TAD: TMS for Adults With Autism and Depression

• Sponsor: Medical University of South Carolina (Other)
• Overall Status: Completed
• CT.gov ID: NCT02939560
• Collaborator: (none)
• Enrollment: 13
• Location: 1
• Arm: 1
• Duration (Months): 24.6
• Patients Per Site Per Month: 0.5

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Autism Spectrum Disorder; Depression; Depressive Disorder; Major Depressive Disorder	Device: NeuroStar® TMS device (Neuronetics, Atlanta, GA)	N/A

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

• Study Type: Interventional
• Actual Enrollment: 13 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Transcranial Magnetic Stimulation for Adults With Autism Spectrum Disorder and Depression
• Study Start Date: Sep 1, 2016
• Actual Primary Completion Date: Jun 1, 2018
• Actual Study Completion Date: Sep 20, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: rTMS Participants will receive rTMS sessions according to the study protocol.	Device: 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).

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

3. 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

4. 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.

5. 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 Outcome Measures

1. Change From Baseline in Functional MRI Scanning During Cognitive Processing Tasks [Baseline, Week 5]

   Functional MRI data during cognitive processing tasks

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts 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

• Exclusion criteria for fMRI scanning:

• 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medical University of South Carolina	Charleston	South Carolina	United States	29425

Sponsors and Collaborators

• Medical University of South Carolina

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 30, 2019

More Information

Additional Information:

• Home page with information about the Primary Investigator

Publications

• Oberman 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. Review.
• 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. Review.

• Responsible Party: Medical University of South Carolina
• ClinicalTrials.gov Identifier: NCT02939560
• Other Study ID Numbers: Pro00056546
• First Posted: Oct 20, 2016
• Last Update Posted: Oct 1, 2019
• Last Verified: Sep 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Medical University of South Carolina: Autism Spectrum Disorder; Autism; Depressive; Depression
• Additional relevant MeSH terms: Disease; Depression; Depressive Disorder; Autistic Disorder; Depressive Disorder, Major; Autism Spectrum Disorder; Child Development Disorders, Pervasive

Study Results

Participant Flow

Arm/Group Title	rTMS
Arm/Group Description	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).
Period Title: Overall Study
STARTED	13
COMPLETED	10
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	rTMS
Arm/Group Description	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).
Overall Participants	13
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	13 100%
>=65 years	0 0%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	25.5
Sex: Female, Male (Count of Participants)
Female	1 7.7%
Male	12 92.3%
Race and Ethnicity Not Collected (Count of Participants)
Region of Enrollment (Count of Participants)
United States	13 100%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Hamilton Depression Rating Scale
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	rTMS
Arm/Group Description	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).
Measure Participants	10
Baseline	21.5 (4.3)
Week 5	10.2 (6.5)

2. Primary Outcome

Title	Change From Baseline in Aberrant Behavior Checklist
Description	Aberrant Behavior Checklist. Minimum 0, maximum 174. Higher scores indicate worse behaviors.
Time Frame	Baseline, Week 5, Week 9, Week 17

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	rTMS
Arm/Group Description	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).
Measure Participants	10
Baseline	53 (28)
Week 5	24 (16)
Week 9	20 (21)
Week 17	30 (28)

3. Primary Outcome

Title	Change From Baseline in Social Responsiveness Scale-2
Description	Social Responsiveness Scale-2. Minimum 0, maximum 195. Higher indicates worse behaviors
Time Frame	Baseline, Week 5, Week 9, Week 17

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	rTMS
Arm/Group Description	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).
Measure Participants	10
Baseline	70.5 (10.6)
Week 5	70.1 (14.3)
Week 9	66.0 (16.6)
Week 17	66.9 (15.0)

4. Primary Outcome

Title	Change From Baseline in Ritvo Autism-Aspergers Diagnostic Scale
Description	Ritvo Autism-Aspergers Diagnostic Scale. Minimum 0, maximum 240. Higher indicates worse symptoms.
Time Frame	Baseline, Week 5, Week 9, Week 17

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	rTMS
Arm/Group Description	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).
Measure Participants	10
Baseline	38 (11)
Week 5	38 (15)
Week 9	39 (14)
Week 17	39 (15)

5. Primary Outcome

Title	Change From Baseline in Repetitive Behavior Scale-Revised
Description	Repetitive Behavior Scale-Revised Global Impression. Minimum 0, maximum 100. Higher indicates worse behaviors
Time Frame	Baseline, Week 5, Week 9, Week 17

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	rTMS
Arm/Group Description	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).
Measure Participants	10
Baseline	59 (26)
Week 5	26 (25)
Week 9	27 (22)
Week 17	30 (18)

6. Secondary Outcome

Title	Change From Baseline in Functional MRI Scanning During Cognitive Processing Tasks
Description	Functional MRI data during cognitive processing tasks
Time Frame	Baseline, Week 5

Outcome Measure Data

Analysis Population Description

Unable to obtain due to lack of available equipment.

Arm/Group Title	rTMS
Arm/Group Description	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).
Measure Participants	0

Adverse Events

Time Frame	Baseline to 17 weeks
Arm/Group Title	rTMS
Arm/Group Description	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).
All Cause Mortality
	rTMS
	Affected / at Risk (%)	# Events
Total	0/13 (0%)
Serious Adverse Events
	rTMS
	Affected / at Risk (%)	# Events
Total	0/13 (0%)
Other (Not Including Serious) Adverse Events
	rTMS
	Affected / at Risk (%)	# Events
Total	1/13 (7.7%)
Nervous system disorders
Seizure	1/13 (7.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.