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Probiotics for Quality of Life in Autism Spectrum Disorders

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02903030
Recruitment Status : Completed
First Posted : September 16, 2016
Results First Posted : February 5, 2020
Last Update Posted : February 5, 2020
Sponsor:
Collaborators:
Autism Treatment Network
Autism Speaks
Information provided by (Responsible Party):
L. Eugene Arnold, Ohio State University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Conditions Autism Spectrum Disorders
Anxiety
Interventions Drug: Maltose (placebo)
Drug: Visbiome Extra Strength
Enrollment 13
Recruitment Details 13 participants were screened and randomized to be in the study at the OSU Wexner Medical Center, Nisonger Center in 2016.
Pre-assignment Details 13 patients were randomized to order, but 3 dropped out because of distance and transportation without providing any follow-up data, leaving 10 who progressed through to study completion. (77% retention rate)
Arm/Group Title Visbiome, Then Placebo Placebo, Then Visbiome
Hide Arm/Group Description

Children aged 3-12 years with ASD, GI symptoms, and anxiety were randomly assigned 1:1 to probiotic Visbiome for 8 weeks, followed by a 3-week washout and an 8 week crossover treatment (19 weeks total).

The probiotic mix (VISBIOME) will be mainly Bifidobacteria and Lactobacilli, in view of the previously reported encouraging clinical studies and safety data.

Visbiome Extra Strength: It is a mix of 8 strains of beneficial bacteria that should improve gut flora, improving GI function and hopefully anxiety

Children aged 3-12 years with ASD, GI symptoms, and anxiety were randomly assigned 1:1 to placebo for 8 weeks, followed by a 3-week washout and an 8 week crossover treatment (19 weeks total).

Placebo matched to probiotic.

Maltose (placebo): Maltose with a trace amount of silicon dioxide

Period Title: First Intervention (8 Weeks)
Started 8 5
Received Intervention 6 4
Completed 6 4
Not Completed 2 1
Reason Not Completed
Withdrawal by Subject             2             1
Period Title: Washout (3 Weeks)
Started 6 4
Completed 6 4
Not Completed 0 0
Period Title: Second Intervention (8 Weeks)
Started 6 4
Completed 6 4
Not Completed 0 0
Arm/Group Title Visbiome, Then Placebo Placebo, the Visbiome Total
Hide Arm/Group Description

Participants were randomly assigned 1:1 to Visbiome probiotic for 8 weeks, followed by a 3-week washout and an 8 week crossover treatment. (19 weeks total) Starting dose: the first 4 weeks, was a half packet twice daily mixed with food. At 4 week and 15-week visit, there was an option to increase to a full packet twice daily if no effect was noted.

The probiotic mix (VISBIOME) will be mainly Bifidobacteria and Lactobacilli, in view of the previously reported encouraging clinical studies and safety data.

Visbiome Extra Strength: It is a mix of 8 strains of beneficial bacteria that should improve gut flora, improving GI function and hopefully anxiety

Particiapants were randomly assigned 1:1 to placebo for 8 weeks, followed by a 3-week washout and an 8 week crossover treatment. (19 weeks total) Starting dose: the first 4 weeks of the probiotic treatment was a half packet twice daily mixed with food. At 4 week and 15-week visit, there was an option to increase to a full packet twice daily if no effect was noted.

Placebo matched to probiotic.

