Trial Outcomes & Findings for Efficacy of Vivomixx on Behaviour and Gut Function in Autism Spectrum Disorder (NCT NCT03369431)

Last Updated: 2022-03-08

Results Overview

The ATEC is a one-page form, designed to be completed by parents, teachers, or caregivers. It consists of 4 subtests: I. Speech/Language Communication (14 items); II. Sociability (20 items); III. Sensory/ Cognitive Awareness (18 items); and IV. Health/Physical/Behavior (25 items). The scale covers 77 items and gives a total score and scores for each of the 4 sub-sections. The higher the score, the greater the impairment overall or in a sub-section. The ATEC total score can range from 0 - 180 and is calculated by summing the scores of each subsection.

Recruitment status

COMPLETED

Study phase

Target enrollment

69 participants

Primary outcome timeframe

ATEC will be measured at the time of enrolment to the study, after the first 12-week treatment and after the second 12-week treatment by the child's primary carer and also by the child's educator.

Results posted on

2022-03-08

Participant Flow

Participant milestones

Participant milestones
Measure	Vivomixx, Then Placebo This group starts with Vivomixx probiotic for the first 12 weeks then crosses over to have the placebo after a 4-week washout. Vivomixx: 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. Placebo: 4.4 grams of maltose and silicon dioxide per sachet	Placebo, Then Vivomixx This group starts with the placebo for the first 12 weeks then crosses over to have Vivomixx probiotic after a 4-week washout. Vivomixx: 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. Placebo: 4.4 grams of maltose and silicon dioxide per sachet
Overall Study STARTED	35	34
Overall Study Taste Test (1 Week)	35	34
Overall Study Part 1 Treatment (12 Weeks)	34	34
Overall Study Washout (4 Weeks)	34	32
Overall Study Part 2 Treatment (12 Weeks)	34	32
Overall Study COMPLETED	31	27
Overall Study NOT COMPLETED	4	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Vivomixx, Then Placebo This group starts with Vivomixx probiotic for the first 12 weeks then crosses over to have the placebo after a 4-week washout. Vivomixx: 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. Placebo: 4.4 grams of maltose and silicon dioxide per sachet	Placebo, Then Vivomixx This group starts with the placebo for the first 12 weeks then crosses over to have Vivomixx probiotic after a 4-week washout. Vivomixx: 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. Placebo: 4.4 grams of maltose and silicon dioxide per sachet
Overall Study Lost to Follow-up	1	3
Overall Study Withdrawal by Subject	2	3
Overall Study Protocol Violation	1	1

Baseline Characteristics

Efficacy of Vivomixx on Behaviour and Gut Function in Autism Spectrum Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Vivomixx, Then Placebo n=35 Participants This group starts with Vivomixx probiotic for the first 12 weeks then crosses over to have the placebo after a 4-week washout. Vivomixx: 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. Placebo: 4.4 grams of maltose and silicon dioxide per sachet	Placebo, Then Vivomixx n=34 Participants This group starts with the placebo for the first 12 weeks then crosses over to have Vivomixx probiotic after a 4-week washout. Vivomixx: 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. Placebo: 4.4 grams of maltose and silicon dioxide per sachet	Total n=69 Participants Total of all reporting groups
Age, Continuous Mean age	8.3 years STANDARD_DEVIATION 2.3 • n=99 Participants	7.3 years STANDARD_DEVIATION 2.9 • n=107 Participants	7.8 years STANDARD_DEVIATION 2.6 • n=206 Participants
Sex: Female, Male Female	4 Participants n=99 Participants	8 Participants n=107 Participants	12 Participants n=206 Participants
Sex: Female, Male Male	31 Participants n=99 Participants	26 Participants n=107 Participants	57 Participants n=206 Participants
Race/Ethnicity, Customized Ethnic origin · Arab	1 Participants n=99 Participants	1 Participants n=107 Participants	2 Participants n=206 Participants
Race/Ethnicity, Customized Ethnic origin · Asian/Asian British	3 Participants n=99 Participants	3 Participants n=107 Participants	6 Participants n=206 Participants
Race/Ethnicity, Customized Ethnic origin · Black/African/Caribbean/Black British	2 Participants n=99 Participants	2 Participants n=107 Participants	4 Participants n=206 Participants
Race/Ethnicity, Customized Ethnic origin · Chinese	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants
Race/Ethnicity, Customized Ethnic origin · Hispanic	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants
Race/Ethnicity, Customized Ethnic origin · Mixed/Multiple ethnic	8 Participants n=99 Participants	4 Participants n=107 Participants	12 Participants n=206 Participants
Race/Ethnicity, Customized Ethnic origin · White	21 Participants n=99 Participants	22 Participants n=107 Participants	43 Participants n=206 Participants
Autism Treatment Evaluation Checklist Total score	70.15 score on a scale STANDARD_DEVIATION 25.28 • n=99 Participants	76.32 score on a scale STANDARD_DEVIATION 30.18 • n=107 Participants	73.24 score on a scale STANDARD_DEVIATION 27.80 • n=206 Participants

PRIMARY outcome

Timeframe: ATEC will be measured at the time of enrolment to the study, after the first 12-week treatment and after the second 12-week treatment by the child's primary carer and also by the child's educator.

