Autism Spectrum DisorderPhase 1NCT03337035
Probiotics and Oxytocin Nasal Spray on Social Behaviors of Autism Spectrum Disorder (ASD) Children
A Phase 1 study testing intranasal oxytocin and oral probiotics in people with Autism Spectrum Disorder, run by Massachusetts General Hospital at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 3 to 25 years
- Conditions the study is for
- Autism Spectrum Disorder
- What is being tested?
- intranasal oxytocin and oral probiotics
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 35 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Dec 2018to 2 Oct 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 25 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 9Show fewer
- Significant hearing, vision, or motor impairments
- Habitual consumption of large volumes of water
- Started taking new medications within the last 2 weeks
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Charlestown, Massachusetts, 02129
About this study
Official title: The Effects of Probiotics and Oxytocin Nasal Spray on Social Behaviors of ASD Children- A Pilot Study
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.
Read the 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.
- Conditions
- Autism Spectrum Disorder
- Being tested
- intranasal oxytocin, oral probiotics, oral placebo
- Keywords
- Probiotics, Oxytocin
- Medical subject headings
- Autism Spectrum Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
intranasal oxytocinDrug
Also called Novartis Syntocinon
4-24 IU per day, dosage gradually increases
oral probioticsDietary supplement
200 million cfu per day
oral placeboDietary supplement
2 pills per day
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: intranasal oxytocin; Dietary Supplement: oral placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Measured: change from baseline at 0, 16, and 28 weeks
Secondary outcomes (13)
Neuroinflammation and Oxytocin levels
neuroendocrine biomarker measured in blood ( Melatonin, Oxytocin, Tumour Necrosis Factor alpha, testosterone and Interleukin 6)
Measured: change from baseline at 0, 16, and 28 weeks
structural MRI
The software Freesurfer will be used to calculate volume of brain regions and diffusion parameters (e.g. fractional anisotropy and mean diffusivity) from structural T1 and diffusion tensor images respectively. T-tests will be applied for group comparisons.
Measured: change from baseline at 0, 16, and 28 weeks
Functional MRI (resting state)
Correlation analysis will be used to calculate the connectivity across different brain regions. T-tests will be used for group comparisons.
Measured: change from baseline at 0, 16, and 28 weeks
Functional MRI (task based)
General linear modeling will be used to calculate brain responses to the tasks. T-tests will be used for group comparisons.
Measured: change from baseline at 0, 16, and 28 weeks
Autonomic indices 1
Blood volume pulse
Measured: change from baseline at 0, 16, and 28 weeks
Autonomic indices 2
heart rate
Measured: change from baseline at 0, 16, and 28 weeks
Autonomic indices 3
peripheral skin temperature
Measured: change from baseline at 0, 16, and 28 weeks
Autonomic indices 4
skin electrodermal activity
Measured: change from baseline at 0, 16, and 28 weeks
Autonomic indices 5
blood oxygen saturation
Measured: change from baseline at 0, 16, and 28 weeks
Microbiome
16s metagenomic sequencing of the microbiome
Measured: change from baseline at 0, 16, and 28 weeks
Eye tracking and Behavioral task (joint attention)
joint attention - Conduct T-tests and calculate P values for total and average fixation values for each area of interest
Measured: change from baseline at 0, 16, and 28 weeks
Eye tracking and behavioral task (emotion response)
emotion response - The accuracy and reaction time will be calculated for each time point. Then an ANOVA will be used to compare the results.
Measured: change from baseline at 0, 16, and 28 weeks
Eye tracking and behavioral task (eye behavior)
eye behavior - Conduct T-tests and calculate P values for total and average fixation values for each area of interest
Measured: change from baseline at 0, 16, and 28 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2017
- Study start1 Dec 2018
- Primary completion2 Oct 2019
- Study completion2 Oct 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Autism Spectrum DisorderStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Phase 1: a. oral placebo, and b. oral probiotics; Phase 2: a. intranasal OXT + oral placebo, and b. intranasal OXT + oral probiotics
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Xuejun Kong,MD, Massachusetts General Hospital
- Investigators
- Xue-Jun Kong, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03337035
- Sponsor's protocol ID
- 2017P001667
- Status last verified
- Mar 2020
- First submitted
- 31 Oct 2017
- Last updated
- 4 Mar 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: There is no plan to share data with researchers not involved in this study.