Maltose (placebo): Maltose with a trace amount of silicon dioxide

Total of all reporting groups
Overall Number of Baseline Participants 6 4 10
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 4 participants 10 participants
<=18 years
6
 100.0%
4
 100.0%
10
 100.0%
Between 18 and 65 years
0
   0.0%
0
   0.0%
0
   0.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 4 participants 10 participants
Female
1
  16.7%
3
  75.0%
4
  40.0%
Male
5
  83.3%
1
  25.0%
6
  60.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 4 participants 10 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
2
  33.3%
3
  75.0%
5
  50.0%
White
2
  33.3%
1
  25.0%
3
  30.0%
More than one race
2
  33.3%
0
   0.0%
2
  20.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 6 participants 4 participants 10 participants
6 4 10
Gastrointestinal Module of the Pediatric Quality of Life Inventory (PedsQL)   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 6 participants 4 participants 10 participants
66.73  (20.193) 59.60  (17.214) 63.17  (18.76)
[1]
Measure Description: A 74-item survey with 14 scales. Report forms for specific age ranges assess the parent's perception of the child's GI function and/or symptoms during the last month on a 5-point scale from 0 (never a problem) to 4 (almost always a problem). Items are reverse-scored and transformed to a 0-100 scale so lower scores reflect worse GI dysfunction. Response choices are in Likert-scale format ranging from 0 to 4 (0=Never, 1=Almost Never, 2=Sometimes, 3=Often, 4=Almost Always).
Parent-Rated Anxiety Scale for ASD (PRAS-ASD)   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 6 participants 4 participants 10 participants
40.00  (15.582) 41.25  (10.012) 40.63  (18.52)
[1]
Measure Description: A 25-item single-factor scale measure of emotional stability/anxiety summed to get a score. Higher scores are worse for PRAS-ASD subscale. Scores range from 0-75.
Aberrant Behavior Checklist (ABC)   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 6 participants 4 participants 10 participants
(1) irritability 18.50  (12.661) 25.00  (10.801) 21.75  (16.64)
(2) lethargy 18.83  (12.336) 21.25  (13.598) 20.04  (18.35)
(3) stereotypy 9.33  (4.803) 10.00  (8.287) 9.67  (9.57)
(4) hyperactivity 22.67  (11.639) 35.00  (10.132) 28.83  (15.43)
inappropriate speech 5.33  (3.327) 8.25  (4.500) 6.79  (5.60)
[1]
Measure Description:

The ABC is a 58-item parent rating on a 0-3 scale with five subscales:

  1. . Irritability (includes agitation, aggression, and self-injury, 15 items) with range of scores from 0-45
  2. . Social Withdrawal (16 items) with range of scores from 0-48
  3. . Stereotypies (7 items) with range of scores from 0-21
  4. . Hyperactivity (16 items) with range of scores from 0-48
  5. . Inappropriate Speech (4 items) with range of scores from 0-12.

Higher scores are worse for the ABC subscale.

Social Responsiveness Scale (SRS)   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 6 participants 4 participants 10 participants
82.17  (7.859) 87.00  (4.761) 84.585  (9.189)
[1]
Measure Description: This 65-item rating scale measures the severity of autism spectrum symptoms as they occur in natural social settings. The SRS provides a clear picture of a child's social impairments, assessing social awareness, social information processing, capacity for reciprocal social communication, social anxiety/avoidance, and autistic preoccupations and traits. It is appropriate for use with children from 4 to 18 years of age and will detect changes in core ASD symptoms. A higher score in this scale represents worse symptoms with raw scores summed and generated t-scores ranging from 0-110.
Abbreviated Children's Sleep Habits Questionnaire (CSHQ)   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 6 participants 4 participants 10 participants
43.50  (8.02) 59.75  (13.00) 51.63  (15.27)
[1]
Measure Description: It includes 33 items rated retrospectively over the previous week by parents yielding a total score and eight subscales. Eight subscales include: (1) bedtime resistance (2) sleep onset latency, (3) sleep duration, (4) anxiety around sleep, (5) night awakenings, (6) sleep disordered breathing, (7) parasomnias and (8) morning waking/daytime sleepiness.Total score (summed) range of 0-99. A higher score is a better outcome for this measure.
Parenting Stress Index Short Form (PSI)   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 6 participants 4 participants 10 participants
108.17  (20.731) 129.50  (17.767) 118.84  (27.303)
[1]
Measure Description: The PSI is used to evaluate the degree of stress in the parent-child relationship. The Short Form has 36 items from the full length PSI, rated on a 5-point scale from 1 = strongly disagree, to 5 = strongly agree. It is completed in 10-15 minutes. The PSI may be used for parents of children up to 12 years. It yields a Total Score and three domain scores. This will detect effect on parental stress and QOL. Higher scores are worse for the PSI with sums ranging from 0-180.
1.Primary Outcome
Title Change in Gastrointestinal (GI) Module of the Pediatric Quality of Life Inventory (PedsQL) at From Baseline at Week 8
Hide Description A 74-item survey with 14 scales. Report forms for specific age ranges assess the parent's perception of the child's GI function and/or symptoms during the last month on a 5-point scale from 0 (never a problem) to 4 (almost always a problem). Items are reverse-scored and transformed to a 0-100 scale so lower scores reflect worse GI dysfunction. Response choices are in Likert-scale format ranging from 0 to 4 (0=Never, 1=Almost Never, 2=Sometimes, 3=Often, 4=Almost Always).
Time Frame Baseline and Week 8 of Both the First and Second Intervention
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Visbiome Placebo
Hide Arm/Group Description:

