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Trial registered on ANZCTR


Registration number
ACTRN12615001121550p
Ethics application status
Submitted, not yet approved
Date submitted
5/10/2015
Date registered
23/10/2015
Date last updated
23/10/2015
Type of registration
Prospectively registered

Titles & IDs
Public title
The Effect of Diet and Nutritional Supplementation on Behaviour, Quantitative Electroencephalography (QEEG) and Cognitive Functioning in Attention Deficit Hyperactivity Disorder (ADHD)
Scientific title
The Effect of Diet and Nutritional Supplementation on Behaviour, Quantitative Electroencephalography (QEEG) and Cognitive Functioning in Children with Attention Deficit Hyperactivity Disorder (ADHD)
Secondary ID [1] 287164 0
Nil
Universal Trial Number (UTN)
U1111-1173-6767
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Attention Deficit Hyperactivity Disorder (ADHD) 295732 0
Condition category
Condition code
Mental Health 296010 296010 0 0
Other mental health disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The first appointment involved in the trial is with Dr Jacques Duff. He will explain the dietary and nutritional supplementation requirements of the study to parents of participants and answer any questions they may have about the treatment protocol. Dr Duff is a Registered Psychologist and also Neuroscientist and Nutritionist. Participants will be asked to not start their child on the diet and supplements until after their next visit (where all baseline testing will take place). He will also provide parents with a kit and instructions on how to collect a faecal sample from your child that will be sent by courier to Bioscreen Medical for analysis.

Please see the attached nutrition form for details about the administration and dosage requirements for the nutritional supplements in the study.

The 6 month dietary alteration period eliminates all additives, preservatives, food colourings, gluten (in particular wheat), dairy products, cereal grains, excess sugar and refined carbohydrates. Patients are encouraged to eat more fish, fruit, vegetables, legumes, pulses and selenium containing foods (e.g., Brazil nuts). They are also encouraged to eat eggs, beef, free range chicken and goats meat in moderation. The nutritional supplementation includes Fish oils, zinc citrate, vitamin E, magnesium, cognisense, vitamin C and vitamin D3.

As outlined in the Information to Participants in Research document, dietary compliance will be monitored by at each of the bimonthly appointments at the clinic and by parents via a monthly diary which will be made available either online or hard copy.
Intervention code [1] 292439 0
Treatment: Other
Intervention code [2] 292606 0
Lifestyle
Comparator / control treatment
The proposed study will not be using a control group. All participants baseline scores will be compared at a 6 month follow up assessment.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 295853 0
Primary Outcome 1: Quantitative Electroencephalography (QEEG) observed changes in Theta power.
Timepoint [1] 295853 0
Timepoint: Baseline and at 6 month follow up.
Primary outcome [2] 295856 0
Primary Outcome 2: Changes in Faecal Microbial Analysis results (including count of bacteria such as Streptococcus, E.coli and Enterococcus).
Timepoint [2] 295856 0
Timepoint: Baseline and at 6 month follow up.
Primary outcome [3] 296355 0
Primary Outcome 3: Mean score changes on the Test of Variables of Attention.
Timepoint [3] 296355 0
Baseline and 6 month follow up.
Secondary outcome [1] 316723 0
Secondary Outcome 1: Actigraphy (using an Actiwatch) measuring sleep efficiency.
Timepoint [1] 316723 0
Timepoint: Baseline and at 6 month follow up.
Secondary outcome [2] 316724 0
Secondary Outcome 2: Inattention, hyperactivity/impulsivity, learning problems, executive functioning, aggression, and peer relations assessed by Conners Rating Scales, 3rd Edition.
Timepoint [2] 316724 0
Timepoint: Baseline and at 6 month follow up.
Secondary outcome [3] 316725 0
Secondary Outcome 3: ADHD Rating Scale.
Timepoint [3] 316725 0
Timepoint: Baseline and at 6 month follow up.
Secondary outcome [4] 316726 0
Secondary Outcome 4: Diet Compliance, made available online or hard copy for parents to complete on a monthly basis..
Timepoint [4] 316726 0
Timepoint: Baseline and at one month intervals for a period of 6 months.
Secondary outcome [5] 316727 0
Secondary Outcome 5: Test of Everyday Attention for Children subtests.
Timepoint [5] 316727 0
Timepoint: Baseline and at 6 month follow up.
Secondary outcome [6] 318232 0
Primary outcome - Quantitative Electroencephalography (QEEG) observed changes in Delta power.
Timepoint [6] 318232 0
Baseline and at 6 month follow up.
Secondary outcome [7] 318233 0
Primary outcome - Quantitative Electroencephalography (QEEG) observed changes in Beta power.
Timepoint [7] 318233 0
Baseline and 6 month follow up.
Secondary outcome [8] 318234 0
Primary outcome - Quantitative Electroencephalography (QEEG) observed changes in Alpha power.
Timepoint [8] 318234 0
Baseline and 6 month follow up.

