Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03840369
Other study ID # REB18-1976
Secondary ID
Status Completed
Phase N/A
First received
Last updated
Start date June 1, 2020
Est. completion date March 18, 2022

Study information

Verified date May 2022
Source University of Calgary
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

In Canada, the prevalence of PTSD is approximately 12%, similar to Canadian military personnel. Current treatments for PTSD are limited in efficacy and durability - indicating a dire need for novel interventions in this population. Transcranial magnetic stimulation (TMS) has a high degree of safety and has been studied as an intervention for many mental health and neurological conditions; even showing initial promise for PTSD. We propose to study this further in a randomized sham controlled trial of TMS for PTSD.


Description:

In Canada, the prevalence of PTSD is approximately 12%, similar to Canadian military personnel. However, a 2002 study of members of Canadian Armed Forces found there was a striking positive correlation between the number of missions taken by the regular/reserve force and increase risk of developing PTSD, suggesting a dire need for further treatment options. Transcranial magnetic stimulation (TMS), a neuromodulation technique applied to the brain, has been studied as a treatment that has the potential to improve symptoms in a variety of neurological/mental health conditions. TMS is a safe and non-invasive technique that applies an electrical current to the brain to induce neuronal depolarization, changing regional brain function with the goal of improving neurological/psychiatric symptoms. Although multiple studies using TMS have suggested it as an efficacious treatment option for PTSD, clear knowledge gaps exist that prevent it from becoming evidence-based clinical care. A recent meta-analysis on TMS and PTSD found that no study has examined the difference between genders, and recommended that further studies with larger sample sizes, equal male and female participants, and more stringent study designs were required. Our study is novel and seeks to bridge the gap from research to clinical care by completing a study investigating repetitive TMS (rTMS) treatment for PTSD that recruits a large sample size, uses a randomized controlled clinical trial with a sham lead-in, and follows a stringent TMS protocol with equal sex participants. Not all individuals with PTSD respond to TMS treatment, and no study to date has explored what biomarkers may predict TMS responders in the PTSD population. Previous studies propose glutamate, BDNF and glutamatergic changes on MR spectroscopy may be altered in other mental health illnesses, which suggests they may be useful biomarkers of TMS response in PTSD. Therefore, this study will be the first of its kind to develop predictive biomarkers of response by sampling serum BDNF, glutamate, and glutamatergic changes in MR spectroscopy pre- and post rTMS treatment, in patients with PTSD that respond to TMS compared to those that do not. Recent studies have shown single-pulse TMS is beneficial for some individuals with chronic PTSD, and emerging evidence suggests there are specific phenotypes within PTSD that may require different TMS protocols. A recent study by Etkin et al. explored whether there were multiple phenotypes within chronic PTSD that would explain treatment responses. They found individuals with PTSD that scored significantly lower on verbal memory tasks (LVMS) (list repetition) had significantly impaired functional connectivity in the brain's ventral attention network (VAN) compared to patients with PTSD that had normal scores (NVMS). This suggests there may be a subgroup of patients with PTSD that would respond better to TMS in the right dorsal medial prefrontal cortex (DMPFC) (corresponding to the VAN) than to the right dorsal lateral prefrontal cortex (DLPFC).


