Clinical trial NCT01088165: The Influence of Adalimumab on Cardiovascular and Metabolic Risk in Psoriasis
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Psoriasis
Cardiovascular Diseases
Diabetes Mellitus, Type 2
Keywords: Psoriasis
Cardiovascular Diseases
Diabetes Mellitus, Type 2
Adalimumab
Fumaric acid esters
Lead sponsor: Medical University of Vienna
Sponsor class: OTHER
First posted: 2010-03-17
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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


Eligibility criteria: 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

Primary outcomes:
measure: 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)
timeFrame: 3 and 6 months
Secondary outcomes:
measure: 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
timeFrame: 3 and 6 months
measure: Influence of adalimumab in comparison to fumaric acid esters on biochemical cardiovascular and metabolic risk factors
timeFrame: 3 and 6 months
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Medical University Vienna Dpt. of Dermatology
Study officials:
affiliation: Medical University of Vienna Department of Dermatology
name: Adrian Tanew, MD
role: PRINCIPAL_INVESTIGATOR
References: