Efficacy of Vivomixx on Behaviour and Gut Function in Autism Spectrum Disorder
Condition: Autism Spectrum Disorder
MeSH terms: Autistic Disorder; Autism Spectrum Disorder; Child Development Disorders, Pervasive
Study type: Interventional

Summary: 
      The purpose of this study is to assess the effects of 3 months supplementation with the multi
      strain probiotic Vivomixx on the overall function, aberrant behaviours and frequency of
      gastrointestinal symptoms in children with Autism Spectrum Disorders and co-morbid
      gastrointestinal symptoms.

      The investigators will also assess the effect of the intervention on parenting stress.

      A further issue will be to identify any predictors of response to the probiotic.

      Finally, the investigators will assess whether there is an association between altered
      behaviour and altered gut function in users of Vivomixx.
    

Detailed description: 
      Potential trial participants will be recruited via one of two routes,

        1. A children's charity will email parents of children with ASD on their database with a
           copy of our recruitment poster and asked to contact us if they wish their child to be
           considered for the study.

        2. Information on the trial was given to attendees of a bi-annual charity conference in
           June 2016 run by Thinking Autism charity, which offers support to parents of children
           with ASD. Contact details were taken from parents who were potentially interested in
           their child taking part. They will be emailed a copy of the recruitment poster and asked
           to contact the investigators if they wish their child to be considered for the study.

      Parents who respond to the recruitment poster will be emailed the Patient Information Sheet
      and the Child Information Leaflet. A few days later, they will then be emailed to ask if they
      are interested in answering some questions to see if their child is eligible for the study.
      If they are, an appointment will be made to phone them and complete the screening
      questionnaire. For those children that fit the requirements for the trial, the parents will
      be invited for their child to take part. The participants recruited to the study will be
      allocated at random to either group A or B and will be given a unique Study Number. All data
      collected throughout the study will be anonymised and identified only by the participant's
      study number.

      The first week of study will be a taste evaluation of the product for all participants (both
      groups). The taste evaluation is to ensure that the participant finds the taste acceptable
      and is willing to take the treatment product. For those that find the taste acceptable they
      will then either receive a 12-week course of Vivomixx probiotic or a 12-week course of the
      placebo powder, according to their random group allocation. The placebo powder has the same
      look and taste as Vivomixx.

      Once the participant has passed the taste evaluation, the child's educator will be sent a
      letter inviting them to participate in the study. Included with this letter will be a consent
      slip, a copy of the Educator Questionnaire and a stamped addressed envelope for returning the
      questionnaires and consent slip to the researcher.

      All participants' parents will be phoned by the researcher in Weeks 5 and 9 to adjust the
      treatment dose, offer support and check compliance.

      Those parents whose child is eligible but who choose not to take part will be asked for the
      main reason and this will be logged in the screening log of patients.

      After 12 weeks there will be 4 weeks when neither group is taking any treatment (a washout
      period). After this, participants who complete all 12 weeks of the double-blind treatment
      period will be eligible to enter the double-blind 12-week withdrawal period. The participants
      that have been taking the placebo will then receive a 12-week course of Vivomixx probiotic.
      The participants that have received Vivomixx, will take a 12-week course of the placebo. All
      participants' parents will be phoned by the researcher in Weeks 21 and 25 to adjust the
      treatment dose, offer support and check compliance. We will also ask about their experience
      of the study.

      The investigators are primarily interested in whether participants in the intervention group
      (Vivomixx) have had more of an improvement in their overall function after their 12-week
      course of Vivomixx compared to that of the control group (receiving the placebo). The
      investigators will also measure the effect of the active treatment on parent stress compared
      to the control group and the effect of the active treatment on gastrointestinal symptoms and
      clinician's global assessment compared to the control group.

      During the study the investigators will assess how well the participants kept to the
      treatment plan. The investigators will also record changes that happen during the trial that
      may affect the efficacy of treatment, for example taking antibiotics or a significant change
      in diet. The investigators will talk to the participant's parents to find how they perceived
      the treatment and how their child tolerated the treatment.

      Statistical methodology and analysis The intention-to-treat (ITT) analysis will be performed
      on all participants who are randomised. An additional analysis will be done on only those
      participants who complete the study per protocol analysis. Details of the statistical
      analysis is given in the Statistical Analysis Plan.
    

Intervention name(s): Vivomixx; Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Multi-strain probiotic containing 450 billion lyophilized bacterial cells per sachet belonging to 8 probiotic strains. The probiotic strains contained in the intervention are Streptococcus thermophilus, Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium infantis, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus paracasei, Lactobacillus delbrueckii subsp. bulgaricus.; 4.4 grams of maltose and silicon dioxide per sachet
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: 3-month randomised controlled cross-over design with 4-week washout. Outcomes measured at baseline and last week of each treatment phase.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Autism; Gastrointestinal; behaviour; constipation; diarrhoea; probiotic; sociability