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Trial registered on ANZCTR


Registration number
ACTRN12609000734268
Ethics application status
Approved
Date submitted
19/08/2009
Date registered
25/08/2009
Date last updated
12/06/2019
Date data sharing statement initially provided
12/06/2019
Date results information initially provided
12/06/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
The Melbourne Atopy Cohort Study (MACS): A Randomised controlled trial of a partially hydrolysed whey and a soy formula for the prevention of allergic disease.
Scientific title
In children with a family history of allergic disease does consumption of a partially hydrolysed whey or a soy formula at the cessation or partial cessation of breastfeeding, when compared to conventional cows’ milk formula reduce the incidence of allergic disease
Secondary ID [1] 283672 0
Nil known
Universal Trial Number (UTN)
Trial acronym
MACS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Allergic manifestations
Eczema
Asthma
Allergic rhinitis
Atopy
243548 0
Condition category
Condition code
Inflammatory and Immune System 239852 239852 0 0
Allergies
Diet and Nutrition 239863 239863 0 0
Other diet and nutrition disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Arm 1: Partially hydrolysed whey formula (Nan HA) given as required, at the cessation, or partial cessation of breastfeeding, up to 12 months of age. Administered orally after mixing 4.4g of powdered formula to every 30 ml of warm water.
Arm2: Soy formula (Prosobee) given as required, at the cessation, or partial cessation of breastfeeding, up to 12 months of age. Administered orally after mixing 4.4g of powdered formula to every 30 ml of warm water
Intervention code [1] 241154 0
Prevention
Comparator / control treatment
Conventional cows' milk formula (NAN) given as required, at the cessation, or partial cessation of breastfeeding, up to 12 months of age. Administered orally after mixing 4.3g of powdered formula to every 30 ml of warm water
Control group
Active

Outcomes
Primary outcome [1] 240618 0
Allergic manifestations (eczema, food reactions, urticaria) assessed by telephone interview of parent
Timepoint [1] 240618 0
up to 2 years age. Telephone interviews were undertaken 18 times during the first two years of life (every 4 weeks until 64 weeks, then at 78 and 104 weeks)
Secondary outcome [1] 257255 0
eczema (assessed by telephone interview of parent)
Timepoint [1] 257255 0
up to 2 years age. Telephone interviews were undertaken 18 times during the first two years of life (every 4 weeks until 64 weeks, then at 78 and 104 weeks)
Secondary outcome [2] 257256 0
atopy (positive skin prick test)
Timepoint [2] 257256 0
6, 12, and 24 months of age, and 12, 18 and 25 years
Secondary outcome [3] 257257 0
eczema assessed by questionnaire designed specifically for this study at all time points, and using the validated International Study of Asthma and Allergies in Childhood questions at the 12, 18 and 25 year follow-up.
Timepoint [3] 257257 0
5-7, 12, 18 and 25 years of age. A questionnaire was conducted when the child was six, seven, 12, 18 and 25 years of age, At 12 years and younger, questions were asked of parents. At 18 and 25 years, participants were asked directly. The quesionnaire asked if the participant had had any episodesof eczema in the previous 12 months.
Secondary outcome [4] 257258 0
asthma assessed by questionnaire designed specifically for this study at all time points, and using the validated International Study of Asthma and Allergies in Childhood questions at the 12, 18 and 25 year follow-up.
Timepoint [4] 257258 0
5-7, 12, 18 and 25 years of age. A questionnaire was conducted when the child was six, seven, 12, 18 and 25 years of age, At 12 years and younger, questions were asked of parents. At 18 and 25 years, participants were asked directly. The quesionnaire asked if the participant had had any episodesof asthma in the previous 12 months.
Secondary outcome [5] 257259 0
allergic rhinitis assessed by questionnaire designed specifically for this study at all time points and using the validated International Study of Asthma and Allergies in Childhood questions at the 12, 18 and 25 year follow-up.
Timepoint [5] 257259 0
5-7, 12, 18 and 25 years of age. A questionnaire was conducted when the child was six, seven, 12, 18 and 25 years of age, At 12 years and younger, questions were asked of parents. At 18 and 15 years, participants were asked directly. The quesionnaire asked if the participant had had any episodesof asthma in the previous 12 months.
Secondary outcome [6] 349315 0
Lung function as assessed by spirometry
Timepoint [6] 349315 0
12, 18 and 25 years

Eligibility
Key inclusion criteria
Family history of allergic disease (asthma, eczema, allergic rhinitis or severe food allergy)
Minimum age
0 Years
Maximum age
0 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Nil

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Mother-baby pairs were allocated to the next sequential number on the allocation list as they were enrolled in the study, and were assigned to the formula code allocated to that number. The tins of formula were labeled at an independent location with a code number. Neither the study staff or particpants knew which formula was assigned to each tin code number.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation by using a randomisation table created by a computer program
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 237520 0
Commercial sector/Industry
Name [1] 237520 0
Nestec Ltd,
Address [1] 237520 0
Avenue Nestle 55 CH - 180-0 Vevey
Country [1] 237520 0
Switzerland
Funding source category [2] 237521 0
Government body
Name [2] 237521 0
National Health and Medical Research Council (NHMRC)
Address [2] 237521 0
GPO Box 1421
Canberra ACT 2601
Country [2] 237521 0
Australia
Funding source category [3] 237522 0
Charities/Societies/Foundations
Name [3] 237522 0
Victorian Asthma Foundation
Address [3] 237522 0
491-495 King Street, West Melbourne
Victoria, 3003
Country [3] 237522 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Nestec Ltd,
Address
Avenue Nestle 55 CH - 180-0 Vevey
Country
Switzerland
Secondary sponsor category [1] 236998 0
None
Name [1] 236998 0
Address [1] 236998 0
Country [1] 236998 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 243653 0
Mercy Hospital Human Research Ethics Committee
Ethics committee address [1] 243653 0
Mercy Hospital for Women 163 Studley Road HEIDELBERG VIC 3084
Ethics committee country [1] 243653 0
Australia
Date submitted for ethics approval [1] 243653 0
Approval date [1] 243653 0
19/01/1989
Ethics approval number [1] 243653 0

Summary
Brief summary
Despite a lack of clear evidence, partially hydrolysed whey formula has been recommended at the cessation of exclusive breast-feeding in infants at high risk of developing allergic disease. It is thought that partially hydrolysed whey formula may promote oral tolerance and prevent allergic diseases. Similarly, soy formula has previously been recommended for allergy prevention. The primary aim of this study was to determine if the use of a partially hydrolysed formula, or a soy formula, at the cessation, or partial cessation of breastfeeding, reduced the incidence of allergic manifestations (eczema, urticaria and food reactions), in high-risk infants when compared with a conventional cows’ milk formula.
Trial website
Trial related presentations / publications
1. Tang MLK, Kemp AS, Thorburn J, Hill DJ. Reduced IFNy secretion in neonates and subsequent atopy. Lancet 1994;344:983-5.
2. Hill DJ, Hosking CS, Yu Zhie C, Leung R, Baratwidjaja K, Iikura Y, et al. The frequency of food allergy in Australia and Asia. Environ Toxicol and Pharma 1997;4:101-10.
3. Hill DJ, Sporik RS, Thorburn J, Hosking CS. The Association of Atopic Dermatitis in Infancy with Immunoglobulin E Food Sensitization. J Pediatr 2000;137:475-9.
4. Stoney RM, Woods RK, Hosking CS, Hill DJ, Abramson MJ, Thien FC. Maternal breast milk long-chain n-3 fatty acids are associated with increased risk of atopy in breastfed infants. Clin Exp Allergy 2004;34:194-200.
5. Hill DJ, Hosking CS. Food Allergy and Atopic Dermatitis in Infancy: an epidemiological study. Pediatr Allergy Immunol 2004;15:421-7.
6. Lowe AJ, Carlin JB, Bennett CM, Abramson MJ, Hosking CS, Hill DJ, et al. Atopic disease and breastfeeding - cause or consequence? J Allergy Clin Immunol 2006;117:682-7.
7. Lowe AJ, Abramson MJ, Hosking CS, Carlin JB, Bennett CM, Dharmage SC, Hill DJ. The temporal sequence of allergic sensitization and onset of infantile eczema. Clin Exp Allergy 2007;37:536-42.
8. A.J. Lowe, C.S. Hosking, C.M. Bennett, J.B. Carlin, M.J. Abramson, D.J. Hill, S.C. Dharmage Skin prick test can identify eczematous infants at risk of asthma and allergic rhinitis. 2007 Clin Exp Allergy
9. Hosking CS, Hill DJ, Thorburn J. Dharmage S. Does infection enhance or suppress the development of the atopic status? - a study of rhinitis in atopy-prone infants. Pediatric Asthma Allergy and Immunology 2007; 20(4): 223-228
10. Koplin J, Dharmage SC, Gurrin L, Osborne N, Tang ML, Lowe AJ, Hosking C, Hill D, Allen KJ. Soy consumption is not a risk factor for peanut sensitization. J Allergy Clin Immunol. 2008; 121:1455-9.
11. Lowe AJ, Carlin JB, Bennett CM, Hosking CS, Abramson MJ, Hill DJ, Dharmage SC. Do boys do the atopic march while girls dawdle? J Allergy Clin Immunol. 2008;121: 1190-5.
12. Lowe AJ, Thien FCK, Stoney RM, Bennett CM, Hosking CS, Hill DJ, Carlin JB, Abramson MJ, Dharmage SC. Associations between fatty-acids in colostrum and breast-milk and risk of allergic disease. Clinical and Experimental Allergy. 2008; 38:1745-1751.
