The Influence of Adalimumab on Cardiovascular and Metabolic Risk in Psoriasis

NCT01088165 | Unknown Phase 4

• 1 other identifier: CASTIP1
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

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

Keywords

Psoriasis; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Adalimumab; Fumaric acid esters

Outcome Measures

Primary Outcomes (1)

• 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)

  3 and 6 months

Secondary Outcomes (2)

• 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

  3 and 6 months

• Influence of adalimumab in comparison to fumaric acid esters on biochemical cardiovascular and metabolic risk factors

  3 and 6 months

Study Arms (2)

Adalimumab treatment group

EXPERIMENTAL

Drug: Adalimumab treatment arm; Other: Narrow band UVB radiation

Fumaric acid esters treatment group

ACTIVE COMPARATOR

Drug: Fumaric acid esters treatment group; Other: Narrow band UVB radiation

Interventions

Adalimumab treatment arm DRUG

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

Also known as: Humira, Adalimumab

Adalimumab treatment group

Fumaric acid esters treatment group 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.

Also known as: Fumaderm

Fumaric acid esters treatment group

Narrow band UVB radiation 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

Adalimumab treatment group; Fumaric acid esters treatment group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Medical University of Vienna: lead

Study Sites (1)

Medical University Vienna Dpt. of Dermatology

Vienna, 1090, Austria

RECRUITING

MeSH Terms

Conditions

Psoriasis; Cardiovascular Diseases; Diabetes Mellitus, Type 2

Interventions

Adalimumab; Dimethyl Fumarate

Condition Hierarchy (Ancestors)

Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Fumarates; Dicarboxylic Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals

Study Officials

• Adrian Tanew, MD

  Medical University of Vienna Department of Dermatology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gregor Holzer, MD

CONTACT

40400; gregor.holzer@meduniwien.ac.at

Adrian Tanew, MD

CONTACT

40400; adrian.tanew@meduniwien.ac.at

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr

Study Record Dates

• First Submitted: March 16, 2010
• First Posted: March 17, 2010
• Study Start: May 1, 2010
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2014
• Last Updated: January 20, 2012

Record last verified: 2012-01

Locations

AU (1)