Randomly assigned 1:1 probiotic for 8 weeks, followed by a 3-week washout and an 8 week crossover treatment. (19 weeks total) Starting dose, the first 4 weeks, was a half packet twice daily mixed with food. At 4 week and 15-week visit, there was an option to increase to a full packet twice daily if no effect was noted.

The probiotic mix (VISBIOME) will be mainly Bifidobacteria and Lactobacilli, in view of the previously reported encouraging clinical studies and safety data.

Visbiome Extra Strength: It is a mix of 8 strains of beneficial bacteria that should improve gut flora, improving GI function and hopefully anxiety

Randomly assigned 1:1 placebo for 8 weeks, followed by a 3-week washout and an 8 week crossover treatment. (19 weeks total) Starting dose, the first 4 weeks, was a half packet twice daily mixed with food. At 4 week and 15-week visit, there was an option to increase to a full packet twice daily if no effect was noted.

Placebo matched to probiotic.

Maltose (placebo): Maltose with a trace amount of silicon dioxide

Overall Number of Participants Analyzed 10 10
Mean (Standard Deviation)
Unit of Measure: Units on a scale
17.97  (14.105) 7.98  (11.247)
2.Secondary Outcome
Title Change in Target Symptom Rating From Baseline at Week 8
Hide Description Parents are asked to name the 2 problems of most concern to them at baseline; a clinician helps the parent quantify and describe the problem (frequency, duration, severity, interference with daily life) at baseline. At subsequent visits the clinician reminds the parent of the previous description and helps them again quantify/describe the current state. A panel of blind clinicians reviews the descriptions and rates each on a 9-point scale relative to baseline, from remission (0) to disastrously worse (9), with 5=no change. These ratings are averaged, capturing the issues of most concern to parents across families. For purposes of this study, one of the 2 problems will be required to pertain to GI function, and will be analyzed separately as well as being averaged into the overall symptom rating.
Time Frame Baseline and Week 8 of Both the First and Second Intervention
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Visbiome Placebo
Hide Arm/Group Description:

The probiotic mix (VISBIOME) will be mainly Bifidobacteria and Lactobacilli, in view of the previously reported encouraging clinical studies and safety data.

Visbiome Extra Strength: It is a mix of 8 strains of beneficial bacteria that should improve gut flora, improving GI function and hopefully anxiety

Placebo matched to probiotic.

Maltose (placebo): Maltose with a trace amount of silicon dioxide

Overall Number of Participants Analyzed 10 10
Mean (Standard Deviation)
Unit of Measure: Units on a scale
-2.10  (1.647) -0.60  (1.370)
3.Secondary Outcome
Title Change in Parent Anxiety Checklist--ASD From Baseline at Week 8
Hide Description A 25-item single-factor scale measure of emotional stability/anxiety. Higher scores are worse for PRAS-ASD subscale, hence a negative estimate means more improvement with the probiotics compared to control. Scores range from 0-75.
Time Frame Baseline and Week 8 of Both the First and Second Intervention
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Visbiome Placebo
Hide Arm/Group Description:

The probiotic mix (VISBIOME) will be mainly Bifidobacteria and Lactobacilli, in view of the previously reported encouraging clinical studies and safety data.

