AzTrials
AzTrials

Attention Deficit-Hyperactivity DisorderBRAINNCT03440346

Biomarker Research in ADHD: the Impact of Nutrition

A study testing Few-foods diet in people with Attention Deficit-Hyperactivity Disorder, run by Wageningen University at 1 site in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Attention deficit hyperactivity disorder (ADHD) is the most common childhood behavioural disorder, causing significant impediment to a child's development. The exact aetiology of ADHD is still unknown. It is a complex disorder with numerous contributing (epi)genetic and environmental factors. Read more about this study

Who is it for?
Ages 8 to 10 years, men only
Conditions the study is for
Attention Deficit-Hyperactivity Disorder
What is being tested?
Few-foods diet
Could I receive a placebo?
No, everyone receives an active treatment
How many people
100 participants
Where
1 siteNetherlands
Study dates
19 Feb 2018to 21 Jun 2019
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 8 to 10 years
  • Men only
  • No healthy volunteers
  • Child

Who may be able to join

  • Meeting DSM-IV ADHD criteria
  • Male
  • Aged 8 up to and including 10 years
  • Right-handed
  • Available to visit Wageningen University for 4 sessions (i.e. intake, screening, T1 and T2), of which 3 sessions including the child (screening, T1, T2)
  • Upon study start, fully understanding and agreeing to the study objectives and having dated and signed an informed consent to participate in the study, including permission that material will be used or archived for (epi)genetic testing
  • Willing to be informed about chance-findings that may have implications for the health of the child or his family, and approving of reporting this to the child's medical specialist or family's general physician.
  • If the child uses "over the counter" medication, e.g. laxatives, melatonin for sleeping problems or hay fever medication, parents are asked to share the information leaflet, and if necessary participants are asked to change to alternatives that are free of additives that may affect ADHD, e.g. laxatives free of artificial sweeteners, sugar and cacao.

Who cannot join

  • Diagnosis Autism Spectrum Disorder
  • Diagnosis Developmental Coordination Disorder
  • Premature birth (< 36 weeks) and/or oxygen deprivation during birth
  • Diagnosed chronic gastrointestinal disorder, i.e. inflammatory bowel disease, irritable bowel syndrome, celiac disease, non-celiac gluten-intolerance (gluten-sensitivity) or lactose-intolerance
  • Auto-immune disorder (e.g. diabetes mellitus type 1)
  • Vegetarian/vegan
Show all 15Show fewer
  • Diagnosis dyslexia and/or dyscalculia
  • IQ < 85
  • Following behavioural therapy
  • Use of ADHD medication
  • Use of systemic antibiotics, antifungals, antivirals or antiparasitics in the past six months
  • Insufficient command of the Dutch language by either parents or child that may affect understanding and execution of study and dietary instructions
  • Family circumstances that may compromise following or completion of the diet, including but not limited to family relational problems
  • Having a contra-indication to MRI scanning (including, but not limited to): pacemakers and defibrillators, intraorbital or intraocular metallic fragments, ferromagnetic implants, claustrophobia.
  • Two weeks prior to the start of the study, dietary supplements (e.g. antioxidants, minerals, vitamins) or pro- or prebiotics use has to be stopped.

Trial locations and contacts

1 site in 1 country.

Netherlands1 site
  • Wageningen University

    Wageningen

Other trials in Netherlands

About this study

Official title: Biomarker Research in ADHD: the Impact of Nutrition (BRAIN). An Open-label Trial to Investigate the Mechanisms Underlying the Effects of a Few-foods Diet on ADHD Symptoms in Children

Attention deficit hyperactivity disorder (ADHD) is the most common childhood behavioural disorder, causing significant impediment to a child's development. The exact aetiology of ADHD is still unknown. It is a complex disorder with numerous contributing (epi)genetic and environmental factors. Currently, treatment predominantly consists of behavioural and pharmacological therapy. However, medication use is associated with several side effects and concerns about long-term effects and efficacy exist. Therefore, there is considerable interest in the development of alternative treatment options.

Double-blind research investigating the effect of a few-foods diet (FFD) has demonstrated large improvements in ADHD symptoms. However, following an FFD requires great effort of both the child and parents. To make this treatment easier or potentially obsolete, it is important to understand how and in which children an FFD affects ADHD symptoms.

Read more

The investigators hypothesise that an FFD affects brain function and behaviour, including ADHD symptoms, via the complex network of communication between the microbiota, gut and brain, i.e. the MGB axis. The aim of this study is to identify potential mechanism(s) underlying the impact of an FFD on ADHD symptoms and to identify biomarkers that predict the response to the FFD.

100 boys with ADHD will follow the FFD for 5 weeks. After inclusion, all participants will start with a baseline period, during which they will maintain their regular diet. The baseline period ends at the end of week 2. Thereafter, participants will follow a 5-week FFD, preceded by a 1-week transition period. The FFD period ends at the end of week 8.

At the end of the baseline period (i.e. at the end of week 2) and at the end of the FFD (i.e. at the end of week 8), fMRI scans will be made, blood and buccal saliva will be collected, and stool and urine will be handed in. Children will do computer tasks and parents will complete questionnaires to monitor ADHD and physical complaints. All samples will be analysed by researchers blinded to behavioural responses to the FFD. To assess the impact of the FFD on brain function and the MGB axis, associations between ADHD behavioural changes and changes in other primary and secondary study outcomes will be analysed.

This study may lead to the identification of biomarkers that can predict the response to an FFD. Understanding which changes - induced by an FFD - lead to improvements in ADHD symptoms may provide new avenues for developing treatments. Ultimately, the findings may enable personalised intervention strategies based on an individuals' configuration of the MGB axis.

Being tested
Few-foods diet
Keywords
Attention Deficit Hyperactivity Disorder, ADHD, child, human, diet, few-foods diet, brain, gut, microbiota
Medical subject headings
Attention Deficit Disorder with Hyperactivity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Few-foods dietOther

    Also called Restricted Elimination Diet

    The few-foods diet (FFD) is followed for 5-weeks preceded by a 1-week transition period during which the child's eating pattern will be gradually adjusted. The diet consists of rice, meat (turkey and lamb), a range of vegetables, pear, rice milk with added calcium and water, and is complemented with foods such as potatoes, fruits, corn, some sweets and wheat, which are allowed in small quantities only. Normal quantities of vegetables, rice and meat are allowed every day. If necessary the diet will be adjusted to avoid foods that the child dislikes or has cravings for. If the child does not respond to the initial FFD, i.e. no change in behaviour after the first two weeks, interim adjustments to the FFD will be made in consultation with the parents.

Study groups in NCT03440346
Study groupRoleWhat they receive
Few-foods diet interventionExperimentalNot described
Receives: Other: Few-foods diet

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in neural activation patterns during execution of tasks

    Using fMRI, blood oxygen-level-dependent (BOLD) signal changes will be measured whilst performing cognitive tasks that assess inhibitory control and selective attention, i.e. a stop-signal task (response inhibition) and a Flanker task (response conflict and associated error monitoring). fMRI BOLD responses will be assessed between variable task-elements and performance. Region of interest (ROI; anatomically defined regions in the brain) analyses of the BOLD responses will be performed.

    Measured: Before and at the end of the FFD intervention (i.e. at the end of week 2 and at the end of week 8)

  2. Change in peripheral blood metabolite concentrations

    Global metabolite profiles will be examined in plasma (or alternatively serum) obtained from whole blood using mass-spectrometry profiling. Phenylalanine and tyrosine plasma levels represent primary outcomes.

    Measured: Before and at the end of the FFD intervention (i.e. at the end of week 2 and at the end of week 8)

  3. Change in functional composition of the gut microbiota

    Metagenome profiling will be performed on stool samples, leveraging Illumina next-generation sequencing technology. Sequence read data will be used for abundance profiling of microbiota genes that encode enzymes directly involved in the production or degradation of the dopamine and noradrenaline precursors phenylalanine and tyrosine.

    Measured: Before and at the end of the FFD intervention (i.e. at the end of week 2 and at the end of week 8)

  4. Change in ADHD symptom scores

    ADHD symptoms will be scored using the 18-item ADHD rating scale, which is based on the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV and consists of 9 items that assess inattention and 9 items that focus on hyperactivity and impulsivity.

    Measured: Before and at the end of the FFD intervention (i.e. at the end of week 2 and at the end of week 8)

Secondary outcomes (15)
  1. Change in whole brain neural activation patterns during the execution of tasks

    fMRI BOLD responses, assessed between variable task-elements, will be explored using whole brain imaging analyses.

    Measured: Before and at the end of the FFD intervention (i.e. at the end of week 2 and at the end of week 8)

  2. Change in whole brain functional connectivity at rest

    A resting-state fMRI scan will be performed to analyse the networks of brain structures that are active during the resting-state.

    Measured: Before and at the end of the FFD intervention (i.e. at the end of week 2 and at the end of week 8)

  3. Change in taxonomic and functional composition of the gut microbiota

    Stool metagenome and/or 16S ribosomal ribonucleic acid (rRNA) gene profiling will be performed using Illumina sequencing. Metagenome data will be used to determine the taxonomic and functional composition of the gut microbiota.

    Measured: Before and at the end of the FFD intervention (i.e. at the end of week 2 and at the end of week 8)

  4. Change in metabolite profiles

    Global metabolite profiles will be examined in plasma (or alternatively serum) obtained from whole blood, urine and optionally in stool using mass-spectrometry profiling.

    Measured: Before and at the end of the FFD intervention (i.e. at the end of week 2 and at the end of week 8)

  5. Change in peripheral blood cell gene expression profiles

    Peripheral blood mononuclear cells will be isolated from fasting blood samples and gene expression profiles will either be determined using Affymetrix gene expression arrays or by RNA-sequencing.

