Phobia Clinical Trial
Official title:
Transcranial Magnetic Stimulation (TMS) in Conjunction With Exposure Therapy for the Treatment of Spider Phobia
Verified date | March 2021 |
Source | University of California, Los Angeles |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Terminated |
Enrollment | 22 |
Est. completion date | March 18, 2020 |
Est. primary completion date | March 15, 2020 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: 1. At least 18 years of age 2. English-speaking 3. Spider phobia as determined by a Spider Phobia Questionnaire (SPQ; Klorman et al 1974) score of at least 17/30 Exclusion Criteria: 1. Subject is mentally or legally incapacitated, unable to give informed consent. 2. 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. 3. Subjects with a HamD suicidality item score of '3' or '4,' corresponding to "suicidal ideas or gestures" or "attempts at suicide," will be excluded. 4. Subjects with exposure to ECT within the past 6 months, previous TMS treatment for any condition, or VNS treatment (lifetime). 5. 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. 6. 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. 7. 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. 8. current pregnancy or breast feeding. The effects of TMS on pregnant and breastfeeding patients has not been systematically studied. 9. Infection or loss of integrity of skin over the forehead, where the device will be positioned. 10. 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. 11. Known bee, insect, or arachnid allergy 12. Other medical contraindications to any of the study procedures. |
Country | Name | City | State |
---|---|---|---|
United States | University of California, Los Angeles | Los Angeles | California |
Lead Sponsor | Collaborator |
---|---|
University of California, Los Angeles |
United States,
Appelhans, B. M., & Luecken, L. J. (2006). Heart rate variability as an index of regulated emotional responding. Review of General Psychology, 10(3), 229-240. http://doi.org/10.1037/1089-2680.10.3.229
Baeken C, De Raedt R, Van Schuerbeek P, Vanderhasselt MA, De Mey J, Bossuyt A, Luypaert R. Right prefrontal HF-rTMS attenuates right amygdala processing of negatively valenced emotional stimuli in healthy females. Behav Brain Res. 2010 Dec 25;214(2):450-5. doi: 10.1016/j.bbr.2010.06.029. Epub 2010 Jul 1. — View Citation
Bulteau S, Sébille V, Fayet G, Thomas-Ollivier V, Deschamps T, Bonnin-Rivalland A, Laforgue E, Pichot A, Valrivière P, Auffray-Calvier E, Fortin J, Péréon Y, Vanelle JM, Sauvaget A. Efficacy of intermittent Theta Burst Stimulation (iTBS) and 10-Hz high-frequency repetitive transcranial magnetic stimulation (rTMS) in treatment-resistant unipolar depression: study protocol for a randomised controlled trial. Trials. 2017 Jan 13;18(1):17. doi: 10.1186/s13063-016-1764-8. — View Citation
Choi KH, Kim J, Kwon OS, Kim MJ, Ryu YH, Park JE. Is heart rate variability (HRV) an adequate tool for evaluating human emotions? - A focus on the use of the International Affective Picture System (IAPS). Psychiatry Res. 2017 May;251:192-196. doi: 10.1016/j.psychres.2017.02.025. Epub 2017 Feb 11. — View Citation
Christopoulos, G. I., Uy, M. A., & Yap, W. J. (2016). The Body and the Brain: Measuring Skin Conductance Responses to Understand the Emotional Experience. Organizational Research Methods, 1-27. http://doi.org/10.1177/1094428116681073
Chung SW, Hoy KE, Fitzgerald PB. Theta-burst stimulation: a new form of TMS treatment for depression? Depress Anxiety. 2015 Mar;32(3):182-92. doi: 10.1002/da.22335. Epub 2014 Nov 28. Review. — View Citation
Demitrack MA, Thase ME. Clinical significance of transcranial magnetic stimulation (TMS) in the treatment of pharmacoresistant depression: synthesis of recent data. Psychopharmacol Bull. 2009;42(2):5-38. Review. — View Citation
Deppermann S, Notzon S, Kroczek A, Rosenbaum D, Haeussinger FB, Diemer J, Domschke K, Fallgatter AJ, Ehlis AC, Zwanzger P. Functional co-activation within the prefrontal cortex supports the maintenance of behavioural performance in fear-relevant situations before an iTBS modulated virtual reality challenge in participants with spider phobia. Behav Brain Res. 2016 Jul 1;307:208-17. doi: 10.1016/j.bbr.2016.03.028. Epub 2016 Mar 17. — View Citation