Visbiome Extra Strength: It is a mix of 8 strains of beneficial bacteria that should improve gut flora, improving GI function and hopefully anxiety

Placebo matched to probiotic. Maltose (placebo): Maltose with a trace amount of silicon dioxide
Overall Number of Participants Analyzed 10 10
Mean (Standard Deviation)
Unit of Measure: Units on a scale
-6.20  (10.830) -4.10  (11.259)
4.Secondary Outcome
Title Change in The Aberrant Behavior Checklist (ABC) From Baseline at Week 8
Hide Description

The ABC is a 58-item parent rating on a 0-3 scale with five subscales:

  • Irritability (includes agitation, aggression, and self-injury, 15 items) with range of scores from 0-45
  • Social Withdrawal (16 items) with range of scores from 0-48
  • Stereotypies (7 items) with range of scores from 0-21
  • Hyperactivity (16 items) with range of scores from 0-48
  • Inappropriate Speech (4 items) with range of scores from 0-12.

Higher scores are worse for the ABC subscale, hence a negative estimate means more improvement with the probiotics compared to control.

Time Frame Baseline and Week 8 of Both the First and Second Intervention
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Visbiome Placebo
Hide Arm/Group Description:

The probiotic mix (VISBIOME) will be mainly Bifidobacteria and Lactobacilli, in view of the previously reported encouraging clinical studies and safety data.

Visbiome Extra Strength: It is a mix of 8 strains of beneficial bacteria that should improve gut flora, improving GI function and hopefully anxiety

Placebo matched to probiotic. Maltose (placebo): Maltose with a trace amount of silicon dioxide
Overall Number of Participants Analyzed 10 10
Mean (Standard Deviation)
Unit of Measure: Units on a scale
ABC (1) Irritability -1.80  (5.245) -3.50  (5.622)
ABC (2) Lethargy -2.60  (8.140) -2.50  (4.327)
ABC (3) Stereotypy -1.20  (4.367) -1.80  (3.521)
ABC (4) Hyperactivity -2.10  (6.385) -5.40  (6.851)
ABC (5) Inappropriate Speech -0.40  (2.011) -0.10  (1.370)
5.Secondary Outcome
Title Change in Social Responsiveness Scale (SRS) From Baseline at Week 8
Hide Description This 65-item rating scale measures the severity of autism spectrum symptoms as they occur in natural social settings. The SRS provides a clear picture of a child's social impairments, assessing social awareness, social information processing, capacity for reciprocal social communication, social anxiety/avoidance, and autistic preoccupations and traits. It is appropriate for use with children from 4 to 18 years of age and will detect changes in core ASD symptoms. A higher score in this scale represents worse symptoms with raw scores summed and generated t-scores ranging from 0-110.
Time Frame Baseline and Week 8 of Both the First and Second Intervention
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Visbiome Placebo
Hide Arm/Group Description:

The probiotic mix (VISBIOME) will be mainly Bifidobacteria and Lactobacilli, in view of the previously reported encouraging clinical studies and safety data.

Visbiome Extra Strength: It is a mix of 8 strains of beneficial bacteria that should improve gut flora, improving GI function and hopefully anxiety

Placebo matched to probiotic. Maltose (placebo): Maltose with a trace amount of silicon dioxide
Overall Number of Participants Analyzed 10 10
Mean (Standard Deviation)
Unit of Measure: Units on a scale
-4.70  (6.255) -1.70  (5.187)
6.Secondary Outcome
Title Children's Sleep Habits Questionnaire (CSHQ) at Week 8
Hide Description It includes 33 items rated retrospectively over the previous week by parents yielding a total score and eight subscales. Eight subscales include: (1) bedtime resistance (2) sleep onset latency, (3) sleep duration, (4) anxiety around sleep, (5) night awakenings, (6) sleep disordered breathing, (7) parasomnias and (8) morning waking/daytime sleepiness.Total score (summed) range of 0-99. A higher score is a better outcome for this measure.
Time Frame Week 8 of Both the First and Second Intervention
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Visbiome Placebo
Hide Arm/Group Description:

The probiotic mix (VISBIOME) will be mainly Bifidobacteria and Lactobacilli, in view of the previously reported encouraging clinical studies and safety data.

Visbiome Extra Strength: It is a mix of 8 strains of beneficial bacteria that should improve gut flora, improving GI function and hopefully anxiety

Placebo matched to probiotic.

