Contact information
Type
Scientific
Primary contact
Mrs Lidy Pelsser
ORCID ID
Contact details
ADHD Research Centre
Liviuslaan 49
Eindhoven
5624 JE
Netherlands
incastudie.cbi@wur.nl
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
SKN-18511/3/19; SNO-T-0602-48
Study information
Scientific title
A Dutch randomised controlled trial into the effects of food on the behaviour of a random
group of school-going children meeting the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria for Attention-Deficit Hyperactivity Disorder (ADHD), including immunological testing
Acronym
INCA
Study hypothesis
Attention-Deficit Hyperactivity Disorder (ADHD) is a psychiatric disorder which affects 3 to 5% of all school-going children. The disorder generally manifests itself before the age of 7 and is characterised by symptoms of inattention, impulsive behaviour and hyperactivity. ADHD is generally diagnosed in combination with other psychiatric disorders such as Oppositional Defiant Disorder (ODD) and Conduct Disorder (CD).
The trial is two-phased, an elimination phase and a reintroduction phase.
The objective of the elimination phase is to determine the impact of an elimination diet on the behaviour of a heterogeneous, random group of children with ADHD. The null hypothesis is that there is no effect of treatment (i.e. food elimination) on the behavioural scores of the subjects.
The objective of the reintroduction phase is to examine whether Immunoglobulin G (IgG) and Immunoglobulin E (IgE) blood testing is useful in children with ADHD and whether the determination of antibodies to specific foods may simplify the diagnostic procedure in children responding to an elimination diet. The null hypothesis is that there is no effect of treatment, i.e. there is no relationship between the level of IgE or IgG antibodies in the blood and the behavioural scores of the subjects.
Please note that this is a follow-up study to the previously registered trial entitled 'A randomised, controlled study into the effects of food on the behaviour of young children with attention-deficit hyperactivity disorder' [ISRCTN47247160] - see http://www.controlled-trials.com/ISRCTN47247160.
Please note that as of 23/09/08 this trial record was updated. The initial anticipated start and end dates of this trial was as follows:
Initial anticipated start date: 01/02/2008
initial anticipated end date: 01/02/2011
All other changes to this record can be found in the relevant field.
Ethics approval
Ethics approval received from the Medical Ethics Committee of the Wageningen University on the 13th November 2007 (ref: ABR NL 12736.081.06).
Study design
The INCA study is a randomised, controlled, single-blind, multicentre, interventional study.
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Other
Trial type
Treatment
Patient information sheet
Patient information material can be found at the trial website: http://www.incastudie.nl (Dutch only)
Condition
Attention-deficit hyperactivity disorder (ADHD)
Intervention
Current interventions as of 23/09/2008:
All children will be randomly assigned to either a diet group or a control group. Each group consists of 50 children. From each child at least two blood samples will be taken, at the start and at the end of the trial.
Following a baseline period (week 1 - 3), the control group will be placed on a waiting list and will receive no treatment (week 3 - 9). They will receive broad recommendations for a healthy diet. Both groups have to keep an extended diary. The diet group will receive the active treatment, a five weeks elimination diet (week 3 - 9). All major allergen foods, ingredients and/or additives associated with behavioural disorders are eliminated from the diet. The diet basically consists of bread, rice, corn, turkey, lamb, various vegetables and fruits, rice milk with extra calcium, margarine, and pear juice from concentrate. This basis is complemented with specific foods like potatoes, fruits, corn, some sweets and wheat, allowed in limited doses twice a week. Vegetables, fruits, rice and meat are allowed every day. Occasionally the diet will be varied to avoid foods for which the child has a particular craving or dislike. The diet clearly prescribes for each day which products and snacks the child may eat and drink. The diet is adjusted to the individual child in order to take into account the childs specific food preferences and to leave out all foods which the child does not like. If the diet does not result in any behavioural changes after the first two weeks, the diet will be further restricted in consultation with the parents. In the end, therefore, the diet may vary for each individual child, depending on the need to make interim adjustments.
The reintroduction phase (week 9 - 13), is based on the IgE and IgG levels, determined in the first blood test. The control group is still on the waiting list (week 9 - 13), the responders of the diet group will proceed with the reintroduction phase during which all foods with IgG-0 value and without increased IgE level will be reintroduced concurrently to the diet of the responders, in a double-blind cross over design.
Following the final measurements at week 13, all children from the control group will be offered an opportunity to start the elimination diet.
Initial interventions:
All children will be randomly assigned to either a diet group or a control group. Each group consists of 50 children. From each child at least two blood samples will be taken, at the start and at the end of the trial.