Duecker F, Sack AT. Rethinking the role of sham TMS. Front Psychol. 2015 Feb 26;6:210. doi: 10.3389/fpsyg.2015.00210. eCollection 2015. — View Citation
Foltys H, Sparing R, Boroojerdi B, Krings T, Meister IG, Mottaghy FM, Töpper R. Motor control in simple bimanual movements: a transcranial magnetic stimulation and reaction time study. Clin Neurophysiol. 2001 Feb;112(2):265-74. — View Citation
Guhn A, Dresler T, Andreatta M, Müller LD, Hahn T, Tupak SV, Polak T, Deckert J, Herrmann MJ. Medial prefrontal cortex stimulation modulates the processing of conditioned fear. Front Behav Neurosci. 2014 Feb 18;8:44. doi: 10.3389/fnbeh.2014.00044. eCollection 2014. — View Citation
Guhn A, Dresler T, Hahn T, Mühlberger A, Ströhle A, Deckert J, Herrmann MJ. Medial prefrontal cortex activity during the extinction of conditioned fear: an investigation using functional near-infrared spectroscopy. Neuropsychobiology. 2012 Jun;65(4):173-82. doi: 10.1159/000337002. Epub 2012 Apr 26. — View Citation
Jung J, Bungert A, Bowtell R, Jackson SR. Vertex Stimulation as a Control Site for Transcranial Magnetic Stimulation: A Concurrent TMS/fMRI Study. Brain Stimul. 2016 Jan-Feb;9(1):58-64. doi: 10.1016/j.brs.2015.09.008. Epub 2015 Sep 25. — View Citation
Klorman, R., Weerts, T. C., Hastings, J. E., Melamed, B. G., & Lang, P. J. (1974). Psychometric description of some specific-fear questionnaires. Behavior Therapy, 5(3), 401-409. http://doi.org/10.1016/S0005-7894(74)80008-0
Laine CM, Spitler KM, Mosher CP, Gothard KM. Behavioral triggers of skin conductance responses and their neural correlates in the primate amygdala. J Neurophysiol. 2009 Apr;101(4):1749-54. doi: 10.1152/jn.91110.2008. Epub 2009 Jan 14. — View Citation
Leuchter AF, Hunter AM, Krantz DE, Cook IA. Rhythms and blues: modulation of oscillatory synchrony and the mechanism of action of antidepressant treatments. Ann N Y Acad Sci. 2015 May;1344:78-91. doi: 10.1111/nyas.12742. Epub 2015 Mar 23. Review. — View Citation
Mutz J, Edgcumbe DR, Brunoni AR, Fu CHY. Efficacy and acceptability of non-invasive brain stimulation for the treatment of adult unipolar and bipolar depression: A systematic review and meta-analysis of randomised sham-controlled trials. Neurosci Biobehav Rev. 2018 Sep;92:291-303. doi: 10.1016/j.neubiorev.2018.05.015. Epub 2018 May 12. — View Citation
Notzon S, Deppermann S, Fallgatter A, Diemer J, Kroczek A, Domschke K, Zwanzger P, Ehlis AC. Psychophysiological effects of an iTBS modulated virtual reality challenge including participants with spider phobia. Biol Psychol. 2015 Dec;112:66-76. doi: 10.1016/j.biopsycho.2015.10.003. Epub 2015 Oct 22. — View Citation
Paes F, Baczynski T, Novaes F, Marinho T, Arias-Carrión O, Budde H, Sack AT, Huston JP, Almada LF, Carta M, Silva AC, Nardi AE, Machado S. Repetitive Transcranial Magnetic Stimulation (rTMS) to Treat Social Anxiety Disorder: Case Reports and a Review of the Literature. Clin Pract Epidemiol Ment Health. 2013 Oct 31;9:180-8. doi: 10.2174/1745017901309010180. eCollection 2013. — View Citation
Rossi S, Hallett M, Rossini PM, Pascual-Leone A; Safety of TMS Consensus Group. Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol. 2009 Dec;120(12):2008-2039. doi: 10.1016/j.clinph.2009.08.016. Epub 2009 Oct 14. Review. — View Citation
Suarez-Jimenez B, Bisby JA, Horner AJ, King JA, Pine DS, Burgess N. Linked networks for learning and expressing location-specific threat. Proc Natl Acad Sci U S A. 2018 Jan 30;115(5):E1032-E1040. doi: 10.1073/pnas.1714691115. Epub 2018 Jan 11. — View Citation
Szymanski J, O'Donohue W. Fear of Spiders Questionnaire. J Behav Ther Exp Psychiatry. 1995 Mar;26(1):31-4. — View Citation
Thayer JF, Ahs F, Fredrikson M, Sollers JJ 3rd, Wager TD. A meta-analysis of heart rate variability and neuroimaging studies: implications for heart rate variability as a marker of stress and health. Neurosci Biobehav Rev. 2012 Feb;36(2):747-56. doi: 10.1016/j.neubiorev.2011.11.009. Epub 2011 Dec 8. Review. — View Citation
Tomasino B, Fink GR, Sparing R, Dafotakis M, Weiss PH. Action verbs and the primary motor cortex: a comparative TMS study of silent reading, frequency judgments, and motor imagery. Neuropsychologia. 2008;46(7):1915-26. doi: 10.1016/j.neuropsychologia.2008.01.015. Epub 2008 Feb 2. — View Citation