Maltose (placebo): Maltose with a trace amount of silicon dioxide

Overall Number of Participants Analyzed 10 10
Mean (Standard Deviation)
Unit of Measure: Units on a scale
42.80  (7.510) 43.44  (7.502)
7.Secondary Outcome
Title Change in The Parenting Stress Index Short Form (PSI)
Hide Description The PSI is used to evaluate the degree of stress in the parent-child relationship. The Short Form has 36 items from the full length PSI, rated on a 5-point scale from 1 = strongly disagree, to 5 = strongly agree. It is completed in 10-15 minutes. The PSI may be used for parents of children up to 12 years. It yields a Total Score and three domain scores. This will detect effect on parental stress and QOL. Higher scores (ranging from 0-180) are worse for PSI, hence a negative estimate means more improvement with the probiotics compared to control.
Time Frame Baseline and Week 8 of Both the First and Second Intervention
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Visbiome Placebo
Hide Arm/Group Description:

The probiotic mix (VISBIOME) will be mainly Bifidobacteria and Lactobacilli, in view of the previously reported encouraging clinical studies and safety data.

Visbiome Extra Strength: It is a mix of 8 strains of beneficial bacteria that should improve gut flora, improving GI function and hopefully anxiety

Placebo matched to probiotic. Maltose (placebo): Maltose with a trace amount of silicon dioxide
Overall Number of Participants Analyzed 10 10
Mean (Standard Deviation)
Unit of Measure: Units on a scale
-9.60  (16.675) -1.70  (5.187)
Time Frame After Baseline: 4 weeks, 8 weeks, 15 weeks, 19 weeks
Adverse Event Reporting Description Collected AE data from all participants of the study.
 
Arm/Group Title Visbiome Placebo
Hide Arm/Group Description

Randomly assigned 1:1 probiotic for 8 weeks, followed by a 3-week washout and an 8 week crossover treatment. (19 weeks total) Starting dose, the first 4 weeks, was a half packet twice daily mixed with food. At 4 week and 15-week visit, there was an option to increase to a full packet twice daily if no effect was noted.

The probiotic mix (VISBIOME) will be mainly Bifidobacteria and Lactobacilli, in view of the previously reported encouraging clinical studies and safety data.

Visbiome Extra Strength: A mix of 8 strains of beneficial bacteria that should improve gut flora, improving GI function and hopefully anxiety

Randomly assigned 1:1 placebo for 8 weeks, followed by a 3-week washout and an 8 week crossover treatment. (19 weeks total) Starting dose, the first 4 weeks, was a half packet twice daily mixed with food. At 4 week and 15-week visit, there was an option to increase to a full packet twice daily if no effect was noted.

Placebo matched to probiotic.

Maltose (placebo): Maltose with a trace amount of silicon dioxide

All-Cause Mortality
Visbiome Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/10 (0.00%)      0/10 (0.00%)    
Hide Serious Adverse Events
Visbiome Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/10 (0.00%)      0/10 (0.00%)    
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Visbiome Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/10 (60.00%)      4/10 (40.00%)    
Gastrointestinal disorders     
Gastrointestinal Disorders  1 [1]  6/10 (60.00%)  7 4/10 (40.00%)  9
1
Term from vocabulary, MedDRA (Unspecified)
Indicates events were collected by systematic assessment
[1]
Abdominal distension (S:1, P:1)** Abdominal pain (S:1 P:2) Diarrhoea (S:0 P:2) Flatulence (S:3 P:2) Nausea (S:1 P:2) Vomiting (S:1 P:0) ** S= Supplement/Probiotic P = Placebo number is events reported
Small sample. Crossover did not accurately anticipate the duration of carryover Crossover not the best design for this treatment.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. L. Eugene Arnold, MD, MED. Professor Emeritus College of Medicine
Organization: Nisonger Center
Phone: 614-685-6701
EMail: l.arnold@osumc.edu
Layout table for additonal information
Responsible Party: L. Eugene Arnold, Ohio State University
ClinicalTrials.gov Identifier: NCT02903030    
Other Study ID Numbers: 2016H0174
First Submitted: June 14, 2016
First Posted: September 16, 2016
Results First Submitted: October 10, 2019
Results First Posted: February 5, 2020
Last Update Posted: February 5, 2020