TMS for Adults With Autism and Depression (TAD)

• ClinicalTrials.gov Identifier: NCT02939560
• Recruitment Status: Completed
• First Posted: October 20, 2016
• Results First Posted: October 1, 2019
• Last Update Posted: October 1, 2019
• Sponsor: Medical University of South Carolina
• Information provided by (Responsible Party): Medical University of South Carolina

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)	Not Applicable

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 (Clinical Trial)
• 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: September 2016
• Actual Primary Completion Date: June 1, 2018
• Actual Study Completion Date: September 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 [ 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.
2. 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.
3. 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
4. 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.
5. 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

Secondary Outcome Measures :

1. Change From Baseline in Functional MRI Scanning During Cognitive Processing Tasks [ Time Frame: Baseline, Week 5 ]
   Functional MRI data during cognitive processing tasks

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

United States, South Carolina

Medical University of South Carolina

Charleston, South Carolina, United States, 29425

Sponsors and Collaborators

Medical University of South Carolina

  Study Documents (Full-Text)

Documents provided by Medical University of South Carolina:

Study Protocol and Statistical Analysis Plan  [PDF] May 30, 2019

More Information

Additional Information:

Home page with information about the Primary Investigator 

Publications of Results:

George 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.

Enticott 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.

Other 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. Review.

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.

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

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: Individual participant data will not be shared.

Keywords provided by Medical University of South Carolina:

Autism Spectrum Disorder; Autism; Depressive; Depression

Additional relevant MeSH terms:

Depression; Depressive Disorder; Autistic Disorder; Depressive Disorder, Major; Autism Spectrum Disorder; Disease; Child Development Disorders, Pervasive; Pathologic Processes; Behavioral Symptoms; Mood Disorders; Mental Disorders; Neurodevelopmental Disorders