Comparison of the bacterial microbiota in the skin and gut of psoriasis patients before and after sytemic treatment with adalimumab and ustekinumab or cyclosporin

Organizational Data

DRKS-ID:
DRKS00007147
Recruitment Status:
Recruiting complete, study complete
Date of registration in DRKS:
2015-03-31
Last update in DRKS:
2023-01-04
Registration type:
Prospective

Acronym/abbreviation of the study

MIPSO

URL of the study

No Entry

Brief summary in lay language

The aim of this study is to investigate the treatment effects of different drugs (adalimumab, ustekinumab and cyclosporine) on the presence of microorganisms (e.g.bacteria) in skin and in stool in adult patients with psoriasis vulgaris. During the study period, which extends over a total of about 24 weeks, swabs from skin, biopsies from skin and stool samples will be taken repeatedly.

Brief summary in scientific language

Change in the composition of the cutaneous microbiota in lesional skin of psoriasis patients after systemic treatment with adalimumab, ustekinumab or cyclosporine (baseline versus 4 weeks after start of treatment).

Health condition or problem studied

Free text:
MedDRA - Psoriasis vulgaris (10050576)
ICD10:
L40.0 - Psoriasis vulgaris
Healthy volunteers:
No Entry

Interventions, Observational Groups

Arm 1:
Stelara® (ustekinumab) 45 mg resp. 90 mg s.c. Day 0, 28 and 112
Arm 2:
Humira® (Adalimumab) 80 mg s.c. Day 0, 40 mg s.c. Day 8 and then every 2 weeks
Arm 3:
Cyclosporine capsules oral, dosage according to the AWMF-Guidelines for Psoriasis vulgaris

Endpoints

Primary outcome:
Comparison of the differences in the relative frequencies of microorganisms in lesional skin of psoriasis patients before treatment with adalimumab, ustekinumab or cyclosporine versus 4 weeks after start of treatment by use of DNA sequence analysis.
Secondary outcome:
- Comparison of the differences in the relative frequencies of the microorganisms in lesional skin of psoriasis patients treated with adalimumab, ustekinumab or cyclosporine, over the entire study period. - Comparison of the differences in the relative frequencies of intestinal microorganisms in psoriasis patients treated with adalimumab, ustekinumab or cyclosporine, over the entire study period. - Correlation of the differences in the relative frequencies of the microorganisms in lesional skin of psoriasis patients treated with adalimumab, ustekinumab or cyclosporine, with PASI and BSA ​​over the entire study period. - Correlation of the differences in the relative frequencies of the intestinal microorganisms of psoriasis patients treated with adalimumab, ustekinumab or cyclosporine, with PASI and BSA ​​over the entire study period. - Comparison of the differences in the phenotypic modifications of microorganisms in lesional skin of psoriasis patients treated with adalimumab, ustekinumab or cyclosporine, over the entire study period, after a correlation of phylogenetic modifications and clinical parameters (PASI, BSA) could be detected. - Comparison of the differences in the phenotypic modifications of intestinal microorganisms in psoriasis patients treated with adalimumab, ustekinumab or cyclosporine, over the entire study period, after a correlation of phylogenetic modifications and clinical parameters (PASI, BSA) could be detected.

Study Design

Purpose:
Diagnostic
Allocation:
Non-randomized controlled study
Control:
  • Active control (effective treatment of control group)
Phase:
IV
Study type:
Interventional
Mechanism of allocation concealment:
No Entry
Blinding:
No
Assignment:
Parallel
Sequence generation:
No Entry
Who is blinded:
No Entry

Recruitment

Recruitment Status:
Recruiting complete, study complete
Reason if recruiting stopped or withdrawn:
No Entry

Recruitment Locations

Recruitment countries:
  • Germany
Number of study centers:
Monocenter study
Recruitment location(s):
  • University medical center Klinik für Hautkrankheiten Münster

Recruitment period and number of participants

Planned study start date:
2015-04-16
Actual study start date:
2015-06-19
Planned study completion date:
No Entry
Actual Study Completion Date:
2017-09-11
Target Sample Size:
36
Final Sample Size:
37

Inclusion Criteria

Sex:
All
Minimum Age:
18 Years
Maximum Age:
no maximum age
Additional Inclusion Criteria:
Inclusion criteria for all patients: 1. Patients with at least moderate psoriasis vulgaris (plaque psoriasis) (PASI ≥ 10). 2. > 18 years (male and female). 3. Treatment according to the guidelines and standard therapies for psoriasis with adalimumab, ustekinumab or cyclosporine. Additional inclusion criteria for patients who will receive adalimumab or ustekinumab: 1.Patients with moderate or severe chronic plaque psoriasis who did not respond to other systemic therapy such as cyclosporine, methotrexate, or PUVA or patients with contraindications or intolerance to such a therapy. Additional inclusion criteria for patients who will receive cyclosporine: 1.Patients with at least moderate psoriasis vulgaris (plaque psoriasis) (PASI ≥ 10) who are not adequately treatable with conventional systemic therapy.

