TMS and Exposure Therapy

NCT04019054 | Terminated Results DMC FDA Device

• 1 other identifier: 19-000218
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

Spider phobia is an exceedingly common phobia throughout the world. The current standard treatment involves exposure therapy, which consists of a series of brief exposures of an individual to the thing they fear, in this case spiders. This study aims to examine the use of a neuromodulatory technology, transcranial magnetic stimulation (TMS), as a possible treatment option for spider phobia. TMS uses low-intensity electromagnetic energy to stimulate the brain, introducing energy into critical hubs of brain networks to "reset" their function and alleviate symptoms with very few side-effects. This study will consist of four separate visits. After screening subjects for spider phobia, baseline testing of subjective distress measures and physiologic stress data (heart rate variability and sweat response) during a prolonged spider exposure test will be collected. Subjects will then be placed into one of two groups: one receiving exposure therapy and intermittent Theta Burst Stimulation (iTBS) TMS (active study group), and another receiving exposure therapy with iTBS to a circuit not involved in a phobic reaction (control study group). Subjects will undergo their first treatment session during the first visit following the baseline data collection; the second and third treatments will occur the following two days. The fourth visit will occur one week after the third and consist of the same testing as the first visit; the same data will be collected. Changes from pre- to post-treatment in both subjective and physiologic data will be compared between the treatment and sham groups to examine effects of TMS on spider phobia.

Conditions

Arachnophobia; Phobia

Keywords

Transcranial Magnetic Stimulation (TMS); Exposure Therapy; Phobia; Intermittent Theta-Burst Stimulation (iTBS)

Outcome Measures

Primary Outcomes (3)

• Behavioral Approach Test, Change in Steps Completed

  The difference between the number of steps completed during the pre- and post-treatment behavioral approach tests.

  baseline and 1 week after treatment

• Change in Subjective Distress, Klorman Spider Phobia Questionnaire

  Changes in scores on questionnaires regarding distress around spiders (Klorman spider phobia questionnaire). Scored on a scale of 0-31, with higher numbers associated with greater subjective fear of spiders. No subscales reported

  baseline and 1 week

• Change in Subjective Distress, Syzmanski Fear of Spiders Questionnaire

  Changes in scores on questionnaires regarding distress around spiders (Syzmanski Fear of Spiders Questionnaire). 18 items each scored on a scale of 1-7 (total score ranging 18-126), with higher numbers associated with greater subjective fear of spiders. No subscales reported

  baseline and 1 week

Secondary Outcomes (4)

• Behavioral Approach Test, Change in Skin Conductance

  baseline and 1 week after treatment

• Change in Subjective Anticipatory Distress, Behavioral Approach Test

  baseline and 1 week, difference reported

• Average Treatment Intensity Tolerated

  Average tolerated intensity during TMS treatment sessions (days 1, 2, and 3 of treatment)

• Change in Subjective Maximum Distress, Behavioral Approach Test

  baseline and 1 week, change in scores from pre to post reported

Other Outcomes (2)

• Pain Score

  Days 1, 2, and 3 (after each TMS treatment)

• Group Assignment Conjecture

  Immediately following repeat behavioral approach testing (i.e. the very last activity of the final/4th/followup visit).

Study Arms (2)

Active iTBS, Ventromedial Prefrontal Cortex (vmPFC)

EXPERIMENTAL

Stimulation intensity of 100% of the individual resting motor threshold in bursts of three pulses at a frequency of 50 Hz every 200 ms on top of a 5Hz carrier wave. Pulse delivery is over 2 s and repeated every 10 s, 20 times in succession, for a total of 600 pulses delivered in 3.33 minutes. Delivered over vmPFC, as determined by position Fpz of the international 10-20 EEG electrode system.

Device: Intermittent Theta Burst Stimulation (iTBS), Ventromedial Prefrontal Cortex (vmPFC)

Control iTBS, vertex

PLACEBO COMPARATOR

Stimulation intensity of 100% of the individual resting motor threshold in bursts of three pulses at a frequency of 50 Hz every 200 ms on top of a 5Hz carrier wave. Pulse delivery is over 2 s and repeated every 10 s, 20 times in succession, for a total of 600 pulses delivered in 3.33 minutes. Delivered over vertex, as determined by position Cz of the international 10-20 EEG electrode system.

Device: Intermittent Theta Burst Stimulation (iTBS), vertex

Interventions

Intermittent Theta Burst Stimulation (iTBS), Ventromedial Prefrontal Cortex (vmPFC) DEVICE

iTBS delivered to vmPFC for active treatment of spider phobia.

