Probiotic Supplementation in Children With ADHD

Study Overview
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Brief Summary
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This randomised, placebo controlled trial explores the effects of supplementation with a probiotic drink (kefir) in children diagnosed with ADHD on behaviour, sleep, attention and the gut microbiome.

Detailed Description
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Children with Attention Deficit Hyperactivity Disorder (ADHD) can suffer debilitating symptoms, including problematic behaviour and sleep. Dietary manipulations may be a helpful treatment option for children, but the most effective are highly restrictive, with little known about why they might work. Optimising gut bacteria may help alleviate some of the symptoms of this condition via the gut-brain-axis. The consumption of a probiotic fermented drink (kefir) can positively influence composition of gut bacteria. The purpose of this study is to explore the effects of supplementation of a probiotic drink (kefir) on behaviour, sleep, attention and the gut microbiome in children diagnosed with ADHD. In a six-week randomised controlled double-blind, placebo controlled trial, 70 children diagnosed with ADHD (aged 8-13 years) will be randomised to be given either a probiotic drink (kefir) or a placebo drink. At the beginning and the end of the study a combination of questionnaires, cognitive assessment, sleep/physical activity measures and microbiome analysis will be employed to assess the effect of kefir consumption on symptoms of ADHD and the gut microbiome.

Official Title
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A Randomised Controlled Trial of the Effects of a Probiotic Drink on Behaviour, Sleep and the Microbiome in Children With ADHD

Conditions
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ADHD

Intervention / Treatment
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* Dietary Supplement: Experimental: Kefir probiotic drink (supplied by Nourish)
* Dietary Supplement: Placebo comparator


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A previous diagnosis of ADHD according to the DSM-IV or DSM-V criteria by a qualified health care professional. Children aged between 8 and 13 years at the time of study. Children with a comorbidity will be accepted. Both males and females Exclusion Criteria: Children currently undergoing a current course of behavioural therapy. Children with a reported milk allergy or lactose intolerance. Reported use of antibiotics, probiotics, antifungals or steroids in the past four weeks. Diagnosis of a gastrointestinal disorder e.g., Inflammatory Bowel Disease or Coeliac disease. Diagnosis of an auto-immune disease or compromised immunity.

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 13 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomised double-blind quantitative repeated measures design
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Kefir probiotic drink<br>Daily kefir for 6 weeks. | Dietary Supplement: Experimental: Kefir probiotic drink (supplied by Nourish)<br>* 125ml per day of dairy based probiotic drink (Kefir) containing ≥ 50billion colony forming units (CFU), supplied in plain packaging.<br>|
| Placebo Comparator: placebo comparator<br>Daily non-fermented dairy based equivalent drink for 6 weeks. | Dietary Supplement: Placebo comparator<br>* 125ml of non-fermented dairy based placebo (UHT milk) per day, supplied in plain packaging.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in The Strengths and Weakness of ADHD-symptoms and Normal-behaviour (SWAN) scale | 18 item scale comparing the child to other children of the same age. Each item is responded to on a seven-point scale ranging from far below average (-3) to far above average (+3). The scores are summed and divided by the number of items, to express the summary score as the average rating-per-item (range -3 to +3, with lower scores indicating more severe ADHD symptoms). | week 0 and week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in The Go/NoGo test | Participants respond to a particular stimulus while various stimuli are presented on a computer screen. There are 1500 milliseconds between each response, with 320 repetitions. Go errors (errors of omission) - A higher score = greater inattention (worse) NoGo errors (errors of commission) - A higher score = greater impulsivity (worse) Go reaction times - A higher score = less impulsivity (better) Go reaction time variability - A higher score = greater inattention (worse) | week 0 and week 6 | 
| Change in mean activity during sleep. | Actigraphy recordings. Range 0-∞. A higher score = less sound sleep (worse). | week 0 and week 6 | 
| Change in minutes spent awake during the down period | Actigraphy recordings. Range 0-∞. A higher score = less sound sleep (worse). | week 0 and week 6 | 
| Change in sleep latency | Actigraphy recordings of time taken to fall asleep. Range 0-∞. A higher score = more time taken to fall asleep (worse). | week 0 and week 6 | 
| Change in sleep efficiency | Actigraphy recordings of % down period spent asleep, after removing sleep latency. A higher score = better. | week 0 and week 6 | 
| Change in wake after sleep onset | Actigraphy recordings of minutes spent awake during the down period after removing sleep latency. Range 0-∞. A higher score = less sound sleep (worse). | week 0 and week 6 | 
| Change in sleep fragmentation | Actigraphy recordings of the number of awakenings/ total minutes of sleep x 100) - Higher score = more fragmented sleep (worse). | week 0 and week 6 | 
| Change in mean daytime activity | Actigraphy recording of mean daytime activity. (0-∞) not necessarily worse or better. | week 0 and week 6 | 
| The Consensus Sleep diary | Record of sleep - used qualitatively to detect and remove artefacts from the data. Takes approximately 3 minutes per day to complete. | week 0 and week 6 | 
| The Consensus Sleep diary | Record of sleep - used qualitatively to detect and remove artefacts from the data. Takes approximately 3 minutes per day to complete. | week 6 | 
| Change in The Child's Sleep habits questionnaire | Consists of 33 items. Each item is rated by parents using a three-point scale (with some items reverse-scored): 3 - Usually =occurs 5+ times a week 2 - Sometimes = occurs 2-4 times a week 1 - Rarely = occurs 0-1 times a week A Total Sleep Disturbances score is calculated as the sum of all scored questions. Total scores range from 33 to 99 - higher scores indicate more problematic sleep. | week 0 and week 6 | 
| Change in Sleep self report | Consists of 26 items. Each item is rated by children using a three-point scale (with some items reverse-scored): 3 - Usually = occurs 5+ times a week 2 - Sometimes = occurs 2-4 times a week 1 - Rarely = occurs 0-1 times a week. A Total Sleep Disturbances score is calculated as the sum of all scored questions. Total scores range from 26 to 78 - higher scores indicate more problematic sleep. | week 0 and week 6 | 
| Change in The Gastrointestinal Severity Index | A three-point rating scale across six gastrointestinal symptoms. A higher scores indicate worse symptoms. Total scores range from 0-12 - higher scores indicating more severe symptoms. | week 0 and week 6 | 
| Change in stool microbiome analysis | Investigate if there are changes in diversity and species in week 6 relative to week 0. | week 0 and week 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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microbiome, ADHD, probiotic, Kefir