Following a baseline period (week 1 - 3), the control group will be placed on a waiting list and will receive no treatment (week 3 - 9). They will receive broad recommendations for a healthy diet. Both groups have to keep an extended diary. The diet group will receive the active treatment, a five weeks elimination diet (week 3 - 9). All major allergen foods, ingredients and/or additives associated with behavioural disorders are eliminated from the diet. The diet basically consists of bread, rice, corn, turkey, lamb, various vegetables and fruits, rice milk with extra calcium, margarine, and pear juice from concentrate. This basis is complemented with specific foods like potatoes, fruits, corn, some sweets and wheat, allowed in limited doses twice a week. Vegetables, fruits, rice and meat are allowed every day. Occasionally the diet will be varied to avoid foods for which the child has a particular craving or dislike. The diet clearly prescribes for each day which products and snacks the child may eat and drink. The diet is adjusted to the individual child in order to take into account the childs specific food preferences and to leave out all foods which the child does not like. If the diet does not result in any behavioural changes after the first two weeks, the diet will be further restricted in consultation with the parents. In the end, therefore, the diet may vary for each individual child, depending on the need to make interim adjustments.
The reintroduction phase (week 9 - 13), is based on the IgE and IgG levels, determined in the first blood test. The control group is still on the waiting list (week 9 - 13), the responders of the diet group will proceed with the reintroduction phase during which all foods with IgG-0 value and without increased IgE level will be reintroduced concurrently to the diet of the responders.
Following the final measurements at week 13, all children from the control group will be offered an opportunity to start the elimination diet.
Intervention type
Other
Phase
Not Specified
Drug names
Primary outcome measure
The Abbreviated Conners Scale (ACS) and the ADHD Rating Scale (ARS) are the two major rating scales for the outcomes of this study. They will be used during all measurement points, i.e. M1 (week 0), M2 (week 3), M3 (week 9), M4 (week 11) and M5 (week 13).
1. The ACS consists of 10 questions using a 4-point scale. A score of 15 represents two standard deviations above the mean cut-off. Scores can range from 0 to 30. The ACS will be completed by both the parents and the teacher
2. The ARS is based on the DSM-IV and consists of 9 inattention items and 9 hyperactivity/impulsivity items, and uses a 4-point scale. The answers to each question vary from Never or Rarely (0 points), Sometimes (1 point), Often (2 points) to Very Often (3 points). The ARS will be completed by the parents, teachers and the blinded paediatrician
Secondary outcome measures
1. A Structured Psychiatric Interview (SPI), based on DSM-IV criteria, will be used to assess comorbid disorders, like ODD and CD. This interview is taken at M1 (week 0), M3 (week 9) and M5 (week 13) and will be completed by the parents, the teacher and the blinded paediatrician
2. The Strengths and Difficulties Questionnaire (SDQ) is a brief behavioural screening questionnaire, concerning emotional and conduct problems, hyperactivity/inattention, peer relationship and prosocial behaviour. The answers to each question are Not True, Somewhat True or Certainly True. Parents and the childs teacher will fill in the SDQ at M2 (week 3), M3 (week 9) and M5 (week 13)
3. Physical complaints of the child will be identified with the Other Complaints Questionnaire. The questions concern the presence or absence of physical complaints such as gastrointestinal problems, headaches, eczema, unusual perspiration, sleep disturbances and asthma. The answers to each question are Yes (often complaints) or No (seldom or never complaints). Parents must fill in the questionnaire at M2 (week 3), M3 (week 9) and M5 (week 13)
4. All IgG-scores, IgE-scores and other blood values will be analysed
Overall trial start date
01/09/2008
Overall trial end date
01/09/2011
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. ADHD diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV); diagnoses based on structured psychiatric interviews and standard questionnaires (Abbreviated Conners Scale, ADHD Rating Scale, Strengths and Difficulties Questionnaire) to be completed by parents and teachers
2. Children aged between 4 and 8
3. Children not taking medication such as methylphenidate
4. Parental permission for three blood tests
5. Sufficient command of the Dutch language
Participant type
Patient
Age group
Child
Gender
Both
Target number of participants
100
Participant exclusion criteria
1. Family circumstances hampering completion of the elimination diet
2. Children already on a diet or having been on a diet in the past two months
3. Children receiving behavioural therapy or medication at the time of registration
Recruitment start date
01/09/2008
Recruitment end date
01/09/2011
Locations
Countries of recruitment
Netherlands
Trial participating centre
ADHD Research Centre
Eindhoven
5624 JE
Netherlands
Sponsor information
Organisation
Wageningen University (The Netherlands)
Sponsor details
c/o Prof dr H.F.J. Savelkoul
P.O. Box 338
Wageningen
6700 AH
Netherlands
Huub.Savelkoul@wur.nl
Sponsor type
University/education
Website
Funders
Funder type
Research organisation
Funder name
The Nuts-Ohra Foundation (Stichting Nuts Ohra [SNO]) (The Netherlands) (ref: SNO-T-0602-48)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
The Foundation for Childrens Welfare Stamps Netherlands (Stichting Kinderpostzegels Nederland [SKN]) (ref: SKN-18511/3/19)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
1. 2011 results in http://www.ncbi.nlm.nih.gov/pubmed/21296237
Publication citations
-
Results
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, 377, 9764, 494-503, doi: 10.1016/S0140-6736(10)62227-1.