Eligibility
Key inclusion criteria
Participants will be required to have a diagnosis of Attention Deficit Hyperactivity Disorder (ADHD) according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). People with ADHD display persistent patterns of inattention and/or hyperactivity-impulsivity that interferes with functioning or development.
Minimum age
6 Years
Maximum age
13 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
No significant co-morbidities (for example a diagnosis of autism or depression as well as ADHD).

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
All participants will be allocated to the treatment group.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
After parental consent is obtained participants will be asked to attend 6 visits at the Behavioural Neurotherapy clinic across six months for this study. At the first clinic appointment the treatment regime (diet and nutritional supplements - details provided in Step 3 - Intervention/Exposure of this application) will be explained by clinician Dr Jacques Duff. This appointment will take 60 minutes. Parents will be asked not to begin the diet/nutrition intervention until after baseline evaluations have been completed (at the next session). The Bioscreen FMA kit will also be provided at this initial
appointment, to be taken and sent to Bioscreen Medical for analysis on the morning of their baseline evaluation session. Please refer to the attached FMA procedure protocol for detailas regarding the collection of the faecal sample.
The second visit will take place within 14 days of the fist visit, and this is when baseline evaluations will take place. In reality we will attempt to arrange the second appointment as quickly as possible after the first so that the treatment can begin with minimum delay. This is only restricted by parent availability. This session will include QEEG (45-60 minutes) followed by cognitive testing (TOVA and selected subtests of the TEA-Ch) (45-60 minutes).
Subsequent to the baseline evaluation, the 6 month dietary alteration and nutritional supplementation period will commence. Once the 6 month dietary and nutritional intervention has begun, parents will be requested to make 3 appointments (once every 8 weeks) at the Behavioural Neurotherapy Clinic with Dr Jacques Duff for treatment monitoring. Dr. Duff will discuss diet compliance (participants will also be given a short dietary compliance questionnaire to complete) and any challenges participants may be facing throughout the treatment period at these appointments. The post-treatment evaluation will occur after the 6 month protocol. This follow up assessment will include the same evaluations as the baseline After this session participation in the study will cease. Should patients wish to continue to see Dr Duff then this would be done at their own volition and under the usual fee structure.
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Practical, financial and statistical considerations have been taken into account regarding the selection of 30 participants for this study. The study will help provide useful information regarding the outcome measures used, including effect sizes that will be useful in informing future studies. Therefore it is considered a feasibility study for future clinical trials.

Power analysis for the combined total group (analysis conducted on G*Power 3.1) show that with a sample size of 30 (alpha = .05,
power = 0.8) large effect sizes will achieve significance using a variety of tests: t-tests difference between two dependent means
(dz = 0.5) and Wilcoxon non-parametric test (dz = 0.5).

These analyses will be used to explore differences in cognitive results, QEEG, questionnaires and actigraphy data due to dietary alterations and nutritional supplementation in the data collected from the two evaluations.

Stool samples will be analysed using the FMA test. This analysis uses a stool sample to culture, identify and quantify faecal bacteria with a focus on anaerobic and aerobic microflora and yeasts. Participants will be categorized as to their response to specific microbiota. Inferential statistics as outlined above will also be used to explore these changes. Past investigations using FMA in a different population suggest that this data may not be normally distributed, in which case noninferential statistics (e.g. Mann Whitney test) will be used.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
6/11/2015
Actual
Date of last participant enrolment
Anticipated
27/05/2016
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
30
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 292166 0
Charities/Societies/Foundations
Name [1] 292166 0
Australian Autism ADHD Foundation
Country [1] 292166 0
Australia
Primary sponsor type
University
Name
Victoria University
Address
Ballarat Road, Footscray, VIC, 3011
Country
Australia
Secondary sponsor category [1] 290839 0
None
Name [1] 290839 0
Address [1] 290839 0
Country [1] 290839 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 293455 0
The Victoria University Human Research Ethics Committee
Ethics committee address [1] 293455 0
Ballarat Road, Footscray, VIC, 3011.
Ethics committee country [1] 293455 0
Australia
Date submitted for ethics approval [1] 293455 0
26/09/2015
Approval date [1] 293455 0
Ethics approval number [1] 293455 0

Summary
Brief summary
There is now a growing amount of research supporting the notion of communication between gut microbiota (microorganisms; e.g. ecoli, streptococcus) and the central nervous system (CNS) (known as the brain-gut axis). According to Cryan and Dinan (2012) communication between the gut and CNS may be occurring through neural, endocrine and immune pathways indicating the possibility of alterations to gut microbiota as a form of therapy for treatment of CNS related disorders. According to a review by Kidd (2000) integrative
treatments such as correction of intestinal dysbiosis, nutritional supplementation and dietary modifications can be a successful way to help children with ADHD reduce symptoms and move towards a productive and normal life. A review by Stevens, Kuczek, Burgess, Hurt, and Arnold (2011) states that there are a number of studies that have found encouraging results in ADHD children following an elimination diet (Pelsser et al., 2011; Pelsser et al., 2009) and diets challenging with or removing any artificial food dyes (Bateman et al., 2004; McCann et al., 2007). This review supported the use of dietary interventions in at least subpopulations of ADHD children, concluding diets that removed artificial colours significantly improve symptoms that return when challenged (Stevens et al., 2011). These authors also concluded that elimination diets would be an appropriate intervention for children who have not responded satisfactorily to traditional treatment. Moreover, Villagomez and Ramtekkar (2014) concluded that the use of nutritional supplementation in children with ADHD may be a justified and importantly safe intervention, where a number of studies have observed improvements in ADHD related symptomatology following nutritional supplementation (Bilici et al., 2004; Harding, Judah,& Gant, 2003; Hawkey & Nigg, 2014; Huss, Volp, & StaussGrabo, 2010). Further, due to the understanding of the microbiome’s connection to neurodevelopment, it is compelling to consider the role it is likely to play in disorders such as ADHD (Theije et al., 2014). Unlike autism spectrum disorders (ASDs), there have been no studies investigating the microbial composition and status of ADHD children, which could help provide some important insights into the effects of food or food allergy on behaviour (Theije et al., 2014).

Previously no study has investigated the effects of diet and nutrition upon psychological functioning (cognition, brain activity, and sleep), together with gut microbial composition in this population. This is important because investigations of gut composition have to date largely been ignored in children with ADHD (Theije et al., 2014) and this information could be used as an important indicator to guide clinical decisions on an individualised level. Although this study is applying a standardised protocol in the interests of experimental control, this information could still be important for future individualized treatments.
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 572 572 0 0
/AnzctrAttachments/368865-ADHD Consent Form final 1.docx
Attachments [2] 573 573 0 0
/AnzctrAttachments/368865-ADHD Participant Info final.docx
Attachments [3] 574 574 0 0
/AnzctrAttachments/368865-Test ProceduresFinal.docx
Attachments [4] 575 575 0 0
/AnzctrAttachments/368865-ADHD References.docx
Attachments [5] 576 576 0 0
/AnzctrAttachments/368865-ADHD Advertisement.docx
Attachments [6] 577 577 0 0
/AnzctrAttachments/368865-Section 7 Supplement Attachment.docx
Attachments [7] 578 578 0 0
/AnzctrAttachments/368865-Updated Nutrition Form JH2.docx

Contacts
Principal investigator
Name 58518 0
Dr Michelle Ball
Address 58518 0
Victoria University, Ballarat Road, Footscray, VIC, 3011
Country 58518 0
Australia
Phone 58518 0
+61 3 9919 2536
Fax 58518 0
Email 58518 0
[email protected]
Contact person for public queries
Name 58519 0
Jordan Hince
Address 58519 0
Victoria University, Ballarat Road, Footscray VIC 3011
Country 58519 0
Australia
Phone 58519 0
+61 433 641 687
Fax 58519 0
Email 58519 0
[email protected]
Contact person for scientific queries
Name 58520 0
Michelle Ball
Address 58520 0
Victoria University, Ballarat Road, Footscray, VIC, 3011
Country 58520 0
Australia
Phone 58520 0
+61 3 9919 2536
Fax 58520 0
Email 58520 0
[email protected]

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