AutismA2MTNCT02911194
a2 Milk for Autism and Attention-deficit Hyperactivity Disorder (ADHD)
A study testing a2 milk and a1 containing milk in people with Autism and Attention Deficit Hyperactivity Disorder, run by Northumbria University at 1 site in United Kingdom.
Trial 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… Read more about this study
- Who is it for?
- Ages 5 to 10 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Autism, Attention Deficit Hyperactivity Disorder, Autism Spectrum Disorder
- What is being tested?
- a2 milk and a1 containing milk
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Sep 2016to Sep 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 10 years
- Men only
- Healthy volunteers accepted
- Child
Who may be able to join
- 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)
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A1 Beta Casein Free Milk (a2 Milk) for Autism and Attention-deficit Hyperactivity Disorder
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).
Read the 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.
- Being tested
- a2 milk, a1 containing milk
- Medical subject headings
- Autistic Disorder, Attention Deficit Disorder with Hyperactivity, Autism Spectrum Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
a2 milkDietary supplement
replace all milk with a2 milk
a1 containing milkDietary supplement
use a1 containing milk
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | a2 milk intervention period Receives: Dietary Supplement: a2 milk |
| Control | Placebo comparator | a1 containing milk (normal) intervention period Receives: Dietary Supplement: a1 containing milk |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Childhood Autism Rating Scale (CARS2-HF) Value during intervention
Difference in CARS raw scores and severity group between baseline and 4 weeks and 8 weeks.
Measured: Baseline to Week 4 to Week 8
Change in Conners' Rating Scale - Revised (L) value during intervention.
Difference in Conners' raw scores and totalled scores between baseline and 4 weeks and 8 weeks
Measured: Baseline to Week 4 to Week 8
Secondary outcomes (4)
Amino acid analysis of urine samples by mass spectroscopy.
Analysis of urine samples via non-targeted and targeted liquid chromatography mass spectrometry analysis. The targeted compounds to be measured include urinary metabolites of intestinal bacterial species (specifically related to the aromatic amino acids, tryptophan, tyrosine and phenylalanine) and urinary concentrations of compounds related to the methionine cycle (including methionine, homocysteine, cystathione and cysteine).
Measured: Baseline to Week 4 to Week 8
Metabolomic analysis of blood spot samples by mass spectroscopy.
Where blood spot samples are/can be provided by participants, non-targeted and targeted liquid chromatography mass spectrometry analysis will be undertaken. The targeted compounds to be measured include various amino acids including the aromatic amino acids and the branched chain amino acids. Blood spot concentrations of compounds related to the methionine cycle (including methionine, homocysteine, cystathione and cysteine) will also be examined.
Measured: Baseline to Week 4 to Week 8
Changes to the gut microbiome profile.
Gene sequencing of stool samples to characterise the gut microbiome measured by operational taxonomic units (OTUs) of individual bacterial species.
Measured: Baseline to Week 4 to Week 8
Changes to stool appearance measured using the Bristol Stool Chart.
At time of stool sample collection, the presentation of the stool will be recorded using the Bristol Stool Chart.
Measured: Baseline to Week 4 to Week 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2016 (estimated)
- Study startSep 2016
- Primary completionSep 2018
- Study completionSep 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for AutismStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northumbria University
- Sponsor type
- University, hospital or other
- Collaborators
- ESPA Research, a2 Milk Company Ltd.
- Responsible party
- Principal investigator, John Lodge, Northumbria University
- Investigators
- John K Lodge, PhD, Principal investigator, Northumbria University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02911194
- Sponsor's protocol ID
- SUB017_Lodge_031115
- Acronym
- A2MT
- Status last verified
- Sep 2018
- First submitted
- 22 Jul 2016
- Last updated
- 5 Sep 2018
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: Group data will be available upon request
Publications
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.
PubMed 25311313Pedersen 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.
PubMed 24075141Whiteley 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.
PubMed 23316152Whiteley 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.
PubMed 20406576Jianqin 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.
PubMed 27039383Ho 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.
PubMed 24986816Trivedi 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.
PubMed 25018147
Study at a glance
From the registry record, last updated by the sponsor on 5 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A1 Beta Casein Free Milk (a2 Milk) for Autism and Attention-deficit Hyperactivity Disorder
- ClinicalTrials.gov ID
- NCT02911194
- Acronym / sponsor ID
- A2MT / SUB017_Lodge_031115
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Northumbria UniversityUniversity, hospital or other
- Collaborators
- ESPA Research, a2 Milk Company Ltd.
- Study start
- Sep 2016
- Primary completion
- Sep 2018 (actual)
- Study completion
- Sep 2018 (actual)
- First posted
- 22 Sep 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Dietary Supplement: a2 milka2 milk intervention period |
| Control | Placebo comparator | Dietary Supplement: a1 containing milka1 containing milk (normal) intervention period |
Who may qualify
- Ages
- 5 to 10 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- 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)
Key exclusion criteria (4 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| a2 milkreplace all milk with a2 milk | Dietary supplement | Treatment |
| a1 containing milkuse a1 containing milk | Dietary supplement | Control |
Primary outcome
Change in Childhood Autism Rating Scale (CARS2-HF) Value during intervention
Time frame: Baseline to Week 4 to Week 8
Difference in CARS raw scores and severity group between baseline and 4 weeks and 8 weeks.
Change in Conners' Rating Scale - Revised (L) value during intervention.
Time frame: Baseline to Week 4 to Week 8
Difference in Conners' raw scores and totalled scores between baseline and 4 weeks and 8 weeks
4 secondary outcomes
Amino acid analysis of urine samples by mass spectroscopy.
Time frame: Baseline to Week 4 to Week 8
Metabolomic analysis of blood spot samples by mass spectroscopy.
Time frame: Baseline to Week 4 to Week 8
Changes to the gut microbiome profile.
Time frame: Baseline to Week 4 to Week 8
Changes to stool appearance measured using the Bristol Stool Chart.
Time frame: Baseline to Week 4 to Week 8
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Sep 2018.
- Background: PubMed 25311313Whiteley 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.
- Background: PubMed 24075141Pedersen 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.
- Background: PubMed 23316152Whiteley 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.
- Background: PubMed 20406576Whiteley 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.
- Background: PubMed 27039383Jianqin 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.
- Background: PubMed 24986816Ho 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.
- Background: PubMed 25018147Trivedi 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.
- ESPA Research websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Group data will be available upon request
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John K Lodge, PhD principal investigator
Northumbria University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing a2 milk and a1 containing milk in people with Autism and Attention Deficit Hyperactivity Disorder, run by Northumbria University at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Childhood Autism Rating Scale (CARS2-HF) Value during intervention (time frame: Baseline to Week 4 to Week 8). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02911194, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Sep 2018.