored by flow mediated dilatation (FMD)
Time Frame: 3 and 6 months
3 and 6 months

Secondary Outcome Measures

Outcome Measure
Time Frame
The measurement of carotid artery intima-media thickness (IMT) by ultrasound will serve as a morphological substrate for evaluating the potential effect of adalimumab on signs of atherosclerosis within the vessel wall
Time Frame: 3 and 6 months
3 and 6 months
Influence of adalimumab in comparison to fumaric acid esters on biochemical cardiovascular and metabolic risk factors
Time Frame: 3 and 6 months
3 and 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Medical University of Vienna

Investigators

  • Principal Investigator: Adrian Tanew, MD, Medical University of Vienna Department of Dermatology

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2010

Primary Completion (ANTICIPATED)

May 1, 2013

Study Completion (ANTICIPATED)

May 1, 2014

Study Registration Dates

First Submitted

March 16, 2010

First Submitted That Met QC Criteria

March 16, 2010

First Posted (ESTIMATE)

March 17, 2010

Study Record Updates

Last Update Posted (ESTIMATE)

January 20, 2012

Last Update Submitted That Met QC Criteria

January 18, 2012

Last Verified

January 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CASTIP1

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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