Exclusion Criteria

Exclusion criteria for all patients: 1.Patients treated with systemic immunosuppressives, adalimumab, etanercept, ustekinumab or infliximab within a period of 5 half-life periods of the respective drug before taking the initial skin swabs /biopsies. 2.Simultaneous therapy with systemic immunosuppressives. 3.Patients treated with antibiotics within at least 4 weeks before taking the initial skin swabs/biopsies or patients treated with antibiotics in the course of the trial with the exception of tuberculosis prophylaxis with Isoniazid. 4.Psoriasis patients who currently receive phototherapy or have received phototherapy within a period of 2 weeks before taking the initial skin swabs/biopsies 5.Patients who can not interrupt the local, topical therapy with calcineurin inhibitors or vitamin D3 analogues in skin areas chosen for the skin swabs/biopsies. Topical treatment with calcineurin inhibitors or vitamin D3 analogues may be continued in lesional skin areas that are not intended for swabs/biopsies. In skin areas chosen for the swabs/biopsies topical therapy is not allowed within 7 days before sampling. 6.Patients with relevant active infections (e.g. active tuberculosis or other severe infections such as sepsis and opportunistic infections). 7.HbsAG-positive patients. HCV-PCR-positive patients. 8.HIV-positive patients. 9.Current malignancies or history of malignancies. 10.Immunodeficient patients. 11.Patients who currently receive chemotherapy or radiotherapy or received chemotherapy or radiotherapy within the last 12 months prior to sampling of the initial skin swabs/biopsies. 12.Patients with uncontrolled chronic diseases which require continuous therapy, and which are not stable in the opinion of the investigator. 13.Patients with other chronic skin diseases such as atopic dermatitis or lupus erythematosus, which could affect the cutaneous microbiota. 14.Patients with psychiatric comorbidity, which causes deficient or missing ability for consent. 15.Participation in an another interventional trial during this trial or within 4 weeks of study entry or within 5 half-life periods of the prior investigational drug according to which period is longer. 16.Pregnancy or lactation. Women of childbearing potential or men with female partners of childbearing potential: Unwilling to agree to use reliable contraceptive methods (Pearl index < 1) during the trial and in addition to it at least 15 weeks after termination of therapy with Stelara® and at least 5 months after termination of therapy with Humira®. 17.Evidence of MRSA within 6 months before taking the initial skin swabs/biopsies. 18.Patients with psoriasis vulgaris exlusively located in the area of the head. Additional exclusion criteria for patients who will receive adalimumab: 1.Allergy to adalimumab or the other excipients of Humira®. 2.Heart failure NYHA III° or IV°. 3.Preexisting or incipient demyelinating diseases of the CNS or the PNS. 4.Simultaneous therapy with anakinra or abatacept. 5.Simultaneous vaccination with life vaccines. Vaccination with life vaccines within 5 months after the end of therapy with adalimumab. 6.Contraindications against tuberculosis prophylaxis with Isoniazid in the respective patients. Additional exclusion criteria for patients who will receive ustekinumab: 1.Allergy to ustekinumab or the other excipients of Stelara®. Allergy to latex. 2.Simultaneous vaccination with life vaccines or vaccination with life vaccines within 2 weeks of starting therapy with ustekinimab and within at least 15 weeks after the end of therapy with ustekinumab. 3.Contraindications against tuberculosis prophylaxis with Isoniazid in the respective patients. Additional exclusion criteria for patients who will receive ciclosporine: 1.Allergy to cyclosporine medication. 2.Uncontrolled arterial hypertension. 3.Uncontrolled infections. 4.Active infections with varicella including herpes zoster infections, herpes simplex infections and other viral infections (e.g. molluscs, condylomata, multiple warts). 5.Relevant renal impairment. 6.Severe hepatic disease, GOT > 2 x ULN, GPT > 2 x ULN, yGT > 2 x ULN, Bilrubin > 2 x ULN. 7.Hyperuricaemia. 8.Hyperkaliaemia. 9.History of PUVA therapie with a cumulative dose of > 1000 J/cm² 10.Therapy with etretinat within 4 weeks of starting therapy with ciclosporine. 11.Simultaneous therapy with retinoids. 12.Simultaneous therapy with coal tar. 13.Simultaneous therapy with rosuvastatin. 14.Simultaneous therapy with tacrolimus. 15.Simultaneous therapy with amber. 16.Simultaneous therapy with drugs which are substrates of the multidrug efflux transporter P-glycoprotein or of organic anion transporting polypeptides and in which increased plasma concentrations are associated with life-threatening events (e.g. bosentan, dabigatran etexilate and aliskiren). 17.Simultaneous vaccination with life vaccines. 18.Alcoholism. Contraindications to ingestion of alcohol (e.g. epilepsy). 19.Erythrodermic or pustular psoriasis. 20.Types of psoriasis which might be caused or exacerbated by drugs.