Williams LM, Phillips ML, Brammer MJ, Skerrett D, Lagopoulos J, Rennie C, Bahramali H, Olivieri G, David AS, Peduto A, Gordon E. Arousal dissociates amygdala and hippocampal fear responses: evidence from simultaneous fMRI and skin conductance recording. Neuroimage. 2001 Nov;14(5):1070-9. — View Citation
* Note: There are 25 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Pain Score | The average post-treatment pain score as defined by the short-form 15-item McGill pain scale (scored from 0 to 45, with a higher score indicating a greater degree of pain, and a lower score indicating less pain). Each individual subject's average score was calculated by averaging his/her respective scores collected after each of the three TMS sessions. Each group's average score was calculated by averaging the average pain scores of each subject. | Days 1, 2, and 3 (after each TMS treatment) | |
Other | Group Assignment Conjecture | After completion of all other study-related activities and questionnaires (i.e. after completing post-treatment SPQ, FOS, and BAT during the followup visit), subjects were asked to guess to which group they had been assigned after completing the study and before being unblinded by the PI. Raters were also asked to guess to which group each subject had been assigned. Chi-squared analyses were performed for both subjects and raters for each group to validate blinding. | Immediately following repeat behavioral approach testing (i.e. the very last activity of the final/4th/followup visit). | |
Primary | 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 | |
Primary | 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 | |
Primary | 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 | Behavioral Approach Test, Change in Skin Conductance | The difference between the change in skin conductance measured during each step of the pre- and post-treatment behavioral approach tests (BATs). Differences were only compared in steps that subjects completed during both pre- and post-treatment BATs. | baseline and 1 week after treatment | |
Secondary | Change in Subjective Anticipatory Distress, Behavioral Approach Test | Changes in subjective pre-step anticipatory distress (reported 0-100) reported prior to each step during the behavioral approach test. Positive score indicates corresponding reduction in distress from pre- to post-treatment. | baseline and 1 week, difference reported | |
Secondary | Average Treatment Intensity Tolerated | The TMS treatment intensity tolerated by subjects in each group, averaged over the 3-day course of treatment for each subject. Ranges from 80-100% and is defined in reference to the subject's motor threshold. | Average tolerated intensity during TMS treatment sessions (days 1, 2, and 3 of treatment) | |
Secondary | Change in Subjective Maximum Distress, Behavioral Approach Test | Changes in subjective post-step maximum distress (reported 0-100) reported immediately following each step during the behavioral approach test. Positive change in score represents a corresponding reduction in relative distress. | baseline and 1 week, change in scores from pre to post reported |
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT04977544 -
Virtual Reality Exposure Therapy in the Intensive Treatment of Social Anxiety Disorder
|
N/A | |
Completed |
NCT03658252 -
Efficacy of Targeted Intervention for Topical Steroid Phobia.
|
N/A | |
Completed |
NCT03655262 -
Treating Phobia With Multivoxel Neuro-reinforcement
|
N/A | |
Completed |
NCT00451750 -
Cortisol in the Treatment of Phobias
|
N/A | |
Completed |
NCT04782570 -
Psychotherapy of Anxiety Disorders With Noninvasive Brain Stimulation - Using Virtual Reality
|
N/A | |
Not yet recruiting |
NCT06420557 -
Unconscious Reduction of Fear Through Decoded Neuro-Reinforcement
|
N/A | |
Recruiting |
NCT03528109 -
Improving Access to Child Anxiety Treatment
|
N/A | |
Not yet recruiting |
NCT03813823 -
Biobehavioral Correlates of Acute Phobic Fear
|
||
Completed |
NCT02810171 -
Dimensional Brain Behavior Predictors of CBT Outcomes in Pediatric Anxiety
|
N/A | |
Completed |
NCT02223767 -
TMS Augmented Exposure Therapy
|
N/A | |
Recruiting |
NCT03498599 -
Neuroimaging of Pavlovian Fear Conditioning Processes in Patients With Pathological Anxiety
|
N/A |