Milk Against Respiratory Tract Infections and Asthma

Organizational Data

DRKS-ID:
DRKS00014781
Recruitment Status:
Recruiting complete, study continuing
Date of registration in DRKS:
2018-10-01
Last update in DRKS:
2023-11-29
Registration type:
Prospective

Acronym/abbreviation of the study

MARTHA

URL of the study

http://www.martha-studie.de

Brief summary in lay language

Frequency of asthma and allergic diseases, e.g. hayfever or atopic eczema, have increased in Germany throughout the past years. Several studies identified protective factors on farms that prevent from asthma and allergies, e.g. raw milk. With the MARTHA study we aim to test if a mildly pasteurized milk is able to prevent development of respiratory infections, asthma and allergies in children. Therefore, we compare the mildly pasteurized milk with regularly treated milk. All children who are at least 6 months old can participate. Participants will be randomized and allocated to a study arm by chance. One group receives the mildly pasteurized milk, the other group the regularly treated milk. All study participants consume one bottle (glass, mug) of their test milk daily until the age of 3 years.

Brief summary in scientific language

Studies examining farm children and farm milk consumption have consistently shown inverse associations between consumption of farm milk and asthma, allergies and respiratory infections leading to the hypothesis that unprocessed cow's milk protects from these conditions. The MARTHA study tests this hypothesis in a randomized controlled trial in infants. Between 6 and 12 months infants start after weaning with drinking daily 200ml milk. From the age of 10 months on infants receive twice daily 150ml milk. One group receives minimally processed milk. This minimally processed milk has been processed only to prevent transmission of germs and diseases according to legal requirements for pasteurized milk. For comparison the other group receives semi-skimmed, ultra-heat treated (UHT) milk as it is used in follow-on formula. The milks are indistinguishable by appearance and packaging. Neither the investigators nor the family will be informed to which study arm the infant is allocated until the end of the study. Administration of the milk continues until the age of 3 years. The milk-intervention period is followed by an observational period of 2 years, until the age of 5 years. During the 2½ years of intervention period parents will answer a weekly web-based diary with questions on how well the milk was tolerated, whether respiratory tract infections or other relevant medical conditions occurred, and on consumption of supplemental solid foods. Every quarter additional questions regarding living environment including day care visits and animal exposure will be asked. Children will participate at a total of 3 clinical visits. At 6 months of age, infants undergo a clinical examination (capillary blood sampling (300µl) and other samples including nasal and buccal swabs) and are enrolled according to inclusion and exclusion criteria as well as randomized to treatment arms. The second visit is performed during intervention and the third marks the end of the intervention phase at age 3 years. During these visits children undergo clinical examination (biosamples will be collected again) and the secondary outcomes such as atopic eczema will be assessed. The primary outcome atopic sensitization will be assessed at the third and final visit.

Health condition or problem studied

ICD10:
J45 - Asthma
ICD10:
J06 - Acute upper respiratory infections of multiple and unspecified sites
ICD10:
T78.4 - Allergy, unspecified
Healthy volunteers:
Yes

Interventions, Observational Groups

Arm 1:
Test milk; mildly pasteurized, not further processed cow's milk; from 6 to 9 months: daily 200ml milk; from 10 to 35 months: twice daily 150ml milk
Arm 2:
Regularly processed cow's milk; from 6 to 9 months: daily 200ml milk; from 10 to 35 months: twice daily 150ml milk

Endpoints

Primary outcome:
Atopic sensitization at age 3 years
Secondary outcome:
Physician diagnosis of asthma until age 5; Rhinitis irrespective of cough and wheeze until age 3 years; Respiratory tract infections without wheeze until age 3 years; Otitis media until age 3 years; Atopic eczema at age 3 years; Levels of high-sensitivity C-reactive protein in serum at age 3 years

Study Design

Purpose:
Prevention
Allocation:
Randomized controlled study
Control:
  • Placebo
Phase:
N/A
Study type:
Interventional
Mechanism of allocation concealment:
No Entry
Blinding:
Yes
Assignment:
Parallel
Sequence generation:
No Entry
Who is blinded:
  • Assessor
  • Data analyst
  • Investigator/therapist
  • Patient/subject

Recruitment

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

Recruitment Locations

Recruitment countries:
  • Germany
Number of study centers:
Multicenter study
Recruitment location(s):
  • University medical center Dr. von Haunersches Kinderspital München
  • University medical center Krankenhaus Barmherzige Brüder Regensburg - Klinik St. Hedwig Regensburg

