Probiotics and Oxytocin Nasal Spray on Social Behaviors of Autism Spectrum Disorder (ASD) Children

NCT03337035 | Completed Phase 1 FDA Drug

• 1 other identifier: 2017P001667
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

Because oral probiotics reported to potentially induce endogenous Oxytocin, and Oxytocin has been reported to improve social behaviors, the investigators will conduct a pilot trial to compare the effects of probiotics and Oxytocin on social behavioral changes in ASD children. Additionally, the investigators will check oxytocin levels, and perform brain fMRI in some subjects, in order to determine which treatment is more efficient, sustainable, and practical, and whether both treatments in combination are better than either treatment alone. If the trial is conclusive, the investigators will conduct a trial in large scale to understand more the mechanism of ASD behaviors and corresponding effective interventions.

Conditions

Autism Spectrum Disorder

Keywords

Probiotics, Oxytocin

Outcome Measures

Primary Outcomes (2)

• Social Responsiveness Scale (SRS) Edition 2

  social communication and behavior - The scoring is based on T-score which is based on the sum of responses as follows (76 to higher - severe, 66 to 75- moderate deficiencies, 60 to 65 - mild deficiencies, 59 and below is not clinically significant for ASD).

  change from baseline at 0, 16, and 28 weeks

• Aberrant Behavior Checklist (ABC) Edition 2

  social behavior test - The total score is calculated based on 5 sub-scales (Irritability, Social Withdrawal, Stereotypic Behavior, Hyperactive/Noncompliance, and Inappropriate Speech). There are 58 questions that are scored on a 0-3 scale 0 -"not at all a problem", 1- "the behavior is a problem but slight in degree", 2- "the problem is moderately serious" and 3- "the problem is severe in degree". Based on this sub-scores are calculated and added to get the total score.

  change from baseline at 0, 16, and 28 weeks

Secondary Outcomes (13)

• Neuroinflammation and Oxytocin levels

  change from baseline at 0, 16, and 28 weeks

• structural MRI

  change from baseline at 0, 16, and 28 weeks

• Functional MRI (resting state)

  change from baseline at 0, 16, and 28 weeks

• Functional MRI (task based)

  change from baseline at 0, 16, and 28 weeks

• Autonomic indices 1

  change from baseline at 0, 16, and 28 weeks

Study Arms (2)

oral probiotics and oxytocin spray

ACTIVE COMPARATOR

Subjects will receive oral probiotics, 2 pills per day, for 28 weeks. For the last 12 weeks, subjects will also receive intranasal oxytocin spray at the following dose: 4 IU in week 1, 8 IU in week 2, 16 IU in week 3, and 24 IU in weeks 4-12.

Drug: intranasal oxytocin; Dietary Supplement: oral probiotics

oral placebo and oxytocin spray

PLACEBO COMPARATOR

Subjects will receive oral placebo, 2 pills per day, for 28 weeks. For the last 12 weeks, subjects will also receive intranasal oxytocin spray at the following dose: 4 IU in week 1, 8 IU in week 2, 16 IU in week 3, and 24 IU in weeks 4-12.

Drug: intranasal oxytocin; Dietary Supplement: oral placebo

Interventions

intranasal oxytocin DRUG

4-24 IU per day, dosage gradually increases

Also known as: Novartis Syntocinon

oral placebo and oxytocin spray; oral probiotics and oxytocin spray

oral probiotics DIETARY_SUPPLEMENT

200 million cfu per day

oral probiotics and oxytocin spray

oral placebo DIETARY_SUPPLEMENT

2 pills per day

oral placebo and oxytocin spray

Eligibility Criteria

• Age: 3 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age between 3-25years old;
• Pre-existing diagnosis of autism; subjects may be asked to provide documentation confirming diagnosis by DSM-V-TR criteria, ADOS, ADI-R, or other clinical forms
• A care provider who can reliably bring the participant to study visits;
• No planned changes in medications or psychosocial interventions during trial (stable medications within the last 2 weeks);
• Willingness to provide blood samples

You may not qualify if:

• Pregnant woman (before or during the study).
• Comorbidity of other neurological and/or psychiatric disorders such as unstable seizures, schizophrenia, schizoaffective disorder, bipolar disorders or history of substance abuse.
• Psychotropic medication use
• Subjects with active cardiovascular disease that is not controlled by medication.
• Oxytocin, antibiotic, or probiotic use within the last 30 days.
• Regular nasal obstruction or nosebleeds
• Significant hearing, vision, or motor impairments
• Habitual consumption of large volumes of water
• Started taking new medications within the last 2 weeks

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Charlestown, Massachusetts, 02129, United States

Location

Related Publications (2)

• Sherman HT, Liu K, Kwong K, Chan ST, Li AC, Kong XJ. Carbon monoxide (CO) correlates with symptom severity, autoimmunity, and responses to probiotics treatment in a cohort of children with autism spectrum disorder (ASD): a post-hoc analysis of a randomized controlled trial. BMC Psychiatry. 2022 Aug 8;22(1):536. doi: 10.1186/s12888-022-04151-3.

  PMID: 35941573 DERIVED

• Kong XJ, Liu J, Li J, Kwong K, Koh M, Sukijthamapan P, Guo JJ, Sun ZJ, Song Y. Probiotics and oxytocin nasal spray as neuro-social-behavioral interventions for patients with autism spectrum disorders: a pilot randomized controlled trial protocol. Pilot Feasibility Stud. 2020 Feb 12;6:20. doi: 10.1186/s40814-020-0557-8. eCollection 2020.

  PMID: 32082606 DERIVED

MeSH Terms

Conditions

Autism Spectrum Disorder

Interventions

Probiotics

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Dietary Supplements; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Officials

• Xue-Jun Kong, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: this study will be double blinded for both participants/guardians and medication administrator
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Investigator

Model Details: Phase 1: a. oral placebo, and b. oral probiotics; Phase 2: a. intranasal OXT + oral placebo, and b. intranasal OXT + oral probiotics

Study Record Dates

• First Submitted: October 31, 2017
• First Posted: November 8, 2017
• Study Start: December 1, 2018
• Primary Completion: October 2, 2019
• Study Completion: October 2, 2019
• Last Updated: March 4, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)