Plain English Summary
Not provided at time of registration
Trial website
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 measure
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 (if study stopped)
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
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
Basic results (scientific)
Publication list
2013 results in: http://www.ncbi.nlm.nih.gov/pubmed/23900058
Publication citations
-
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.