Recruitment period and number of participants

Planned study start date:
2018-10-01
Actual study start date:
2018-11-07
Planned study completion date:
2025-12-31
Actual Study Completion Date:
No Entry
Target Sample Size:
960
Final Sample Size:
260

Inclusion Criteria

Sex:
All
Minimum Age:
6 Months
Maximum Age:
12 Months
Additional Inclusion Criteria:
Healthy, term-born (35 gestational weeks) infants of both sexes; Age 6 to 12 months at randomization; Caregivers with the ability to follow study instructions and likely to attend and complete all required visits; Caregivers have a mobile phone or a personal computer and are likely to keep a web-based diary regularly; Written informed consent of the parents or guardians

Exclusion Criteria

Suspected or confirmed cow’s milk allergy, milk intolerance, lactose intolerance, suspected immunodeficiency, cystic fibrosis, failure to thrive; Simultaneous participation in another intervention study; Maternal age below 18 years; Uncertainty of the study physician about prospective adherence to study protocol, e.g. known or persistent abuse of medication, drugs or alcohol in caregivers; A sibling already enrolled

Addresses

Primary Sponsor

Address:
Klinikum der Universität München - Dr. von Haunersches Kinderspital
Prof. Dr. Dr.h.c. Erika von Mutius
Lindwurmstraße 4
80337 München
Germany
Telephone:
+49 (0)89 4400 57897
Fax:
+49 (0)89 4400 54452
Contact per E-Mail:
Contact per E-Mail
URL:
http://www.klinikum.uni-muenchen.de/Kinderklinik-und-Kinderpoliklinik-im-Dr-von-Haunerschen-Kinderspital/de/index.html
Investigator Sponsored/Initiated Trial (IST/IIT):
Yes

Contact for Scientific Queries

Address:
Klinikum der Universität München - Dr. von Haunersches Kinderspital
Prof.Dr. Dr.h.c. Erika von Mutius
Lindwurmstraße 4
80337 München
Germany
Telephone:
+49 (0)89 4400 57897
Fax:
+49 (0)89 4400 54452
Contact per E-Mail:
Contact per E-Mail
URL:
http://www.klinikum.uni-muenchen.de/Kinderklinik-und-Kinderpoliklinik-im-Dr-von-Haunerschen-Kinderspital/de/index.html

Contact for Public Queries

Address:
Klinikum der Universität München - Dr. von Haunersches Kinderspital - Studiensekretariat MARTHA Studie
Maistraße 11 (Frauenklinik)
80337 München
Germany
Telephone:
089 4400 57930
Fax:
089 4400 54452
Contact per E-Mail:
Contact per E-Mail
URL:
http://www.klinikum.uni-muenchen.de/Kinderklinik-und-Kinderpoliklinik-im-Dr-von-Haunerschen-Kinderspital/de/index.html

Principal Investigator

Address:
Klinikum der Universität München - Dr. von Haunersches Kinderspital
Prof.Dr. Dr.h.c. Erika von Mutius
Lindwurmstraße 4
80337 München
Germany
Telephone:
+49 (0)89 4400 57897
Fax:
+49 (0)89 4400 54452
Contact per E-Mail:
Contact per E-Mail
URL:
http://www.klinikum.uni-muenchen.de/Kinderklinik-und-Kinderpoliklinik-im-Dr-von-Haunerschen-Kinderspital/de/index.html

Sources of Monetary or Material Support

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

Address:
FrieslandCampina
Stationsplein 4
3818 LE Amersfoort
Netherlands
Telephone:
No Entry
Fax:
+31 (0)33 7133333
Contact per E-Mail:
Contact per E-Mail
URL:
No Entry

Private sponsorship (foundations, study societies, etc.)

Address:
Longfonds Stichting
Stationsplein127
3818 LE Amersfoort
Netherlands
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 Med. Fakultät der LMU
Pettenkoferstraße 8
80336 München
Germany
Telephone:
+49-89-440055191
Fax:
+49-89-440055192
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:
2018-05-30
Ethics committee number:
18-405
Vote of the Ethics Committee:
Approved
Date of the vote:
2018-08-06

Further identification numbers

Other primary registry ID:
No Entry
EudraCT Number:
No Entry
UTN (Universal Trial Number):
U1111-1216-7580
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:
Statistical Analysis Plan (a signed version is stored locally)
Background literature:
No Entry
Related DRKS studies:
No Entry

Publication of study results

Planned publication:
No Entry
Publikationen/Studienergebnisse:
No Entry
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