Recruitment information / eligibility

Status Completed
Enrollment 25
Est. completion date March 18, 2022
Est. primary completion date February 18, 2022
Accepts healthy volunteers No
Gender All
Age group 18 Years to 65 Years
Eligibility Inclusion Criteria: 1. Adult participants represent a typically developing nervous system as a more reliable target for this stage of research. 2. The presence of a PTSD diagnosis made by a physician will ensure participants are experiencing significant symptomatology and may benefit from treatment. 3. The cutoff score on the PCL-5 will ensure that participants are experiencing similar levels of symptoms to each other. 4. Need to have tried at least two types of treatment in the past Exclusion Criteria: 1. Significant past medical history including seizures, stroke, severe traumatic brain injury, or central nervous system cancers may interfere with our evaluation of treatment outcome and will be criteria for exclusion. 2. Metal in head/neck/eye is a contraindication to safety in the MRI scanner and TMS protocol. 3. Women who are pregnant will not be included in the study due to potential risk of seizure during TMS. To determine if a patient is pregnant we will ask when their last menstrual cycle occurred. If there is a possibility of pregnancy, we will ask the participant to follow-up with their family doctor to confirm. We will then ask the participant to provide a written note from their treating practitioner stating they are not pregnant. 4. Active suicidality 5. Wellbutrin or benzodiazepine intake of more than 200mg/day, or more than 15 mg of Zopiclone per day as these medications lower seizure threshold 6. Trauma experienced less than a year ago and/or trauma experienced only as a child 7. Drug and/or alcohol abuse within the last 3 months (diagnosed by Canadian guidelines) 8. Diagnosed schizophrenia, untreated bipolar disorder, or psychosis

Study Design


Related Conditions & MeSH terms


Intervention

Device:
Repetitive Transcranial Magnetic Stimulation to Right Dorsolateral Prefrontal Cortex
Transcranial magnetic stimulation (TMS) works by delivering a magnetic pulse to a focal brain region. TMS has a high degree of safety and has been studied as an intervention for many mental health and neurological conditions. Repetitive TMS (rTMS) delivers pulses at a set time interval in order to modulate neural activity in that region.
Sham Repetitive Transcranial Magnetic Stimulation
The sham TMS coil will make a similar sound to the real rTMS coil, but will not deliver a magnetic pulse. This is a no-treatment device.
Repetitive Transcranial Magnetic Stimulation to Right Dorsomedial Prefrontal Cortex
Transcranial magnetic stimulation (TMS) works by delivering a magnetic pulse to a focal brain region. TMS has a high degree of safety and has been studied as an intervention for many mental health and neurological conditions. Repetitive TMS (rTMS) delivers pulses at a set time interval in order to modulate neural activity in that region.

Locations

Country Name City State
Canada Foothill Medical Centre Calgary Alberta

Sponsors (2)

Lead Sponsor Collaborator
University of Calgary Defence Research and Development Canada

Country where clinical trial is conducted

Canada, 

References & Publications (25)

Berlim MT, Van Den Eynde F. Repetitive transcranial magnetic stimulation over the dorsolateral prefrontal cortex for treating posttraumatic stress disorder: an exploratory meta-analysis of randomized, double-blind and sham-controlled trials. Can J Psychiatry. 2014 Sep;59(9):487-96. — View Citation

Cirillo P, Gold AK, Nardi AE, Ornelas AC, Nierenberg AA, Camprodon J, Kinrys G. Transcranial magnetic stimulation in anxiety and trauma-related disorders: A systematic review and meta-analysis. Brain Behav. 2019 Jun;9(6):e01284. doi: 10.1002/brb3.1284. Epub 2019 May 7. — View Citation

Enokibara M, Trevizol A, Shiozawa P, Cordeiro Q. Establishing an effective TMS protocol for craving in substance addiction: Is it possible? Am J Addict. 2016 Jan;25(1):28-30. doi: 10.1111/ajad.12309. Epub 2015 Dec 21. Review. — View Citation

Etkin A, Maron-Katz A, Wu W, Fonzo GA, Huemer J, Vértes PE, Patenaude B, Richiardi J, Goodkind MS, Keller CJ, Ramos-Cejudo J, Zaiko YV, Peng KK, Shpigel E, Longwell P, Toll RT, Thompson A, Zack S, Gonzalez B, Edelstein R, Chen J, Akingbade I, Weiss E, Hart R, Mann S, Durkin K, Baete SH, Boada FE, Genfi A, Autea J, Newman J, Oathes DJ, Lindley SE, Abu-Amara D, Arnow BA, Crossley N, Hallmayer J, Fossati S, Rothbaum BO, Marmar CR, Bullmore ET, O'Hara R. Using fMRI connectivity to define a treatment-resistant form of post-traumatic stress disorder. Sci Transl Med. 2019 Apr 3;11(486). pii: eaal3236. doi: 10.1126/scitranslmed.aal3236. — View Citation

