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Probiotics for Quality of Life in Autism Spectrum Disorders

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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

Tracking Information
First Submitted Date  ICMJE June 14, 2016
First Posted Date  ICMJE September 16, 2016
Results First Submitted Date  ICMJE October 10, 2019
Results First Posted Date  ICMJE February 5, 2020
Last Update Posted Date February 5, 2020
Study Start Date  ICMJE August 2016
Actual Primary Completion Date December 1, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 24, 2020)
Change in Gastrointestinal (GI) Module of the Pediatric Quality of Life Inventory (PedsQL) at From Baseline at Week 8 [ Time Frame: Baseline and Week 8 of Both the First and Second Intervention ]
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).
Original Primary Outcome Measures  ICMJE
 (submitted: September 12, 2016)
Change in Gastrointestinal (GI) Module of the Pediatric Quality of Life Inventory (PedsQL) (Varni et al., 2001; (Varni, Burwinkle, & Seid, 2006; Varni et al, 2014) [ Time Frame: Screen, Baseline, Week 4, Week 8, Week 11, Week 15, Week 19 ]
A 74-item survey with 14 scales (# of items): stomach pain & hurt (6 items), discomfort when eating (5), food & drink limits (6), trouble swallowing (3), heartburn/reflux (4), nausea/vomiting (4), gas & bloating (7), constipation (14), blood in poop (2), diarrhea (7), worry about going poop (5), worry about stomachaches (2), medicines (4), and communication (5). 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).
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 24, 2020)
  • Change in Target Symptom Rating From Baseline at Week 8 [ Time Frame: Baseline and Week 8 of Both the First and Second Intervention ]
    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.
  • Change in Parent Anxiety Checklist--ASD From Baseline at Week 8 [ Time Frame: Baseline and Week 8 of Both the First and Second Intervention ]
    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.
  • Change in The Aberrant Behavior Checklist (ABC) From Baseline at Week 8 [ Time Frame: Baseline and Week 8 of Both the First and Second Intervention ]
    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.
  • Change in Social Responsiveness Scale (SRS) From Baseline at Week 8 [ Time Frame: Baseline and Week 8 of Both the First and Second Intervention ]
    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.
  • Children's Sleep Habits Questionnaire (CSHQ) at Week 8 [ Time Frame: Week 8 of Both the First and Second Intervention ]
    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.
  • Change in The Parenting Stress Index Short Form (PSI) [ Time Frame: Baseline and Week 8 of Both the First and Second Intervention ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 12, 2016)
  • Change in Target Symptom Rating (Arnold et al, 2003) [ Time Frame: Baseline, Week 4, Week 8, Week 11, Week 15, Week 19 ]
    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 to disastrously worse, 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.
  • Change in Parent Anxiety Checklist--ASD (Scahill, Lecavalier, Bears, & Aman, 2015) [ Time Frame: Screen, Baseline, Week 4, Week 8, Week 11, Week 15, Week 19 ]
  • Change in The Aberrant Behavior Checklist (ABC) (Aman et al., 1985a, 1985b) [ Time Frame: Baseline, Week 4, Week 8, Week 11, Week 15, Week 19 ]
    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); 2) Social Withdrawal (16 items); 3) Stereotypies (7 items); 4) Hyperactivity (16 items); and 5) Inappropriate Speech (4 items).
  • Change in Social Responsiveness Scale (SRS) (Costantino et al., 2003) [ Time Frame: Baseline, Week 8, Week 11, Week 19 ]
    This 65-item rating scale measures the severity of autism spectrum symptoms as they occur in natural social settings. Completed by a parent or teacher in 15 to 20 minutes, 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.
  • Change in Children's Sleep Habits Questionnaire (CSHQ) (Owens, Spirito, & Mcguinn, 2000) [ Time Frame: Baseline, Week 8, Week 11, Week 19 ]
    It includes 33 items rated retrospectively over the previous week by parents. 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. In a recent study of the Autism Treatment Network, 75% of the participants analyzed had a CSHQ score >41, the clinical threshold for sleep problems (Hollway, Aman, and Butter, 2013). Sleep greatly affects quality of life for both children and parents, and it is important to detect any changes in this important vegetative function.
  • Change in The Parenting Stress Index Short Form (PSI) (Abidin,1995) [ Time Frame: Baseline, Week 8 ]
    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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: September 12, 2016)
Change in Vital signs [ Time Frame: Screen, Baseline, Week 4, Week 8, Week 11, Week 15, Week 19 ]
 
