Clinical trial NCT02911194: a2 Milk for Autism and Attention-deficit Hyperactivity Disorder (ADHD)
Official title: A1 Beta Casein Free Milk (a2 Milk) for Autism and Attention-deficit Hyperactivity Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Autism
Attention Deficit Hyperactivity Disorder
Autism Spectrum Disorder
Lead sponsor: Northumbria University
Sponsor class: OTHER
Collaborators: name: ESPA Research
name: a2 Milk Company Ltd.
First posted: 2016-09-22
Enrollment: 40
Sex: MALE
Minimum age (years): 5
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Under double-blind, placebo-controlled, cross-over conditions, the short-term effects of use of A1 beta casein free milk (a2 milk) and milk containing A1 beta casein will be compared in a sample of pre-pubescent boys diagnosed with an autism spectrum disorder (ASD) with concurrent features of attention-deficit hyperactivity disorder (ADHD).

Detailed description: Previous preliminary research studies have suggested that a diet devoid of milk and dairy products might be useful for some people on the autism spectrum in reducing certain types of behaviours or other symptoms that can affect quality of life. Aggravation of some of the symptoms of autism has been suggested to be linked to some of the constituents of milk, in particular a natural breakdown product of the milk protein called beta-casomorphin 1-7 (BC 1-7 or BCM-7) found in the majority of mammalian dairy products. A dairy-free diet (casein-free diet) can however be a difficult diet to follow and may increase the risk that certain nutrients are missing from the diet.

Anecdotal evidence suggests that different types of milk from different breeds of cattle (cows) may not carry the same biological effects for some on the autism spectrum. Milk typically found in supermarkets naturally contains BC1-7 as a function of the type of cows producing the milk and the protein it contains (A1 variant of the beta casein protein).

The investigators are aiming to test whether a particular type of milk (A1 beta casein free milk also called a2 Milk™) might be able to replace a casein-free diet for children on the autism spectrum also presenting with attention-deficit hyperactivity disorder (ADHD) type symptoms. The investigators will be looking at the potential effects of A1 beta casein free milk on behaviour and various biological processes going on in the body. The source of A1 beta casein free milk will be commercially available a2 Milk™ branded milk that is directly comparable to regular supermarket bought milk with the exception of the beta casein component and is already available to buy.

In this double-blind, randomised, placebo-controlled trial, the effects of milk free of A1 beta casein (a branded milk called a2 milk™) and milk containing A1 beta casein will be compared in a sample of pre-pubescent children diagnosed with an autism spectrum disorder with concurrent features of attention-deficit hyperactivity disorder (ADHD). Forty children based in North East England will be initially recruited; all possessing communicative speech and language. A baseline assessment will be conducted to include behavioural, psychometric and health-related parameters. Following random allocation, participants will be assigned to group A or group B and given A1 milk or a2 Milk™ initially for a period of 4 weeks. At this point, baseline assessment measures will be repeated. Milk types will be crossed for groups for a further 4 weeks. At study endpoint, baseline assessment measures will be repeated again. Data derived from the study will be analysed and outcomes reported in peer-review format. During the course of the study, all other forms of dairy product consumption (cheese, yogurts, etc) will be excluded from the diet of all participants irrespective of their treatment allocation.

Data from supervised baseline, midpoint and endpoint psychometric and behavioural assessments will be made and stored via a secure survey website accessed via tablets supplied to all participants.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of autism spectrum disorder (autism, Asperger syndrome, Autism Spectrum Disorder)
* Diagnosis or fulfilling the diagnostic criteria for / presenting with the symptoms of attention-deficit hyperactivity disorder (ADHD)
* Regular milk drinker
* Functional use of spoken language (for ability to self-report)
* Access to internet connection (WiFi)

Exclusion Criteria:

* Undergoing current medical treatment (and an inpatient at a state hospital)
* Current or past 3 month use of a gluten- and/or casein-free diet
* Co-morbid diagnoses of Fragile-X syndrome, epilepsy or tuberous sclerosis
* Indications or diagnosis of cows milk protein allergy (IgE)

Primary outcomes:
measure: Change in Childhood Autism Rating Scale (CARS2-HF) Value during intervention
timeFrame: Baseline to Week 4 to Week 8
measure: Change in Conners' Rating Scale - Revised (L) value during intervention.
timeFrame: Baseline to Week 4 to Week 8
Secondary outcomes:
measure: Amino acid analysis of urine samples by mass spectroscopy.
timeFrame: Baseline to Week 4 to Week 8
measure: Metabolomic analysis of blood spot samples by mass spectroscopy.
timeFrame: Baseline to Week 4 to Week 8
measure: Changes to the gut microbiome profile.
timeFrame: Baseline to Week 4 to Week 8
measure: Changes to stool appearance measured using the Bristol Stool Chart.
timeFrame: Baseline to Week 4 to Week 8
Other outcomes:
Locations:
city: Sunderland
country: United Kingdom
facility: ESPA Research
state: Tyne And Wear
Study officials:
affiliation: Northumbria University
name: John K Lodge, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Whiteley P. Nutritional management of (some) autism: a case for gluten- and casein-free diets? Proc Nutr Soc. 2015 Aug;74(3):202-7. doi: 10.1017/S0029665114001475. Epub 2014 Oct 14.
citation: Pedersen L, Parlar S, Kvist K, Whiteley P, Shattock P. Data mining the ScanBrit study of a gluten- and casein-free dietary intervention for children with autism spectrum disorders: behavioural and psychometric measures of dietary response. Nutr Neurosci. 2014 Sep;17(5):207-13. doi: 10.1179/1476830513Y.0000000082. Epub 2013 Nov 26.
citation: Whiteley P, Shattock P, Knivsberg AM, Seim A, Reichelt KL, Todd L, Carr K, Hooper M. Gluten- and casein-free dietary intervention for autism spectrum conditions. Front Hum Neurosci. 2013 Jan 4;6:344. doi: 10.3389/fnhum.2012.00344. eCollection 2012.
citation: Whiteley P, Haracopos D, Knivsberg AM, Reichelt KL, Parlar S, Jacobsen J, Seim A, Pedersen L, Schondel M, Shattock P. The ScanBrit randomised, controlled, single-blind study of a gluten- and casein-free dietary intervention for children with autism spectrum disorders. Nutr Neurosci. 2010 Apr;13(2):87-100. doi: 10.1179/147683010X12611460763922.
citation: Jianqin S, Leiming X, Lu X, Yelland GW, Ni J, Clarke AJ. Effects of milk containing only A2 beta casein versus milk containing both A1 and A2 beta casein proteins on gastrointestinal physiology, symptoms of discomfort, and cognitive behavior of people with self-reported intolerance to traditional cows' milk. Nutr J. 2016 Apr 2;15:35. doi: 10.1186/s12937-016-0147-z.
citation: Ho S, Woodford K, Kukuljan S, Pal S. Comparative effects of A1 versus A2 beta-casein on gastrointestinal measures: a blinded randomised cross-over pilot study. Eur J Clin Nutr. 2014 Sep;68(9):994-1000. doi: 10.1038/ejcn.2014.127. Epub 2014 Jul 2.
citation: Trivedi MS, Shah JS, Al-Mughairy S, Hodgson NW, Simms B, Trooskens GA, Van Criekinge W, Deth RC. Food-derived opioid peptides inhibit cysteine uptake with redox and epigenetic consequences. J Nutr Biochem. 2014 Oct;25(10):1011-8. doi: 10.1016/j.jnutbio.2014.05.004. Epub 2014 Jun 6.