Fryml LD, Sahlem G, Fox J, Short EB. The role of rTMS for patients with severe PTSD and depression. Evid Based Ment Health. 2018 Feb;21(1):39-40. doi: 10.1136/eb-2017-102819. Epub 2018 Jan 5. — View Citation

Hendrikse J, Kandola A, Coxon J, Rogasch N, Yücel M. Combining aerobic exercise and repetitive transcranial magnetic stimulation to improve brain function in health and disease. Neurosci Biobehav Rev. 2017 Dec;83:11-20. doi: 10.1016/j.neubiorev.2017.09.023. Epub 2017 Sep 23. Review. — View Citation

Kalita J, Laskar S, Bhoi SK, Misra UK. Efficacy of single versus three sessions of high rate repetitive transcranial magnetic stimulation in chronic migraine and tension-type headache. J Neurol. 2016 Nov;263(11):2238-2246. Epub 2016 Aug 19. — View Citation

Kobayashi M, Pascual-Leone A. Transcranial magnetic stimulation in neurology. Lancet Neurol. 2003 Mar;2(3):145-56. Review. — View Citation

Kozel FA, Motes MA, Didehbani N, DeLaRosa B, Bass C, Schraufnagel CD, Jones P, Morgan CR, Spence JS, Kraut MA, Hart J Jr. Repetitive TMS to augment cognitive processing therapy in combat veterans of recent conflicts with PTSD: A randomized clinical trial. J Affect Disord. 2018 Mar 15;229:506-514. doi: 10.1016/j.jad.2017.12.046. Epub 2017 Dec 28. — View Citation

Kozel FA. Clinical Repetitive Transcranial Magnetic Stimulation for Posttraumatic Stress Disorder, Generalized Anxiety Disorder, and Bipolar Disorder. Psychiatr Clin North Am. 2018 Sep;41(3):433-446. doi: 10.1016/j.psc.2018.04.007. Review. — View Citation

Lee JC, Blumberger DM, Fitzgerald PB, Daskalakis ZJ, Levinson AJ. The role of transcranial magnetic stimulation in treatment-resistant depression: a review. Curr Pharm Des. 2012;18(36):5846-52. Review. — View Citation

Lewis CP, Port JD, Frye MA, Vande Voort JL, Ameis SH, Husain MM, Daskalakis ZJ, Croarkin PE. An Exploratory Study of Spectroscopic Glutamatergic Correlates of Cortical Excitability in Depressed Adolescents. Front Neural Circuits. 2016 Nov 29;10:98. eCollection 2016. — View Citation

Liu G, Feng D, Wang J, Zhang H, Peng Z, Cai M, Yang J, Zhang R, Wang H, Wu S, Tan Q. rTMS Ameliorates PTSD Symptoms in Rats by Enhancing Glutamate Transmission and Synaptic Plasticity in the ACC via the PTEN/Akt Signalling Pathway. Mol Neurobiol. 2018 May;55(5):3946-3958. doi: 10.1007/s12035-017-0602-7. Epub 2017 May 26. — View Citation

Moshe H, Gal R, Barnea-Ygael N, Gulevsky T, Alyagon U, Zangen A. Prelimbic Stimulation Ameliorates Depressive-Like Behaviors and Increases Regional BDNF Expression in a Novel Drug-Resistant Animal Model of Depression. Brain Stimul. 2016 Mar-Apr;9(2):243-50. doi: 10.1016/j.brs.2015.10.009. Epub 2015 Nov 10. — View Citation

Nam DH, Pae CU, Chae JH. Low-frequency, Repetitive Transcranial Magnetic Stimulation for the Treatment of Patients with Posttraumatic Stress Disorder: a Double-blind, Sham-controlled Study. Clin Psychopharmacol Neurosci. 2013 Aug;11(2):96-102. doi: 10.9758/cpn.2013.11.2.96. Epub 2013 Aug 26. — View Citation