Publications
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.
PubMed 35941573Kong 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.
PubMed 32082606
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Probiotics and Oxytocin Nasal Spray on Social Behaviors of ASD Children- A Pilot Study
- ClinicalTrials.gov ID
- NCT03337035
- Acronym / sponsor ID
- 2017P001667
- Conditions
- Autism Spectrum Disorder
- Keywords
- Probiotics, Oxytocin
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Study start
- 1 Dec 2018 (actual)
- Primary completion
- 2 Oct 2019 (actual)
- Study completion
- 2 Oct 2019 (actual)
- First posted
- 8 Nov 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- Phase 1: a. oral placebo, and b. oral probiotics; Phase 2: a. intranasal OXT + oral placebo, and b. intranasal OXT + oral probiotics
| Arm | Type | Receives |
|---|---|---|
| oral probiotics and oxytocin spray | Active comparator | Drug: intranasal oxytocin, Dietary Supplement: oral probioticsSubjects 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. |
| oral placebo and oxytocin spray | Placebo comparator | Drug: intranasal oxytocin, Dietary Supplement: oral placeboSubjects 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. |
Who may qualify
- Ages
- 3 to 25 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| intranasal oxytocinAlso: Novartis Syntocinon4-24 IU per day, dosage gradually increases | Drug | oral placebo and oxytocin spray, oral probiotics and oxytocin spray |
| oral probiotics200 million cfu per day | Dietary supplement | oral probiotics and oxytocin spray |
| oral placebo2 pills per day | Dietary supplement | oral placebo and oxytocin spray |
Primary outcome
Social Responsiveness Scale (SRS) Edition 2
Time frame: change from baseline at 0, 16, and 28 weeks
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).
Aberrant Behavior Checklist (ABC) Edition 2
Time frame: change from baseline at 0, 16, and 28 weeks
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.
13 secondary outcomes
Neuroinflammation and Oxytocin levels
Time frame: change from baseline at 0, 16, and 28 weeks
structural MRI
Time frame: change from baseline at 0, 16, and 28 weeks
Functional MRI (resting state)
Time frame: change from baseline at 0, 16, and 28 weeks
Functional MRI (task based)
Time frame: change from baseline at 0, 16, and 28 weeks
Autonomic indices 1
Time frame: change from baseline at 0, 16, and 28 weeks
Autonomic indices 2
Time frame: change from baseline at 0, 16, and 28 weeks
Autonomic indices 3
Time frame: change from baseline at 0, 16, and 28 weeks
Autonomic indices 4
Time frame: change from baseline at 0, 16, and 28 weeks
Autonomic indices 5
Time frame: change from baseline at 0, 16, and 28 weeks
Microbiome
Time frame: change from baseline at 0, 16, and 28 weeks
Eye tracking and Behavioral task (joint attention)
Time frame: change from baseline at 0, 16, and 28 weeks
Eye tracking and behavioral task (emotion response)
Time frame: change from baseline at 0, 16, and 28 weeks
Eye tracking and behavioral task (eye behavior)
Time frame: change from baseline at 0, 16, and 28 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2020.
- Derived from this study: PubMed 35941573Sherman 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.
- Derived from this study: PubMed 32082606Kong 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.
- Individual participant dataSharing planned: No. There is no plan to share data with researchers not involved in this study.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Xue-Jun Kong, MD principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing intranasal oxytocin and oral probiotics in people with Autism Spectrum Disorder, run by Massachusetts General Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Social Responsiveness Scale (SRS) Edition 2 (time frame: change from baseline at 0, 16, and 28 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03337035, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2020.