    Measured: Before and at the end of the FFD intervention (i.e. at the end of week 2 and at the end of week 8)

  6. Change in a panel of peripheral blood protein biomarkers related to immune, metabolic and neurological status

    A large panel of proteins will be profiled using quantitative immunoassays or proteomics on blood plasma or serum.

    Measured: Before and at the end of the FFD intervention (i.e. at the end of week 2 and at the end of week 8)

  7. DNA genotype

    Genotyping will be conducted using a microarray platform on DNA isolated from buccal cells or on DNA isolated from whole blood.

    Measured: Before the FFD diet intervention (i.e. at the end of week 2)

  8. Change in DNA methylation profiles

    Genome-wide profiling of DNA methylation status will be conducted using the Illumina Infinium MethylationEPIC beadchip microarray platform in DNA isolated from buccal cells or alternatively on DNA isolated from whole blood.

    Measured: Before and at the end of the FFD intervention (i.e. at the end of week 2 and at the end of week 8)

  9. Change in executive function

    Executive functioning will be measured using a continuous performance test that assesses executive functions such as sustained attention and behavioural inhibition.

    Measured: Before and at the end of the FFD intervention (i.e. at the end of week 2 and at the end of week 8)

  10. Change in ADHD symptoms

    Change will be scored using the Abbreviated Conners' scale

    Measured: Before and at the end of the FFD intervention (i.e. at the end of week 2 and at the end of week 8)

  11. Change in oppositional defiant disorder symptoms

    Change will be scored using a validated questionnaire.

    Measured: Before and at the end of the FFD intervention (i.e. at the end of week 2 and at the end of week 8)

  12. Change in social behavioural problems

    Change will be scored using the children's social and behavioural questionnaire.

    Measured: Before and at the end of the FFD intervention (i.e. at the end of week 2 and at the end of week 8)

  13. Change in physical complaints

    Change will be scored using a validated questionnaire.

    Measured: Before and at the end of the FFD intervention (i.e. at the end of week 2 and at the end of week 8)

  14. Change in stool frequency

    The child will record the frequency of defaecations for one week.

    Measured: Before and at the end of the FFD intervention (i.e. at the end of week 2 and at the end of week 8)

  15. Change in stool type

    The child will type each stool using the modified Bristol stool scale form for children, which comprises 5 stool form types described and depicted in drawings.

    Measured: Before and at the end of the FFD intervention (i.e. at the end of week 2 and at the end of week 8)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Feb 2018
  2. Study start19 Feb 2018
  3. Primary completion21 Jun 2019
  4. Study completion21 Jun 2019

Resources

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
Basic science
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
100 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03440346
Sponsor's protocol ID
NL63851.081.17
Acronym
BRAIN
Status last verified
Jun 2019
First submitted
19 Jan 2018
Last updated
1 Jul 2019
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Pelsser LM, Frankena K, Toorman J, Savelkoul HF, Dubois AE, Pereira RR, Haagen TA, Rommelse NN, Buitelaar JK. Effects of a restricted elimination diet on the behaviour of children with attention-deficit hyperactivity disorder (INCA study): a randomised controlled trial. Lancet. 2011 Feb 5;377(9764):494-503. doi: 10.1016/S0140-6736(10)62227-1.

    PubMed 21296237
  • Pelsser LM, Frankena K, Toorman J, Rodrigues Pereira R. Diet and ADHD, Reviewing the Evidence: A Systematic Review of Meta-Analyses of Double-Blind Placebo-Controlled Trials Evaluating the Efficacy of Diet Interventions on the Behavior of Children with ADHD. PLoS One. 2017 Jan 25;12(1):e0169277. doi: 10.1371/journal.pone.0169277. eCollection 2017.

    PubMed 28121994
  • Stobernack T, de Vries SPW, Rodrigues Pereira R, Pelsser LM, Ter Braak CJF, Aarts E, van Baarlen P, Kleerebezem M, Frankena K, Hontelez S. Biomarker Research in ADHD: the Impact of Nutrition (BRAIN) - study protocol of an open-label trial to investigate the mechanisms underlying the effects of a few-foods diet on ADHD symptoms in children. BMJ Open. 2019 Nov 5;9(11):e029422. doi: 10.1136/bmjopen-2019-029422.

    PubMed 31694844

Questions about this trial

What is this clinical trial studying?

A study testing Few-foods diet in people with Attention Deficit-Hyperactivity Disorder, run by Wageningen University at 1 site in Netherlands.

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 8 inclusion and 15 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 1 Jul 2019. 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 Netherlands. 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. 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 neural activation patterns during execution of tasks (time frame: Before and at the end of the FFD intervention (i.e. at the end of week 2 and at the end of week 8)). The study lists 4 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 NCT03440346, which also lists 3 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 1 Jul 2019.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in