Active iTBS, Ventromedial Prefrontal Cortex (vmPFC)

Intermittent Theta Burst Stimulation (iTBS), vertex DEVICE

iTBS delivered to vertex for placebo treatment of spider phobia.

Control iTBS, vertex

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• At least 18 years of age
• English-speaking
• Spider phobia as determined by a Spider Phobia Questionnaire (SPQ; Klorman et al 1974) score of at least 17/30

You may not qualify if:

• Subject is mentally or legally incapacitated, unable to give informed consent.
• Subjects with psychosis (psychotic depression, schizophrenia, or schizoaffective diagnoses (lifetime)); bipolar disorder (lifetime); dementia (lifetime); delirium within the past 6 months; eating disorder within the past year; obsessive-compulsive disorder (lifetime); post-traumatic stress disorder within the past year; acute risk for suicide or self-injurious behavior. Patients with diagnostic uncertainty or ambiguity (e.g. rule-out pseudodementia of depression) will be excluded.
• Subjects with a HamD suicidality item score of '3' or '4,' corresponding to "suicidal ideas or gestures" or "attempts at suicide," will be excluded.
• Subjects with exposure to ECT within the past 6 months, previous TMS treatment for any condition, or VNS treatment (lifetime).
• Past history of skull fracture; cranial surgery entering the calvarium; space occupying intracranial lesion; stroke, CVA, or TIAs; cerebral aneurysm; Parkinson's or Huntington's disease; or Multiple Sclerosis.
• Any history of intracranial implant including cochlear implant, implanted electrodes/stimulators, aneursym clips or coils, stents, bullet fragments; implanted cardiac pacemaker, defibrillator, vagus nerve stimulator, deep brain stimulator; or other implanted devices or objects contraindicated by product labeling.
• Neurological conditions including epilepsy, cerebrovascular disease, dementia, increased intracranial pressure, history of repetitive or severe head trauma, or with primary or secondary tumors in the CNS.
• current pregnancy or breast feeding. The effects of TMS on pregnant and breastfeeding patients has not been systematically studied.
• Infection or loss of integrity of skin over the forehead, where the device will be positioned.
• Increased risk of seizure as indicated by: a) history (or family history) of seizure or epilepsy; b) history of stroke, head injury, or unexplained seizures; c) concurrent medication use such as tricyclic antidepressants, neuroleptic medications, or other drugs that are known to lower the seizure threshold; d) secondary conditions that may significantly alter electrolyte balance or lower seizure threshold; e) no quantifiable motor threshold such that TMS dosage cannot be accurately determined.
• Known bee, insect, or arachnid allergy
• Other medical contraindications to any of the study procedures.

Sponsors & Collaborators

• University of California, Los Angeles: lead

Study Sites (1)

University of California, Los Angeles

Los Angeles, California, 90095, United States

Location

Related Publications (25)

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MeSH Terms

Conditions

Arachnophobia; Phobic Disorders

Condition Hierarchy (Ancestors)

Anxiety Disorders; Mental Disorders

Limitations and Caveats

1. Early termination leading to small numbers of subjects analyzed and limited statistical analysis (in part due to COVID) 2. Equipment limitations and technical problems with physiologic data measurement leading to intermittent unreliable/uninterpretable data 3. Brief duration of treatment contributing to lack of differentiation between experimental groups

Results Point of Contact

• Title: Dr. Michael K. Leuchter
• Organization: UCLA Psychiatry

mkleuchter@mednet.ucla.edu

3108906943

Study Officials

• Michael K Leuchter, B.S.

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

• Marco Iacoboni, M.D., Ph.D.

  Professor, UCLA Psychiatry and Biobehavioral Science

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Assignment will be performed randomly and tracked by clinical staff involved with the TMS treatment itself, and research staff assessing outcomes and analyzing data will be blinded to groups until after analysis is complete.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Student, David Geffen School of Medicine

Model Details: Participants will be randomly assigned to either the study treatment (iTBS stimulation to the ventromedial prefrontal cortex) or control treatment (iTBS stimulation to the vertex). Treatments will occur immediately following exposure therapy (both groups will undergo identical exposure therapy), and groups will receive iTBS to the same site for all three treatments

Study Record Dates

• First Submitted: July 7, 2019
• First Posted: July 15, 2019
• Study Start: August 19, 2019
• Primary Completion: March 15, 2020
• Study Completion: March 18, 2020
• Last Updated: April 1, 2021
• Results First Posted: April 1, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)