13. Lodge CJ, Lowe AJ, Gurrin LC, Matheson MC, Balloch A, Axelrad C, et al. Pets at birth do not increase allergic disease in at-risk children. Clin Exp Allergy 2012; 42:1377-85.
14. Lowe AJ, Hosking CS, Bennett CM, Allen KJ, Axelrad C, Carlin JB, et al. Effect of a partially hydrolyzed whey infant formula at weaning on risk of allergic disease in high-risk children: A randomized controlled trial. J Allergy Clin Immunol 2011; 128:360-5.
15. Lodge CJ, Lowe AJ, Gurrin LC, Hill DJ, Hosking CS, Khalafzai RU, et al. House dust mite sensitization in toddlers predicts current wheeze at age 12 years. J Allergy Clin Immunol 2011; 128:782-8 e9.
16. Seach KA, Dharmage SC, Lowe AJ, Dixon JB. Delayed introduction of solid feeding reduces child overweight and obesity at 10 years. Int J Obes (Lond) 2010; 34:1475-9.
17. Lowe AJ, Carlin JB, Bennett CM, Hosking CS, Allen KJ, Robertson CF, et al. Paracetamol use in early life and asthma: prospective birth cohort study. BMJ 2010; 341:c4616.
18. Lodge CJ, Lowe AJ, Gurrin LC, Matheson MC, Balloch A, Axelrad C, Hill DJ, Hosking CS, Rodrigues S, Svanes C, Abramson MJ, Allen KJ, Dharmage SC: Pets at birth do not increase allergic disease in at-risk children. Clinical & Experimental Allergy, 2012, 42: 1377-1385.
19. Erbas B, Lowe A, Lodge C, Matheson M, Hosking C, Hill D, Vicendese D, Allen K, Abramson M, Dharmage S. Persistent pollen exposure during infancy is associated with increased risk of subsequent childhood asthma and hay fever. Clin Exp Allergy, 2013, 43(3): 337-43.
20. Lodge C, Zaloumis S, Lowe AL, Gurrin LC, Matheson MC, Axelrad C, Bennett CM, Hill D, Hosking C, Svanes C, Abramson MJ, Allen KJ, Dharmage SC. Early-life risk factors for childhood Wheeze phenotypes in a high-risk birth cohort. Journal of Paediatrics. 2014; 164: 289-294.
21. Lodge C, Lowe AL, Allen KJ, Zaloumis S, , Gurrin LC, Matheson MC, Axelrad C, Welsh L, Bennett CM, Hopper J, Thomas PS, Hill D, Hosking C, Svanes C, Abramson MJ, Dharmage SC. Some early childhood wheeze phenotypes are associated with reduced lung growth in adolescence. American Journal of Respiratory and Critical Care Medicine. 2014; 189: 1351-58.
22. Alduraywish S, Lodge C, Vicendese D, Lowe A, Erbas B, Matheson M, Hopper J, Hill D, Axelrad C, Abramson M, Dharmage S, Allen K. Sensitization to milk, egg and peanut from birth to 18 years: a longitudinal study of a cohort at risk of allergic disease. Pediatric Allergy and Immunology. 2016; 27(1) 83-91.
23. Bowatte G, Lodge C, Lowe A, Erbas B, Dennekamp M, Marks G, Perret J, Hui J, Wjst M, Gurrin L, Allen K, Abramson M, Matheson M, Dharmage S. Do Variant s in GSTs Modify the Association between Traffic Air Pollution and Asthma in Adolescence? International Journal of Molecular Sciences. 2016; 17, 485.
24. Waidyatillake NT, Simpson JA, Allen KJ, Lodge CJ, Dharmage SC, Abramson MJ, De Livera AM, Matheson MC, Erbas B, Hill DJ, Lowe AJ. The Effect of Breastfeeding on Lung Function at 12 and 18 Years – a prospective cohort study. European Respiratory Journal. 2016;48(1):125-132.
25. Fuertes E, Markevych I, Bowatte G, Gruzieva O, Gehring U, Becker A, Berdel D, von Berg A, Bergström A, Brauer M, Brunekreef B, Brüske I, Carlsten C, Chan-Yeung M, Dharmage SC, Hoffmann B, Klümper C, Koppelman GH, Kozyrskyj A, Korek M, Kull I, Lodge C, Lowe A, MacIntyre E, Pershagen G, Standl M, Sugiri D, Wijga A, MACS, Heinrich J. Residential greenness is differentially associated with childhood allergic rhinitis and aeroallergen sensitization in seven birth cohorts. Allergy; 2016; 10: 1461-71.
