The Influence of Adalimumab on Cardiovascular and Metabolic Risk in Psoriasis

NCT ID: NCT01088165

Last Updated: 2012-01-20

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 66 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-05-31
• Study Completion Date: 2014-05-31

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

Conditions

Psoriasis; Cardiovascular Diseases; Diabetes Mellitus, Type 2

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

Adalimumab treatment group

Group Type: EXPERIMENTAL

Adalimumab treatment arm

Intervention Type: DRUG

Adalimumab: day 1: 2x40 mg s.c., day 8: 40 mg s.c., thereafter 40 mg s.c. in biweekly intervals

Narrow band UVB radiation

Intervention Type: OTHER

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

Fumaric acid esters treatment group

Group Type: ACTIVE_COMPARATOR

Fumaric acid esters treatment group

Intervention Type: DRUG

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.

Narrow band UVB radiation

Intervention Type: OTHER

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

Interventions

Adalimumab treatment arm

Adalimumab: day 1: 2x40 mg s.c., day 8: 40 mg s.c., thereafter 40 mg s.c. in biweekly intervals

Intervention Type: 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.

Intervention Type: DRUG

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

Intervention Type: OTHER

Other Intervention Names

Humira, Adalimumab; Fumaderm

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medical University of Vienna

OTHER

Sponsor Role: lead

Responsible Party

Gregor Holzer

Dr

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Adrian Tanew, MD

Role: PRINCIPAL_INVESTIGATOR

Medical University of Vienna Department of Dermatology

Locations

Medical University Vienna Dpt. of Dermatology

Vienna, , Austria

Site Status: RECRUITING

Countries

Austria

Central Contacts

Gregor Holzer, MD

Role: CONTACT

gregor.holzer@meduniwien.ac.at

40400 ext. 7701

Adrian Tanew, MD

Role: CONTACT

adrian.tanew@meduniwien.ac.at

40400 ext. 7701

Facility Contacts

Gregor Holzer, Dr

Role: primary

gregor.holzer@meduniwien.ac.at

40400 7702

Adrian Tanew, ao Univ. Prof.

Role: backup

adrian.tanew@meduniwien.ac.at

40400 7701

Other Identifiers

CASTIP1

Identifier Type: -

Identifier Source: org_study_id