Addresses

Primary Sponsor

Address:
Universitätsklinikum Münster
Albert-Schweitzer-Campus 1, Geb. D5
48149 Münster
Germany
Telephone:
No Entry
Fax:
No Entry
Contact per E-Mail:
Contact per E-Mail
URL:
http://www.klinikum.uni-muenster.de
Investigator Sponsored/Initiated Trial (IST/IIT):
Yes

Contact for Scientific Queries

Address:
Universitätsklinikum Münster, Klinik für Hautkrankheiten
Prof. Dr. Karin Loser
Von-Esmarch-Str. 58
48149 Münster
Germany
Telephone:
0251 / 83-52953
Fax:
No Entry
Contact per E-Mail:
Contact per E-Mail
URL:
No Entry

Contact for Public Queries

Address:
Universitätsklinikum Münster, Klinik für Hautkrankheiten, Zentrale Studienkoordination für innovative Dermatologie (ZID)
Dr. med. Athanasios Tsianakas
Von-Esmarch-Str. 58
48149 Münster
Germany
Telephone:
0251 / 83-57291 oder -56558
Fax:
No Entry
Contact per E-Mail:
Contact per E-Mail
URL:
No Entry

Principal Investigator

Address:
Universitätsklinikum Münster, Klinik für Hautkrankheiten
Prof. Dr. Karin Loser
Von-Esmarch-Str. 58
48149 Münster
Germany
Telephone:
0251 / 83-52953
Fax:
No Entry
Contact per E-Mail:
Contact per E-Mail
URL:
No Entry

Sources of Monetary or Material Support

Commercial (pharmaceutical industry, medical engineering industry, etc.)

Address:
Janssen Cilag GmbH
Johnson & Johnson-Platz 1
41470 Neuss
Germany
Telephone:
No Entry
Fax:
No Entry
Contact per E-Mail:
Contact per E-Mail
URL:
No Entry

Ethics Committee

Address Ethics Committee

Address:
Ethikkommission der Ärztekammer Westfalen-Lippe und der Westfälischen Wilhelms-Universität Münster
Gartenstraße 210-214
48147 Münster
Germany
Telephone:
+49-251-9292460
Fax:
+49-251-9292478
Contact per E-Mail:
Contact per E-Mail
URL:
No Entry

Vote of leading Ethics Committee

Vote of leading Ethics Committee
Date of ethics committee application:
2014-10-27
Ethics committee number:
2014-577-f-A
Vote of the Ethics Committee:
Approved
Date of the vote:
2015-03-19

Further identification numbers

Other primary registry ID:
No Entry
EudraCT Number:
2014-003022-40
UTN (Universal Trial Number):
U1111-1159-2065
EUDAMED Number:
No Entry

IPD - Individual Participant Data

Do you plan to make participant-related data (IPD) available to other researchers in an anonymized form?:
No
IPD Sharing Plan:
No Entry

Study protocol and other study documents

Study protocols:
No Entry
Study abstract:
No Entry
Other study documents:
No Entry
Background literature:
No Entry
Related DRKS studies:
No Entry

Publication of study results

Planned publication:
No Entry
Publikationen/Studienergebnisse:
Studienergebnisse finden sich im EU Clinical Trail Register
Date of first publication of study results:
No Entry
DRKS entry published for the first time with results:
No Entry

Basic reporting

Basic Reporting / Results tables:
No Entry
Brief summary of results:
No Entry