Population: All participants who received at least one dose of each intervention and whose primary carer at least completed the ATEC questionnaire at enrolment and after Part 1 treatment. Those who were withdrawn or lost-to-followup in Part 2 (n=6) were assumed to have no change from their last ATEC score.

Outcome measures

Outcome measures
Measure	Vivomixx n=64 Participants Participants who received Vivomixx at an age-group determined dose.	Placebo n=64 Participants Participants who received Placebo powder at an age-group determined dose
A Change in the Autism Treatment Evaluation Checklist (ATEC) Total Score Compared to Baseline.	-12.122 percentage change from baseline score Standard Deviation 20.9140	-11.427 percentage change from baseline score Standard Deviation 20.3055

SECONDARY outcome

Timeframe: GIH will be measured at the time of enrolment to the study, after the first 12-week treatment and after the second 12-week treatment.

Population: All participants who received at least one dose of each intervention and whose primary carer completed at least a GIH at enrolment and after Part 1 treatment. Those who were withdrawn or lost-to-followup in Part 2 (n=6) were assumed to have no change since their last GIH was completed.

In 2003 the Childhood Autism Risks from Genetics and the Environment (CHARGE) study developed and began using a frequency assessment of GI symptoms in autistic children, which they called the Gastrointestinal History Questionnaire. The Gastrointestinal History questionnaire (GIH) includes 10 Likert scale items for the following symptoms: abdominal pain, gaseousness/bloating sensation, diarrhoea, constipation, pain on stooling, vomiting, difficulty swallowing, blood in stools and blood in vomit. These have been equated to a numerical score as follows; never=0, rarely=1, sometimes=2, frequently=3, always=4.

Outcome measures

Outcome measures
Measure	Vivomixx n=66 Participants Participants who received Vivomixx at an age-group determined dose.	Placebo n=66 Participants Participants who received Placebo powder at an age-group determined dose
The Change in the Frequency of Gastrointestinal Symptoms Compared to Baseline, as Measured by the Gastrointestinal History (GIH) Questionnaire. Change in abdominal pain frequency	-0.92 units on a scale Standard Error 0.128	-0.82 units on a scale Standard Error 0.128
The Change in the Frequency of Gastrointestinal Symptoms Compared to Baseline, as Measured by the Gastrointestinal History (GIH) Questionnaire. Change in gaseousness frequency	-0.70 units on a scale Standard Error 0.159	-0.86 units on a scale Standard Error 0.157
The Change in the Frequency of Gastrointestinal Symptoms Compared to Baseline, as Measured by the Gastrointestinal History (GIH) Questionnaire. Change in diarrhoea frequency	-0.92 units on a scale Standard Error 0.149	-0.80 units on a scale Standard Error 0.153
The Change in the Frequency of Gastrointestinal Symptoms Compared to Baseline, as Measured by the Gastrointestinal History (GIH) Questionnaire. Change in constipation frequency	-0.92 units on a scale Standard Error 0.176	-1.00 units on a scale Standard Error 0.153
The Change in the Frequency of Gastrointestinal Symptoms Compared to Baseline, as Measured by the Gastrointestinal History (GIH) Questionnaire. Change in pain on stooling frequency	-0.92 units on a scale Standard Error 0.158	-0.82 units on a scale Standard Error 0.160
The Change in the Frequency of Gastrointestinal Symptoms Compared to Baseline, as Measured by the Gastrointestinal History (GIH) Questionnaire. Change in difficulty swallowing frequency	-0.12 units on a scale Standard Error 0.063	-0.08 units on a scale Standard Error 0.084
The Change in the Frequency of Gastrointestinal Symptoms Compared to Baseline, as Measured by the Gastrointestinal History (GIH) Questionnaire. Change in vomiting frequency	-0.27 units on a scale Standard Error 0.095	-0.23 units on a scale Standard Error 0.094
The Change in the Frequency of Gastrointestinal Symptoms Compared to Baseline, as Measured by the Gastrointestinal History (GIH) Questionnaire. Change in blood in stool frequency	-0.06 units on a scale Standard Error 0.048	-0.06 units on a scale Standard Error 0.043
The Change in the Frequency of Gastrointestinal Symptoms Compared to Baseline, as Measured by the Gastrointestinal History (GIH) Questionnaire. Change in blood in vomit frequency	-0.02 units on a scale Standard Error 0.015	-0.02 units on a scale Standard Error 0.015

SECONDARY outcome

Timeframe: ABC was measured at the time of enrolment to the study, after the first 12-week treatment and after the second 12-week treatment by the child's primary carer.

Population: All participants who received at least one dose of each intervention and whose primary carer at least completed the ABC questionnaire at enrolment and after the Part 1 treatment. Those who were withdrawn or lost-to-follow-up in Part 2 were assumed to have no change from their last ABC questionnaire.