Descriptive Information
Brief Title  ICMJE Probiotics for Quality of Life in Autism Spectrum Disorders
Official Title  ICMJE Probiotics for Quality of Life in Autism Spectrum Disorders
Brief Summary A randomized pilot trial of a probiotic for quality of life in autism spectrum disorder (ASD), targeting gastrointestinal (GI) symptoms.
Detailed Description The physical and mental/emotional health of people with autism spectrum disorder (ASD) are closely connected. The emerging data on immune abnormalities and gut microbiome differences, and interactions of the genome with these suggest a possible etiological link between physical and mental dysfunction, especially the gastrointestinal (GI) dysfunction and severe anxiety that many individuals with ASD manifest. The investigators have preliminary clinical evidence that children with ASD & GI symptoms differ in microbiome composition and function from neurotypical children with GI symptoms. The investigators hypothesize that altered host-microbial signals, which include altered fecal neurotransmitter gamma-aminobutyric acid (GABA) levels contribute towards anxiety and sensory over-responsivity in ASD. Our preliminary findings also show that probiotic Visbiome Extra Strength, improves GI and pain symptoms, correlating with altered gut microbiome composition and related metabolites (the macrobiome). The proposed crossover trial will explore the possibilities of this new appreciation of the microbiome-mental/physical function connection for ASD, GI dysfunction, and anxiety. If altering the gut microbiome results in better GI and emotional function, it could improve the quality of life for children with ASD and their parents. A pilot trial with 12 children with ASD will test feasibility for a proposed three-site crossover randomized clinical trial (RCT) of probiotics (beneficial bacteria including Lactobacilli & Bifidobacteria) in 60 children 3-12 years old with ASD, GI dysfunction, & anxiety. In a balanced crossover children will be randomized 1;1 to Visbiome or placebo first, 8 weeks per condition with 3 weeks washout between. The investigators have access to significant fecal microbiome and metabolome data from NIH-funded Human Microbiome Projects (HMP) on similar-age healthy and irritable-bowel children, with and without ASD. These will help leverage our understanding of macrobiome changes that correlate with functional improvement of GI and abdominal pain symptoms. Pilot study efficiency will also benefit from those HMPs having already collected and analyzed baseline stools for some children with ASD, thus saving significant costs for baseline stool analyses for the pilot.
Study Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Autism Spectrum Disorders
  • Anxiety
Intervention  ICMJE
  • Drug: Maltose (placebo)
    Maltose with a trace amount of silicon dioxide
    Other Name: Maltose with silicon dioxide
  • Drug: Visbiome Extra Strength
    It is a mix of 8 strains of beneficial bacteria that should improve gut flora, improving GI function and hopefully anxiety
Study Arms  ICMJE
  • Experimental: Visbiome, Then Placebo
    The probiotic mix (VISBIOME) will be mainly Bifidobacteria and Lactobacilli, in view of the previously reported encouraging clinical studies and safety data.
    Intervention: Drug: Visbiome Extra Strength
  • Placebo Comparator: Placebo, Then Visbiome
    Placebo matched to probiotic.
    Intervention: Drug: Maltose (placebo)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 24, 2020)
13
Original Estimated Enrollment  ICMJE
 (submitted: September 12, 2016)
12
Actual Study Completion Date  ICMJE December 1, 2017
Actual Primary Completion Date December 1, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. have DSM-5 ASD on clinical evaluation by a doctoral-level diagnostician, confirmed by Autism Diagnostic Interview-Revised or Autism Diagnostic Observation Schedule;
  2. be between 3 and 12 years old;
  3. have >2 mo. abdominal pain, constipation, diarrhea, and/or vomiting, with an item-mean score >2 on at least one scale of the GI module of the PedsQL scale;
  4. have clinical anxiety symptoms with an item mean of >1.0 (0-3 scale) on the new Autism Anxiety Scale.

Participants will be recruited from minority, poor, inner city, or rural populations.

Exclusion Criteria:

  1. Antibiotics in 2 months prior to enrolling;
  2. Prior bowel surgery;
  3. Chronic serious medical condition (e.g., diabetes);
  4. Weight or height < 3rd %ile for age;
  5. Chronic anti-inflammatory use within 2 months prior to enrolling;
  6. History of inflammatory bowel disease, Celiac disease, or eosinophilic disorders (e.g., eosinophilic esophagitis);
  7. Already taking probiotics within the previous 6 months.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 3 Years to 12 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02903030
Other Study ID Numbers  ICMJE 2016H0174
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party L. Eugene Arnold, Ohio State University
Study Sponsor  ICMJE Ohio State University
Collaborators  ICMJE
  • Autism Treatment Network
  • Autism Speaks
Investigators  ICMJE
Principal Investigator: Eugene Arnold, MD Ohio State University
PRS Account Ohio State University
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP