Clinical trial NCT03337035: Probiotics and Oxytocin Nasal Spray on Social Behaviors of Autism Spectrum Disorder (ASD) Children
Official title: The Effects of Probiotics and Oxytocin Nasal Spray on Social Behaviors of ASD Children- A Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Autism Spectrum Disorder
Keywords: Probiotics, Oxytocin
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2017-11-08
Enrollment: 35
Sex: ALL
Minimum age (years): 3
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Phase 1: a. oral placebo, and b. oral probiotics; Phase 2: a. intranasal OXT + oral placebo, and b. intranasal OXT + oral probiotics
Primary purpose: TREATMENT

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.

Detailed description: This study description is in accordance with the Consolidated Standards of Reporting Trials (CONSORT) guidelines that are published for the evaluation of randomized controlled trials. This clinical trial is a randomized, double-blind placebo controlled study. Subjects will be randomized to 2 groups:

Phase 1: a. oral placebo, and b. oral probiotics; Phase 2: a. intranasal Oxytocin(OXT) + oral placebo, and b. intranasal OXT + oral probiotics

The treatment will proceed for a total of 28 weeks. In the first phase (16 weeks), all the patients will be randomly and proportionally divided into two groups: Group A (30 subjects) receives oral probiotics while Group B (30 subjects) receives an oral placebo. In the second phase, subjects in Group A and Group B will continue their respective oral probiotics or placebo administration as in Phase 1. In addition, both groups will be simultaneously administered with intranasal OXT spray.

Testing will be performed 3 times total (before, during, and after treatment). The tests include behavioral surveys, cognitive tests, clinical autonomic tests, and blood tests for oxytocin levels. Investigators plan to select up to 10 subjects from each group to conduct a series of MRI studies at week 0, week 16 and week 28.

Eligibility criteria: Inclusion Criteria:

1. Age between 3-25years old;
2. 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
3. A care provider who can reliably bring the participant to study visits;
4. No planned changes in medications or psychosocial interventions during trial (stable medications within the last 2 weeks);
5. Willingness to provide blood samples

Exclusion Criteria:

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

Primary outcomes:
measure: Social Responsiveness Scale (SRS) Edition 2
timeFrame: change from baseline at 0, 16, and 28 weeks
measure: Aberrant Behavior Checklist (ABC) Edition 2
timeFrame: change from baseline at 0, 16, and 28 weeks
Secondary outcomes:
measure: Neuroinflammation and Oxytocin levels
timeFrame: change from baseline at 0, 16, and 28 weeks
measure: structural MRI
timeFrame: change from baseline at 0, 16, and 28 weeks
measure: Functional MRI (resting state)
timeFrame: change from baseline at 0, 16, and 28 weeks
measure: Functional MRI (task based)
timeFrame: change from baseline at 0, 16, and 28 weeks
measure: Autonomic indices 1
timeFrame: change from baseline at 0, 16, and 28 weeks
measure: Autonomic indices 2
timeFrame: change from baseline at 0, 16, and 28 weeks
measure: Autonomic indices 3
timeFrame: change from baseline at 0, 16, and 28 weeks
measure: Autonomic indices 4
timeFrame: change from baseline at 0, 16, and 28 weeks
measure: Autonomic indices 5
timeFrame: change from baseline at 0, 16, and 28 weeks
measure: Microbiome
timeFrame: change from baseline at 0, 16, and 28 weeks
measure: Eye tracking and Behavioral task (joint attention)
timeFrame: change from baseline at 0, 16, and 28 weeks
measure: Eye tracking and behavioral task (emotion response)
timeFrame: change from baseline at 0, 16, and 28 weeks
measure: Eye tracking and behavioral task (eye behavior)
timeFrame: change from baseline at 0, 16, and 28 weeks
Other outcomes:
Locations:
city: Charlestown
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Xue-Jun Kong, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.