Novakovic V, Sher L, Lapidus KA, Mindes J, A Golier J, Yehuda R. Brain stimulation in posttraumatic stress disorder. Eur J Psychotraumatol. 2011;2. doi: 10.3402/ejpt.v2i0.5609. Epub 2011 Oct 17. — View Citation

Osuch EA, Benson BE, Luckenbaugh DA, Geraci M, Post RM, McCann U. Repetitive TMS combined with exposure therapy for PTSD: a preliminary study. J Anxiety Disord. 2009 Jan;23(1):54-9. doi: 10.1016/j.janxdis.2008.03.015. Epub 2008 Mar 28. — View Citation

Oznur T, Akarsu S, Celik C, Bolu A, Ozdemir B, Akcay BD, Ozselek S, Bozkurt A, Ozmenler KN. Is transcranial magnetic stimulation effective in treatment-resistant combat related posttraumatic stress disorder? Neurosciences (Riyadh). 2014 Jan;19(1):29-32. — View Citation

Philip NS, Ridout SJ, Albright SE, Sanchez G, Carpenter LL. 5-Hz Transcranial Magnetic Stimulation for Comorbid Posttraumatic Stress Disorder and Major Depression. J Trauma Stress. 2016 Feb;29(1):93-6. doi: 10.1002/jts.22065. Epub 2016 Jan 7. — View Citation

Pohar R, Farrah K. Repetitive Transcranial Magnetic Stimulation for Patients with Depression: A Review of Clinical Effectiveness, Cost-Effectiveness and Guidelines - An Update [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2019 Jun 28. Available from http://www.ncbi.nlm.nih.gov/books/NBK545105/ — View Citation

Pradhan B, Kluewer D'Amico J, Makani R, Parikh T. Nonconventional interventions for chronic post-traumatic stress disorder: Ketamine, repetitive trans-cranial magnetic stimulation (rTMS), and alternative approaches. J Trauma Dissociation. 2016;17(1):35-54. doi: 10.1080/15299732.2015.1046101. Epub 2015 Jul 10. Review. — View Citation

Vucic S, Kiernan MC. Transcranial Magnetic Stimulation for the Assessment of Neurodegenerative Disease. Neurotherapeutics. 2017 Jan;14(1):91-106. doi: 10.1007/s13311-016-0487-6. Review. — View Citation

Wang HN, Bai YH, Chen YC, Zhang RG, Wang HH, Zhang YH, Gan JL, Peng ZW, Tan QR. Repetitive transcranial magnetic stimulation ameliorates anxiety-like behavior and impaired sensorimotor gating in a rat model of post-traumatic stress disorder. PLoS One. 2015 Feb 6;10(2):e0117189. doi: 10.1371/journal.pone.0117189. eCollection 2015. — View Citation

Watts BV, Landon B, Groft A, Young-Xu Y. A sham controlled study of repetitive transcranial magnetic stimulation for posttraumatic stress disorder. Brain Stimul. 2012 Jan;5(1):38-43. doi: 10.1016/j.brs.2011.02.002. Epub 2011 Mar 3. — View Citation

Yan T, Xie Q, Zheng Z, Zou K, Wang L. Different frequency repetitive transcranial magnetic stimulation (rTMS) for posttraumatic stress disorder (PTSD): A systematic review and meta-analysis. J Psychiatr Res. 2017 Jun;89:125-135. doi: 10.1016/j.jpsychires.2017.02.021. Epub 2017 Feb 27. Review. — View Citation

* Note: There are 25 references in allClick here to view all references

Outcome

Type Measure Description Time frame Safety issue
Other Effect of rTMS on Quality of Life After Brain Injury survey (QOLIBRI), headaches, anxiety and depression in individuals with PTSD To determine if quality of life (QOLIBRI), including headaches, anxiety, and depression also improve with the rTMS treatment in individuals suffering with PTSD Change in QOLIBRI score at the pre-treatment appointment compared with 1 week, upon study completion, and 4 weeks post treatment.
Primary Effect of 20-session rTMS Intervention to the DMPFC versus DLPFC on PCL Overall Score, Stratified by Verbal Memory Task Scores To determine whether patients with PTSD_LVMS have a greater response to a 20-day low frequency rTMS treatment protocol of the right DMPFC compared to the DLPFC, and if patients with PTSD_NVMS respond better to a 20-day low frequency TMS treatment protocol of the right DLPFC compared to the DMPFC as measured by the clinician administered PTSD scale for DSM-5 (CAPS-5) in male and female participants (military personnel and civilians) at 4 weeks and 1 month post-treatment. Change in PCL-5 score at pre-treatment appointment, compared with the score at 1 week, upon study completion, and 4 weeks post-rTMS treatment.
Secondary Serum BDNF, Glutamate, Glutathione, and MR Spectroscopy pre and post rTMS intervention To determine if serum brain derived neurotrophic factor (BDNF), glutamate, glutathione, and MR spectroscopy imaging will predict rTMS response in individuals with PTSD compared to those that do not respond to rTMS treatment. Change in serum BDNF, glutamate, and glutathione at the pre-treatment appointment compared with 1 week into treatment and upon study completion.
See also
  Status Clinical Trial Phase
Recruiting NCT05620381 - Health and Sleep Assessment After the Strasbourg Attacks of December 11, 2018
Completed NCT02856412 - Improving Mind/Body Health and Functioning With Integrative Exercise N/A
Recruiting NCT05400200 - PTSD and Self-regulation: Coping, Emotional Regulation and Cognitive Control and Their Relationships to Symptom Management N/A
Not yet recruiting NCT06088303 - Enhancing PTSD Treatment Outcomes by Improving Patient-Provider Communication N/A
Not yet recruiting NCT03652922 - Propranolol Reactivation Mismatch (PRM) Treatment for PTSD Phase 4
Completed NCT02875912 - Prospective Evaluation of Family Care Rituals in the ICU N/A
Completed NCT01589575 - Anxiety and Depression in Relatives of Critically Ill Patients: Spouses Versus Other Close Relatives N/A
Completed NCT00990106 - Augmentation Trial of Prazosin for Post-Traumatic Stress Disorder (PTSD) N/A
Completed NCT01291368 - Sedation Influence on Delirium and Post-traumatic Stress-disorder as a Result of Hospitalization in Intensive Care N/A
Active, not recruiting NCT00657787 - Development of a Post-Traumatic Stress Disorder (PTSD) Population Registry for Veterans
Completed NCT00880152 - Mindfulness Based Stress Reduction for Posttraumatic Stress Disorder: A Pilot Study N/A
Completed NCT00835627 - Treatment Trial for Psychogenic Nonepileptic Seizures Phase 4
Completed NCT01365247 - Concurrent Treatment for Substance Dependent Individuals With Post-Traumatic Stress Disorder (PTSD) N/A
Completed NCT00514956 - Effect of Emotional Freedom Technique and Diaphragmatic Breathing on Post Traumatic Stress Disorder (PTSD) Phase 1
Completed NCT00419029 - Motivational Interviewing to Engage Operations Enduring Freedom and Iraqi Freedom (OEF/OIF) Veterans in Mental Health Treatment N/A
Completed NCT00333710 - Evaluating a Telehealth Treatment for Veterans With Hepatitis C and PTSD N/A
Completed NCT01120847 - Post Traumatic Stress Disorder (PTSD), Sleep Disordered Breathing And Genetics: Effects On Cognition
Completed NCT00069225 - Brain Structure and Function Before and After Treatment for Post-Traumatic Stress Disorder N/A
Completed NCT00055354 - Acupuncture for the Treatment of Post-Traumatic Stress Disorder (PTSD) N/A
Completed NCT00186212 - Alternative Support for Rural and Isolated Women in an HMO Phase 3

External Links