Transcranial Magnetic Stimulation for Depression in Autism Spectrum Conditions (RESTORE)

Theta Burst Stimulation for Refractory Depression in Autism Spectrum Conditions

In this research study the investigators aim to learn more about the therapeutic effects of a newer form of non-invasive transcranial magnetic stimulation (TMS), called theta burst simulation (TBS), on refractory depression in Autism Spectrum Conditions.

Study Overview

• Status: Completed
• Conditions: Autism Spectrum Disorder; Major Depressive Disorder
• Intervention / Treatment: Procedure: Bilateral TMS; Procedure: Unilateral TMS

Detailed Description

The overarching goal of this study is to examine treatment effects and elucidate the physiological biomarkers of a newer form of non-invasive brain stimulation therapy on refractory depression in a sample of participants with ASC (autism spectrum condition).

Aim 1: To compare the efficacy of 30-sessions of bilateral (BL) versus unilateral (UL) Theta Burst Stimulation to the dorsolateral prefrontal cortex (DLPFC) on depression severity in youth/young adults with ASC and co-occurring refractory major depressive disorder (MDD).

Aim 2: To identify physiological markers of target engagement of successful response to either UL or BL on depression severity in youth with ASC and co-occurring refractory MDD. These physiological markers include high-resolution electroencephalography (EEG) markers, social eye-tracking, and handgrip strength (collected via NIH toolbox's motor toolbox domain).

Aim 3: To identify feasibility of BL and UL in participants with ASC including systematic measures of safety and tolerability. This includes clinical measures such as rate of hospitalization and medication use.

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 26 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Have been diagnosed on the autism spectrum
• Have been diagnosed with depression and have failed one or more evidence-based antidepressant treatments (e.g. a Selective Serotonin Reuptake Inhibitor, talk therapy like Cognitive Behavioral Therapy)
• Do not have an intellectual disability

Exclusion Criteria:

• Substance use disorder
• Presence of metallic foreign bodies or implanted medical devices
• History of epilepsy
• Prior rTMS treatment
• For female subjects of child bearing potential, current pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bilateral; Theta burst stimulation (TBS)	Procedure: Bilateral TMS; Stimulation begins with continuous TBS to the right dorsolateral prefrontal cortex (DLPFC) (120 seconds of uninterrupted bursts; 600 pulses per session) followed by intermittent TBS to the left DLPFC (2 seconds on and 8 seconds off; 600 pulses per session); total duration of 3 min 9 seconds per hemisphere.
Active Comparator: Unilateral; Theta burst stimulation (TBS)	Procedure: Unilateral TMS; Stimulation involves only intermittent TBS to the left DLPFC (2 seconds on and 8 seconds off; 600 pulses per session); total duration of 3 min 9 seconds.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change-from-baseline at 4 weeks in mean Hamilton Depression Rating Scale (HDRS-17) score.	The HDRS-17 is a valid and reliable measure that assesses severity of, and change in, depressive symptoms. HDRS-17 scores range from 0-52, with scores of 0-7 indicating absence or remission of depression, 7-17 indicating mild depression, 18-24 indicating moderate depression, and scores at or over 25 indicating severe depression.	4 weeks post-treatment
Change-from-baseline at 4 weeks in mean and Beck Depression Inventory (BDI-II) scores.	The BDI-II is a valid and reliable measure for assessing the severity of depressive symptoms. BDI-II scores range from 0-63, with scores of 0-10 indicating absence or remission of depression, 11-16 indicating mild mood disturbance, 17-20 indicating borderline clinical depression, 21-30 indicating moderate depression, 31-40 severe depression, and scores over 40 indicating extreme depression.	4 weeks post-treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change-from-baseline at 4 weeks in physiological markers via the use of high-resolution electroencephalography (EEG).	EEG offers a real-time image of cortical excitability and connectivity. We will use power spectral analysis to assess changes in event-related gamma and alpha activity.	4 weeks post-treatment
Change-from-baseline at 4 weeks in handgrip strength or relative handgrip strength.	Handgrip strength is particularly novel and has been shown to be negatively associated with depressive symptoms, making muscle strength a possible clinical marker of poor mental health. The grip strength test from NIH Toolbox's motor domain will be used to collect a digital reading of force in pounds from each participant.	4 weeks post-treatment

Collaborators and Investigators

• Sponsor: Children's Hospital Medical Center, Cincinnati
• Investigators: Principal Investigator: Ernest Pedapati, MD, Children's Hospital Medical Center, Cincinnati

Study record dates

Study Major Dates

• Study Start (Actual): November 24, 2021
• Primary Completion (Actual): February 23, 2023
• Study Completion (Actual): February 23, 2023

Study Registration Dates

• First Submitted: October 28, 2021
• First Submitted That Met QC Criteria: March 4, 2022
• First Posted (Actual): March 9, 2022

Study Record Updates

• Last Update Posted (Actual): February 7, 2024
• Last Update Submitted That Met QC Criteria: February 6, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: depression; autism; MDD; ASD; Transcranial magnetic stimulation; TMS; TBS; theta burst stimulation
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Depression; Depressive Disorder; Autistic Disorder; Autism Spectrum Disorder; Depressive Disorder, Major
• Other Study ID Numbers: 2021-0594

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: all collected IPD
• IPD Sharing Time Frame: upon completion of data collection
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes