Autism Spectrum Disorder, Depression, Depressive Disorder, Major Depressive Disorder
Conditions
Keywords
Autism Spectrum Disorder, Autism, Depressive, Depression
Brief 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). 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.
Interventions
DEVICENeuroStar® 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).
Sponsors
Medical University of South Carolina
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Diagnosis of Autism Spectrum Disorder and active depressive symptoms.
Exclusion criteria
* 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 *
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hamilton Depression Rating Scale | 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 | 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 | 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 | 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 | Baseline, Week 5, Week 9, Week 17 | Repetitive Behavior Scale-Revised Global Impression. Minimum 0, maximum 100. Higher indicates worse behaviors |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Functional MRI Scanning During Cognitive Processing Tasks | Baseline, Week 5 | Functional MRI data during cognitive processing tasks |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| rTMS Participants will receive rTMS sessions according to the study protocol.
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). | 13 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Protocol Violation | 1 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | rTMS | — |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | — |
| Age, Categorical >=65 years | 0 Participants | — |
| Age, Categorical Between 18 and 65 years | 13 Participants | — |
| Age, Continuous | 25.5 years | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment United States | 13 Participants | — |
| Sex: Female, Male Female | 1 Participants | — |
| Sex: Female, Male Male | 12 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 13 |
| other Total, other adverse events | 1 / 13 |
| serious Total, serious adverse events | 0 / 13 |
Outcome results
Primary
Change From Baseline in Aberrant Behavior Checklist
Aberrant Behavior Checklist. Minimum 0, maximum 174. Higher scores indicate worse behaviors.
Time frame: Baseline, Week 5, Week 9, Week 17
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| rTMS | Change From Baseline in Aberrant Behavior Checklist | Baseline | 53 score on a scale | Standard Deviation 28 |
| rTMS | Change From Baseline in Aberrant Behavior Checklist | Week 5 | 24 score on a scale | Standard Deviation 16 |
| rTMS | Change From Baseline in Aberrant Behavior Checklist | Week 9 | 20 score on a scale | Standard Deviation 21 |
| rTMS | Change From Baseline in Aberrant Behavior Checklist | Week 17 | 30 score on a scale | Standard Deviation 28 |
Primary
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.
Time frame: Baseline through Week 5
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| rTMS | Change From Baseline in Hamilton Depression Rating Scale | Baseline | 21.5 score on a scale | Standard Deviation 4.3 |
| rTMS | Change From Baseline in Hamilton Depression Rating Scale | Week 5 | 10.2 score on a scale | Standard Deviation 6.5 |
Primary
Change From Baseline in Repetitive Behavior Scale-Revised
Repetitive Behavior Scale-Revised Global Impression. Minimum 0, maximum 100. Higher indicates worse behaviors
Time frame: Baseline, Week 5, Week 9, Week 17
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| rTMS | Change From Baseline in Repetitive Behavior Scale-Revised | Baseline | 59 units on a scale | Standard Deviation 26 |
| rTMS | Change From Baseline in Repetitive Behavior Scale-Revised | Week 5 | 26 units on a scale | Standard Deviation 25 |
| rTMS | Change From Baseline in Repetitive Behavior Scale-Revised | Week 9 | 27 units on a scale | Standard Deviation 22 |
| rTMS | Change From Baseline in Repetitive Behavior Scale-Revised | Week 17 | 30 units on a scale | Standard Deviation 18 |
Primary
Change From Baseline in Ritvo Autism-Aspergers Diagnostic Scale
Ritvo Autism-Aspergers Diagnostic Scale. Minimum 0, maximum 240. Higher indicates worse symptoms.
Time frame: Baseline, Week 5, Week 9, Week 17
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| rTMS | Change From Baseline in Ritvo Autism-Aspergers Diagnostic Scale | Baseline | 38 score on a scale | Standard Deviation 11 |
| rTMS | Change From Baseline in Ritvo Autism-Aspergers Diagnostic Scale | Week 5 | 38 score on a scale | Standard Deviation 15 |
| rTMS | Change From Baseline in Ritvo Autism-Aspergers Diagnostic Scale | Week 9 | 39 score on a scale | Standard Deviation 14 |
| rTMS | Change From Baseline in Ritvo Autism-Aspergers Diagnostic Scale | Week 17 | 39 score on a scale | Standard Deviation 15 |
Primary
Change From Baseline in Social Responsiveness Scale-2
Social Responsiveness Scale-2. Minimum 0, maximum 195. Higher indicates worse behaviors
Time frame: Baseline, Week 5, Week 9, Week 17
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| rTMS | Change From Baseline in Social Responsiveness Scale-2 | Baseline | 70.5 score on a scale | Standard Deviation 10.6 |
| rTMS | Change From Baseline in Social Responsiveness Scale-2 | Week 5 | 70.1 score on a scale | Standard Deviation 14.3 |
| rTMS | Change From Baseline in Social Responsiveness Scale-2 | Week 9 | 66.0 score on a scale | Standard Deviation 16.6 |
| rTMS | Change From Baseline in Social Responsiveness Scale-2 | Week 17 | 66.9 score on a scale | Standard Deviation 15 |
Secondary
Change From Baseline in Functional MRI Scanning During Cognitive Processing Tasks
Functional MRI data during cognitive processing tasks
Time frame: Baseline, Week 5
Population: Unable to obtain due to lack of available equipment.