Condition category
Skin and Connective Tissue Diseases
Date applied
21/07/2010
Date assigned
15/09/2010
Last edited
13/11/2013
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

http://www.allergie-centrum-charite.de/index.php?id=1105

Contact information

Type

Scientific

Primary contact

Prof Ulrich Wahn

ORCID ID

Contact details

Department of Pediatric Pneumology and Immunology
(Klinik für Pädiatrie mit Schwerpunkt Pneumologie und Immunologie)
Charité
Augustenburger Platz 1
Berlin
13353
Germany
marina.birr@charite.de

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

Prophylaxis by Pro-Symbioflor® of atopic and allergic manifestations and activation or modulation of the immune system in newborns / small children from atopically pre-disposed parents. Prospective, randomized, placebo-controlled, double-blind parallel group trial in 632 healthy newborns aged 4 weeks with increased risk for atopic dermatitis with repeated application of Pro-Symbioflor® t.i.d or placebo between 2 and 7 months of age and an observation period until the age of 3 years.

Acronym

PAPS

Study hypothesis

Pro-Symbioflor® is an immunologically active product containing components of a mixture of Escherichia coli (gram negative) and Enterococcus faecalis (gram positive).
Pro-Symbioflor® is claimed to be effective as an immunomodulatory acting drug in the primary prevention of atopic dermatitis and other allergic diseases. To prove this, a trial was designed to test for the Verum - Placebo superiority in the preventive efficacy lowering the risk to develop an atopic disease under a 6 months lasting prophylactic treatment with Pro-Symbioflor® in newborns/ small children aged between 4 weeks and 3 years. In addition its immunomodulatory effects were to be studied.
Null hypothesis H0: The risk of a manifestation of atopic dermatitis (AD) under treatment verum or placebo is not different. Alternative hypothesis H1: The risk of a manifestation of AD under treatment with verum is twice as low as under placebo.

Ethics approval

1. The independent ethics committee (IEC) at Charité approved on the 2nd of March 2002 (ref: 19/2002)
2. Intermediate evaluation of the study (half of cases completed) was carried out and approval to continue granted on the 21st of October 2005
3. Amendment to the protocol approved on the 7th of March 2007

Study design

Prospective randomised placebo controlled double blind parallel group trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Prevention

Patient information sheet

Not available in web format, please use contact details below to request a patient information sheet

Condition

Atopic dermatitis

Intervention

1. Intervention group:
Pro-Symbioflor® (verum): Bacterial lysate manufactured from 1,5 – 4,5 x 10E+07 Enterococcus faecalis (DSM 16440) and 1,5 – 4,5 x 10E+07 Escherichia coli (DSM 17252). 3x5 drops per day for 2 weeks then increased to 3x10 drops per day between 2 and 7 months of age.
2. Control group:
Pro-Symbioflor® (placebo): Culture medium without bacteria. 3x5 drops daily, for 2 weeks increased to 3x10 drops daily between 2 and 7 months of age.

The total duration of follow up will be 3 years.

Intervention type

Other

Phase

Not Specified

Drug names

Primary outcome measures

Incidence of atopic dermatitis during the treatment phase between the 4th and 31st life week under the prophylaxis with verum or placebo.

Secondary outcome measures

1. Incidence of atopic dermatitis after treatment and until end of 3 years
2. Time until the first manifestation of an AD
3. Severity of AD at manifestation of an eczema: SCORing Atopic Dermatitis (SCORAD) Score
4. Frequency and time until the appearance as well as severity of allergic/atopic manifestations in the gastrointestinal tract
5. Frequency and until the appearance as well as severity of an allergic/atopic manifestation in the airways
6. Frequency of a sensitization against food allergens
7. Induction / enhancement of a Th1-immune response
8. Toll-like-receptors
9. Safety pharmacological Investigations before and at the end of the treatment as well as the observation period
10. Adverse events

Overall trial start date

28/05/2002

Overall trial end date

19/09/2010

Reason abandoned

Eligibility

Participant inclusion criteria

1. Healthy male and female newborns aged 4 weeks
2. Regularly developed newborns - body weight: ≥ 2500 g; gestational age > 37+0 weeks
3. No relevant illnesses since the birth (except transient Hyperbilirubinemia)
4. Positive atopic anamnesis with at least one parent (atopic dermatitis, bronchial asthma, allergic rhino-conjunctivitis)
5. Written informed consent by the parents as the legal representatives

Participant type

Patient

Age group

Neonate

Gender

Both

Target number of participants

632

Participant exclusion criteria

1. Diseases that require immunosuppressive therapy (systemic administration of steroids or cyclosporine A)
2. Transfer to an intensive care unit after birth
3. Known immune disturbances or defects (Lymphopenia, Thrombopenia)
4. Concomitant medication or treatment (except for prophylaxis)
5. Inadequate ability or willingness of the parents to communicate or to cooperate
6. Family anamnesis of a congenital deficiency in immune defence

Recruitment start date

28/05/2002

Recruitment end date

19/09/2010

Locations

Countries of recruitment

Germany

Trial participating centre

Department of Pediatric Pneumology and Immunology
Berlin
13353
Germany

Sponsor information

Organisation

SymbioPharm GmbH (Germany)

Sponsor details

Auf den Lüppen 8
Herborn
35745
Germany
kurt.zimmermann@symbio.de

Sponsor type

Industry

Website

http://www.symbiopharm.de

Funders

Funder type

Industry

Funder name

Symbiopharm GmbH (Germany)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2013 results in: http://www.ncbi.nlm.nih.gov/pubmed/23900058

Publication citations

  1. Results

    Penders J, Gerhold K, Stobberingh EE, Thijs C, Zimmermann K, Lau S, Hamelmann E, Establishment of the intestinal microbiota and its role for atopic dermatitis in early childhood., J. Allergy Clin. Immunol., 2013, 132, 3, 601-607.e8, doi: 10.1016/j.jaci.2013.05.043.

Additional files

Editorial Notes