26. Alduraywish SA, Standl M, Lodge CJ, Abramson MJ, Allen KJ, Erbas B, v. Berg A, Heinrich J, Lowe AJ, Dharmage SD. Is there a march from early food sensitization to later childhood allergic airway disease? Results from two prospective birth cohort studies, Pediatric Allergy and Immunology. 2017; 28: 30-7.
27. Lowe AJ, Lodge CJ, Allen KJ, Abramson MJ, Matheson MC, Thomas PS, Barton CA, Bennett C, Erbas B, Svanes C, Wjst M, Real FG, Perret J, Russell M, Southey M, Hopper J, Gurrin L, Axelrad C, Hill D, Dharmage S . The Melbourne Atopy Cohort study (MACS) - Cohort profile. International Journal of Epidemiology. 2017; 46(1): 25-26.
28. Waidyatillake NT, Stoney R, Thien F, Lodge CJ, Simpson JA, Allen KJ, Abramson MJ, Erbas B, Svanes C, Dharmage SC, Lowe AJ. Breast milk poly unsaturated fatty acids: associations with adolescent allergic disease and lung function. Allergy. 2017; 72: 1193-1201.
29. Dai X, Dharmage SC, Lowe AJ, Allen KJ, Thomas PS, Perret J, Waidyatillake N, Matheson MC, Svanes C, Welsh L, Abramson MJ, Lodge CJ. Early smoke exposure is associated with asthma and lung function deficits in adolescents. J Asthma. 2017; 54(6): 662-9.
30. Lowe AJ, Angelica B, Su J, Lodge CJ, Hill DJ, Erbas B, Bennett CM, Gurrin LC, Axelrad C, Abramson MJ, Allen KJ, Dharmage SC. Age at onset and persistence of eczema are related to subsequent risk of asthma and hay fever from birth to 18 years of age. Pediatr Allergy Immunol. 2017; 28: 384-390.
31. Ashley SE, Tan HTT, Vuillermin P, Dharmage SC, Tang MLK, Koplin J, Gurrin LC, Lowe AJ, Lodge C, Ponsonby AL, Molloy J, Martin P, Matheson MC, Saffery R, Allen KJ, Ellis JA, Martino D and the HealthNuts team. The skin barrier function gene SPINK5 is associated with challenge proven IgE-mediated food allergy in infants. Allergy. 2017: 72; 1356-64.
32. Peters RL, Koplin JJ, Allen KJ, Lowe AJ, Lodge C, Tang MLK, Wake M, Ponsonby AL, Erbas B, Abramson MJ, Hill D, Gurrin LC, Dharmage SC. The prevalence of food sensitization appears not to have changed between two Melbourne cohorts of high-risk infants recruited 15 years apart. Clinical Immunology – In practice. 2018: 6;440-448.e2.
33. Susanto NH, Malby Schoos AN, Standl M, Lowe AJ, Dharmage SC, Svanes C, Salim A, von Berg A, Lehmann I, Rasmussen MA, Werchan M, Bergmann KA, Lodge C, Abramson MJ, Heinrich J, Bisgaard H, Erbas B Environmental grass pollen levels in utero and at birth and Cord Blood IgE: Analysis of three birth cohorts. Environmental International. Accepted 26/6/2018.
Public notes

Contacts
Principal investigator
Name 30071 0
Prof Shyamali Dharmage
Address 30071 0
Centre for Epidemiology and Biostatistics
Melbourne School of Population and Global Health
L3, 207 Bouverie Street
University of Melbourne VIC 3010
Country 30071 0
Australia
Phone 30071 0
+61 3 83440737
Fax 30071 0
Email 30071 0
s.dharmage@unimelb.edu.au
Contact person for public queries
Name 13318 0
Dr Dr David Hill
Address 13318 0
Senior Consultant Allergist
Murdoch Children's Research Institute
The Royal Children’s Hospital
Flemington Road Parkville Victoria 3052
Country 13318 0
Australia
Phone 13318 0
+61 3 8344 0878
Fax 13318 0
Email 13318 0
davidjlhill@bigpond.com
Contact person for scientific queries
Name 4246 0
Dr Dr David Hill
Address 4246 0
Senior Consultant Allergist
Murdoch Children's Research Institute
The Royal Children’s Hospital
Flemington Road Parkville Victoria 3052
Country 4246 0
Australia
Phone 4246 0
+61 3 8344 0878
Fax 4246 0
Email 4246 0
davidjlhill@bigpond.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Consent for release of IPD has not been obtained
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
Yes
Journal publication details
Publication date and citation/details [1] 2312 0
Lowe AJ, Hosking CS, Bennett CM, Allen KJ, Axelrad C, Carlin JB, Abramson MJ, Dharmage SC, Hill DJ. Effect of a partially hydrolyzed whey infant formula at weaning on risk of allergic disease in high-risk children: A randomized controlled trial. J Allergy Clin Immunol, 2011, 128: 360-5.
Attachments [1] 2312 0
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary