Autism Spectrum DisorderTADNCT02939560
TMS for Adults With Autism and Depression
A study testing NeuroStar® TMS device (Neuronetics, Atlanta, GA) in people with Autism Spectrum Disorder and Depression, run by Medical University of South Carolina at 1 site in United States.
Trial summary
The goal of this proposal is to investigate whether a standard rTMS protocol for depression, including multiple sessions applied to left dorsolateral prefrontal cortex (DLPFC) results in reduction of depressive symptoms for adult patients with ASD and MDD (Aim 1). Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Autism Spectrum Disorder, Depression, Depressive Disorder
- What is being tested?
- NeuroStar® TMS device (Neuronetics, Atlanta, GA)
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2016to 20 Sep 2018
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Diagnosis of Autism Spectrum Disorder and active depressive symptoms.
Who cannot join
- List specific contraindicationsUncontrolled and/or untreated seizure disorder as defined by any incidence of seizure within the past 6 months. Patients with diagnosed epilepsy, or prior seizures, will be allowed in the study if they are taking an anticonvulsant medication, or have not had a seizure in the past year off medications.
- Moderate to severe intellectual disability (ID) as defined by IQ < 60, determined by prior IQ testing or Wechsler Abbreviated Scale of Intelligence (WASC-II) if no prior test results available
- Other psychiatric or neurodevelopmental illness that is the primary area of clinical focus (including but not limited to primary psychotic disorder, substance abuse disorder, and ASD or ID which are secondary to genetic syndromes)
- Active suicidal ideation or suicide attempt in the 90 days prior to initial assessment
- Presence of any metal implants or devices in the head or neck (e.g. metal plates or screws)
- No participants who are pregnant or who are planning to become pregnant
Show all 21Show fewer
- have metal pins, plates or clips in the body or have orthodontics
- have surgical implants such as pacemakers or cochlear implants
- have permanent makeup or tattoos near the face or head
- have metal fragments in the body (from welding, shrapnel, BB guns) or suspect that they have fragments
- are claustrophobic
- are pregnant
- have ever suffered a closed head injury or concussion
- are currently under the influence of alcohol or other recreational drugs
- are a smoker
- are currently enrolled in a course in which the PI or co-I's are instructors
- cannot understand the task instructions
- cannot lay still in the mock scanner for a period of 6 minutes
- Inability or unwillingness of participant or legal guardian/representative to give informed consent
- There will be no discrimination or exclusions based on race, gender, sexual orientation, or other socioeconomic factors. Of note, while both male and female participants will be actively and equally recruited using the same methods. The natural distribution of autism in the population skews towards significant towards male gender, with male prevalence being 4-5 times that of female prevalence. Our study will therefore likely have more male participants than female due to this trend in prevalence.
- Children (age <18) are being excluded from this study for several reasons. While autism is a pediatric neurodevelopmental disorder with symptom onset as young as one year of age, it is also one that is chronic throughout adulthood. Both children with autism and neurotypical children undergo periods of rapid change in brain size, structure, and organization as they age, and the interaction between a full rTMS series and brains that are still involved in periods of very active development and whom may also be at different points along their own developmental timelines may skew or alter the data that is collected. Additionally, due to both brain growth and increases in skull thickness, children of different ages may have significantly different "scalp to cortex" distances, which can result in very different patterns of cortical stimulation despite uniform coil positioning. This will be an added, unnecessary variable which would compromise the attempt at performing a standardized protocol. Finally, while high frequency rTMS is an FDA approved treatment for depression in adults, it has not yet been FDA approved in children and adolescents.
Trial locations and contacts
1 site in 1 country.
United States1 site
Medical University of South Carolina
Charleston, South Carolina, 29425
About this study
Official title: Transcranial Magnetic Stimulation for Adults With Autism Spectrum Disorder and Depression
The goal of this proposal is to investigate whether a standard rTMS protocol for depression, including multiple sessions applied to left dorsolateral prefrontal cortex (DLPFC) results in reduction of depressive symptoms for adult patients with ASD and MDD (Aim 1). The secondary goal is to investigate and whether there is any beneficial reduction in the core symptoms of autism (Aim 2).
Read the detailed description
Aim 1. Determine the safety and therapeutic efficacy of left-sided DLPFC high frequency rTMS on MDD symptoms in patients with ASD: The investigators hypothesize that patients receiving the rTMS will tolerate the treatment course without difficulty and have clinically significant reduction of depressive symptoms after receiving all 25 sessions, as compared with their symptom burden prior to initiating TMS. Depression symptom data will be collected as pre- and post-TMS scores on Hamilton Depression Rating Scale (HAM-D). Depression scores will also be monitored periodically during course of TMS with Patient Health Questionnaires (PHQ-9).
Exploratory sub-aim - Monitoring for durability of response: The investigators hypothesize that subjects receiving rTMS will demonstrate durability of response in their depression symptom reduction, as measured by HAM-D scores at 1 month and 3 months post-TMS.
Aim 2. Determine the effect of left DLPFC rTMS on core symptoms of ASD: The investigators hypothesize that subjects will experience reduction in core symptoms of ASD after completing all 25 sessions, as compared with their symptom burden prior to initiating treatment. For social and communication deficits, informant and/or self-report evaluations will be made pre- and post-TMS with the Social Responsiveness Scale (SRS), the Ritvo Autism Aspergers Diagnostic Scale-Revised (RAADS-R) and the Aberrant Behavior Checklist (ABC). Repetitive and restricted behavior will be evaluated using the Repetitive Behavior Scale-Revised (RBS-R), the ABC, and RAADS.
Exploratory sub-aim: Determine if there are changes to functional brain connectivity during face and object processing tasks via functional MRI imaging in patients with Autism who receive rTMS: The study investigators hypothesize that there will be altered brain connectivity evident in patients' baseline fMRI during cognitive processing tasks prior to TMS reflected as both hyper- and hypo-connectivity, and that there will be some level of normalization of these patterns in fMRI after completion of TMS series, particularly in the prefrontal cortex.
Exploratory sub-aim - Monitoring for durability of response: The study investigators hypothesize that subjects receiving rTMS will exhibit durability of response in their ASD symptom reduction, as measured by ABC, SRS, RAADS, AND RBR scores at 1 month and 3 months post-TMS.
- Being tested
- NeuroStar® TMS device (Neuronetics, Atlanta, GA)
- Keywords
- Autism Spectrum Disorder, Autism, Depressive, Depression
- Medical subject headings
- Autism Spectrum Disorder, Depression, Depressive Disorder, Depressive Disorder, Major, Autistic Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NeuroStar® TMS device (Neuronetics, Atlanta, GA)Device
Participants in this study arm will be evaluated before and after receiving rTMS. Outcome measures will include social skills rating scales, depression rating scales and cognitive tasks while undergoing functional magnetic resonance imaging (fMRI).
| Study group | Role | What they receive |
|---|---|---|
| rTMS | Experimental | Participants will receive rTMS sessions according to the study protocol. Receives: Device: NeuroStar® TMS device (Neuronetics, Atlanta, GA) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Hamilton Depression Rating Scale
Hamilton Depression Rating Scale (HAM-D) with 17 questions. Minimum score = 0, maximum 53. Higher scores mean more severe depression.
Measured: Baseline through Week 5
Change From Baseline in Aberrant Behavior Checklist
Aberrant Behavior Checklist. Minimum 0, maximum 174. Higher scores indicate worse behaviors.
Measured: Baseline, Week 5, Week 9, Week 17
Change From Baseline in Social Responsiveness Scale-2
Social Responsiveness Scale-2. Minimum 0, maximum 195. Higher indicates worse behaviors
Measured: Baseline, Week 5, Week 9, Week 17
Change From Baseline in Ritvo Autism-Aspergers Diagnostic Scale
Ritvo Autism-Aspergers Diagnostic Scale. Minimum 0, maximum 240. Higher indicates worse symptoms.
Measured: Baseline, Week 5, Week 9, Week 17
Change From Baseline in Repetitive Behavior Scale-Revised
Repetitive Behavior Scale-Revised Global Impression. Minimum 0, maximum 100. Higher indicates worse behaviors
Measured: Baseline, Week 5, Week 9, Week 17
Secondary outcomes (1)
Change From Baseline in Functional MRI Scanning During Cognitive Processing Tasks
Functional MRI data during cognitive processing tasks
Measured: Baseline, Week 5
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2016 (estimated)
- Study startSep 2016
- Primary completion1 Jun 2018
- Study completion20 Sep 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)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 Medical University of South CarolinaThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical University of South Carolina
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02939560
- Sponsor's protocol ID
- Pro00056546
- Acronym
- TAD
- Status last verified
- Sep 2019
- First submitted
- 29 Sep 2016
- Last updated
- 1 Oct 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No: Individual participant data will not be shared.
Publications
Perera T, George MS, Grammer G, Janicak PG, Pascual-Leone A, Wirecki TS. The Clinical TMS Society Consensus Review and Treatment Recommendations for TMS Therapy for Major Depressive Disorder. Brain Stimul. 2016 May-Jun;9(3):336-346. doi: 10.1016/j.brs.2016.03.010. Epub 2016 Mar 16.
PubMed 27090022Oberman LM, Enticott PG, Casanova MF, Rotenberg A, Pascual-Leone A, McCracken JT; TMS in ASD Consensus Group. Transcranial magnetic stimulation in autism spectrum disorder: Challenges, promise, and roadmap for future research. Autism Res. 2016 Feb;9(2):184-203. doi: 10.1002/aur.1567. Epub 2015 Nov 4.
PubMed 26536383George MS, Raman R, Benedek DM, Pelic CG, Grammer GG, Stokes KT, Schmidt M, Spiegel C, Dealmeida N, Beaver KL, Borckardt JJ, Sun X, Jain S, Stein MB. A two-site pilot randomized 3 day trial of high dose left prefrontal repetitive transcranial magnetic stimulation (rTMS) for suicidal inpatients. Brain Stimul. 2014 May-Jun;7(3):421-31. doi: 10.1016/j.brs.2014.03.006. Epub 2014 Mar 19.
PubMed 24731434Enticott PG, Fitzgibbon BM, Kennedy HA, Arnold SL, Elliot D, Peachey A, Zangen A, Fitzgerald PB. A double-blind, randomized trial of deep repetitive transcranial magnetic stimulation (rTMS) for autism spectrum disorder. Brain Stimul. 2014 Mar-Apr;7(2):206-11. doi: 10.1016/j.brs.2013.10.004. Epub 2013 Oct 27.
PubMed 24280031
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Transcranial Magnetic Stimulation for Adults With Autism Spectrum Disorder and Depression
- ClinicalTrials.gov ID
- NCT02939560
- Acronym / sponsor ID
- TAD / Pro00056546
- Keywords
- Autism Spectrum Disorder, Autism, Depressive, Depression
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Medical University of South CarolinaUniversity, hospital or other
- Study start
- Sep 2016
- Primary completion
- 1 Jun 2018 (actual)
- Study completion
- 20 Sep 2018 (actual)
- First posted
- 20 Oct 2016 (estimated)
- Results
- Posted 1 Oct 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this proposal is to investigate whether a standard rTMS protocol for depression, including multiple sessions applied to left dorsolateral prefrontal cortex (DLPFC) results in reduction of depressive symptoms for adult patients with ASD and MDD (Aim 1). The secondary goal is to investigate and whether there is any beneficial reduction in the core symptoms of autism (Aim 2).
Detailed description
Aim 1. Determine the safety and therapeutic efficacy of left-sided DLPFC high frequency rTMS on MDD symptoms in patients with ASD: The investigators hypothesize that patients receiving the rTMS will tolerate the treatment course without difficulty and have clinically significant reduction of depressive symptoms after receiving all 25 sessions, as compared with their symptom burden prior to initiating TMS. Depression symptom data will be collected as pre- and post-TMS scores on Hamilton Depression Rating Scale (HAM-D). Depression scores will also be monitored periodically during course of TMS with Patient Health Questionnaires (PHQ-9).
Exploratory sub-aim - Monitoring for durability of response: The investigators hypothesize that subjects receiving rTMS will demonstrate durability of response in their depression symptom reduction, as measured by HAM-D scores at 1 month and 3 months post-TMS.
Aim 2. Determine the effect of left DLPFC rTMS on core symptoms of ASD: The investigators hypothesize that subjects will experience reduction in core symptoms of ASD after completing all 25 sessions, as compared with their symptom burden prior to initiating treatment. For social and communication deficits, informant and/or self-report evaluations will be made pre- and post-TMS with the Social Responsiveness Scale (SRS), the Ritvo Autism Aspergers Diagnostic Scale-Revised (RAADS-R) and the Aberrant Behavior Checklist (ABC). Repetitive and restricted behavior will be evaluated using the Repetitive Behavior Scale-Revised (RBS-R), the ABC, and RAADS.
Exploratory sub-aim: Determine if there are changes to functional brain connectivity during face and object processing tasks via functional MRI imaging in patients with Autism who receive rTMS: The study investigators hypothesize that there will be altered brain connectivity evident in patients' baseline fMRI during cognitive processing tasks prior to TMS reflected as both hyper- and hypo-connectivity, and that there will be some level of normalization of these patterns in fMRI after completion of TMS series, particularly in the prefrontal cortex.
Exploratory sub-aim - Monitoring for durability of response: The study investigators hypothesize that subjects receiving rTMS will exhibit durability of response in their ASD symptom reduction, as measured by ABC, SRS, RAADS, AND RBR scores at 1 month and 3 months post-TMS.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| rTMS | Experimental | Device: NeuroStar® TMS device (Neuronetics, Atlanta, GA)Participants will receive rTMS sessions according to the study protocol. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Diagnosis of Autism Spectrum Disorder and active depressive symptoms.
Key exclusion criteria (21 listed)
- List specific contraindicationsUncontrolled and/or untreated seizure disorder as defined by any incidence of seizure within the past 6 months. Patients with diagnosed epilepsy, or prior seizures, will be allowed in the study if they are taking an anticonvulsant medication, or have not had a seizure in the past year off medications.
- Moderate to severe intellectual disability (ID) as defined by IQ < 60, determined by prior IQ testing or Wechsler Abbreviated Scale of Intelligence (WASC-II) if no prior test results available
- Other psychiatric or neurodevelopmental illness that is the primary area of clinical focus (including but not limited to primary psychotic disorder, substance abuse disorder, and ASD or ID which are secondary to genetic syndromes)
- Active suicidal ideation or suicide attempt in the 90 days prior to initial assessment
- Presence of any metal implants or devices in the head or neck (e.g. metal plates or screws)
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 |
|---|---|---|
| NeuroStar® TMS device (Neuronetics, Atlanta, GA)Participants in this study arm will be evaluated before and after receiving rTMS. Outcome measures will include social skills rating scales, depression rating scales and cognitive tasks while undergoing functional magnetic resonance imaging (fMRI). | Device | rTMS |
Primary outcome
Change From Baseline in Hamilton Depression Rating Scale
Time frame: Baseline through Week 5
Hamilton Depression Rating Scale (HAM-D) with 17 questions. Minimum score = 0, maximum 53. Higher scores mean more severe depression.
Change From Baseline in Aberrant Behavior Checklist
Time frame: Baseline, Week 5, Week 9, Week 17
Aberrant Behavior Checklist. Minimum 0, maximum 174. Higher scores indicate worse behaviors.
Change From Baseline in Social Responsiveness Scale-2
Time frame: Baseline, Week 5, Week 9, Week 17
Social Responsiveness Scale-2. Minimum 0, maximum 195. Higher indicates worse behaviors
Change From Baseline in Ritvo Autism-Aspergers Diagnostic Scale
Time frame: Baseline, Week 5, Week 9, Week 17
Ritvo Autism-Aspergers Diagnostic Scale. Minimum 0, maximum 240. Higher indicates worse symptoms.
Change From Baseline in Repetitive Behavior Scale-Revised
Time frame: Baseline, Week 5, Week 9, Week 17
Repetitive Behavior Scale-Revised Global Impression. Minimum 0, maximum 100. Higher indicates worse behaviors
1 secondary outcome
Change From Baseline in Functional MRI Scanning During Cognitive Processing Tasks
Time frame: Baseline, Week 5
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Oct 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 27090022Perera T, George MS, Grammer G, Janicak PG, Pascual-Leone A, Wirecki TS. The Clinical TMS Society Consensus Review and Treatment Recommendations for TMS Therapy for Major Depressive Disorder. Brain Stimul. 2016 May-Jun;9(3):336-346. doi: 10.1016/j.brs.2016.03.010. Epub 2016 Mar 16.
- Background: PubMed 26536383Oberman LM, Enticott PG, Casanova MF, Rotenberg A, Pascual-Leone A, McCracken JT; TMS in ASD Consensus Group. Transcranial magnetic stimulation in autism spectrum disorder: Challenges, promise, and roadmap for future research. Autism Res. 2016 Feb;9(2):184-203. doi: 10.1002/aur.1567. Epub 2015 Nov 4.
- Results publication: PubMed 24731434George MS, Raman R, Benedek DM, Pelic CG, Grammer GG, Stokes KT, Schmidt M, Spiegel C, Dealmeida N, Beaver KL, Borckardt JJ, Sun X, Jain S, Stein MB. A two-site pilot randomized 3 day trial of high dose left prefrontal repetitive transcranial magnetic stimulation (rTMS) for suicidal inpatients. Brain Stimul. 2014 May-Jun;7(3):421-31. doi: 10.1016/j.brs.2014.03.006. Epub 2014 Mar 19.
- Results publication: PubMed 24280031Enticott PG, Fitzgibbon BM, Kennedy HA, Arnold SL, Elliot D, Peachey A, Zangen A, Fitzgerald PB. A double-blind, randomized trial of deep repetitive transcranial magnetic stimulation (rTMS) for autism spectrum disorder. Brain Stimul. 2014 Mar-Apr;7(2):206-11. doi: 10.1016/j.brs.2013.10.004. Epub 2013 Oct 27.
- Home page with information about the Primary InvestigatorLink provided by the sponsor.
- Individual participant dataSharing planned: No. Individual participant data will not be shared.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing NeuroStar® TMS device (Neuronetics, Atlanta, GA) in people with Autism Spectrum Disorder and Depression, run by Medical University of South Carolina 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 1 inclusion and 21 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 1 Oct 2019. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Oct 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change From Baseline in Hamilton Depression Rating Scale (time frame: Baseline through Week 5). The study lists 5 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 NCT02939560, which also lists 4 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 1 Oct 2019.