Maladaptive behavior will be measured using five subscales of the ABC: Irritability (15 items), Lethargy/social withdrawal (16 items), Stereotypic behaviour (7 items), Hyperactivity/Noncompliance (16 items) and Inappropriate speech (4 items). A higher score indicates greater difficulty. The minimum score for each section is 0. The maximum scores for the sections are: Irritability 45, Lethargy/social withdrawal 48, Stereotypic behaviour 21, Hyperactivity/Noncompliance 48 and Inappropriate speech 12.

Outcome measures

Outcome measures
Measure	Vivomixx n=62 Participants Participants who received Vivomixx at an age-group determined dose.	Placebo n=62 Participants Participants who received Placebo powder at an age-group determined dose
A Change in the Aberrant Behaviour Checklist (ABC) Section Scores Compared to Baseline. Change in Irritability	-3.00 score on a scale Standard Error 1.100	-3.05 score on a scale Standard Error 1.065
A Change in the Aberrant Behaviour Checklist (ABC) Section Scores Compared to Baseline. Change in Lethargy/social withdrawal	-2.26 score on a scale Standard Error 0.842	-3.11 score on a scale Standard Error .780
A Change in the Aberrant Behaviour Checklist (ABC) Section Scores Compared to Baseline. Change in stereotypic behaviour	-1.06 score on a scale Standard Error 0.404	-1.08 score on a scale Standard Error 0.399
A Change in the Aberrant Behaviour Checklist (ABC) Section Scores Compared to Baseline. Change in Hyperactivity/Noncompliance	-2.42 score on a scale Standard Error 0.944	-2.16 score on a scale Standard Error 0.894
A Change in the Aberrant Behaviour Checklist (ABC) Section Scores Compared to Baseline. Change in Inappropriate speech	-0.45 score on a scale Standard Error 0.290	-0.37 score on a scale Standard Error 0.316

SECONDARY outcome

Timeframe: APSI will be measured at the time of enrolment to the study, after the first 12-week treatment and after the second 12-week treatment.

Population: All participants who received at least one dose of each intervention and whose primary carer at least completed the APSI at enrolment and after Part 1 treatment. Those who were withdrawn or lost-to-followup in Part 2 were assumed to have no change since their last APSI was completed.

This one-page, self-assessment questionnaire was developed and validated in 2012. It is designed to assess parent stress in 13 aspects of autism of concern to parents and to provide a measure of parenting stress specific to core symptoms of autism and common co-occurring issues. It reflects the time, effort and actual difficulty of parenting in the light of the physical, social and communication barriers imposed by autism. It is intended for use by clinicians to assess the effects of an intervention on parenting stress. A higher score indicates greater parenting stress. The minimum score is 0 and the maximum score is 65.

Outcome measures

Outcome measures
Measure	Vivomixx n=64 Participants Participants who received Vivomixx at an age-group determined dose.	Placebo n=64 Participants Participants who received Placebo powder at an age-group determined dose
The Change in the Autism Parenting Stress Index (APSI) Score Compared to Baseline.	-3.73 difference in score on a scale from base Standard Error 0.928	-3.11 difference in score on a scale from base Standard Error 0.872

Adverse Events

Vivomixx

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Vivomixx n=66 participants at risk Participants who received Vivomixx at an age-group determined dose.	Placebo n=68 participants at risk Participants who received Placebo powder at an age-group determined dose
Gastrointestinal disorders Constipation	1.5% 1/66 • Number of events 1 • 6 months	7.4% 5/68 • Number of events 5 • 6 months
Nervous system disorders Seizure	1.5% 1/66 • Number of events 1 • 6 months	0.00% 0/68 • 6 months
General disorders Worsening behaviour	3.0% 2/66 • Number of events 2 • 6 months	4.4% 3/68 • Number of events 3 • 6 months
General disorders Temporary poor sleep	1.5% 1/66 • Number of events 1 • 6 months	0.00% 0/68 • 6 months
Gastrointestinal disorders Faecal incontinence	3.0% 2/66 • Number of events 2 • 6 months	4.4% 3/68 • Number of events 3 • 6 months
Gastrointestinal disorders Loose stools	4.5% 3/66 • Number of events 3 • 6 months	1.5% 1/68 • Number of events 1 • 6 months
Immune system disorders Food intolerance reaction	0.00% 0/66 • 6 months	1.5% 1/68 • Number of events 1 • 6 months
Respiratory, thoracic and mediastinal disorders Persistent cough	0.00% 0/66 • 6 months	1.5% 1/68 • Number of events 1 • 6 months
Psychiatric disorders Panic attack	0.00% 0/66 • 6 months	1.5% 1/68 • Number of events 1 • 6 months
Nervous system disorders Increased sensory sensitivity	0.00% 0/66 • 6 months	1.5% 1/68 • Number of events 1 • 6 months

Additional Information

Susan Simmons

University College London

Phone: +44 7952961881

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place