Healthy Adults
Conditions
Keywords
Post-traumatic stress, rTMS, randomized controlled trial, repetitive transcranial magnetic stimulation, transcranial magnetic stimulation, TMS
Brief summary
The goal of this clinical trial is to learn if a combined treatment using repetitive transcranial magnetic stimulation (rTMS) and expressive writing works to reduce symptoms of post-traumatic stress in adults. It will also study how safe this treatment is and whether the timing of rTMS changes how well it works. The main questions it aims to answer are: * Does this combined treatment lower symptoms of post-traumatic stress? * Does it work better when rTMS is given before or after expressive writing? Researchers will compare three groups to see which approach works best: * rTMS given before expressive writing * rTMS given after expressive writing * Sham stimulation (a look-alike procedure that does not provide real stimulation) Participants will: * Take part in sessions that include expressive writing about emotional experiences * Receive either real rTMS or sham stimulation * Complete questionnaires about post-traumatic stress, anxiety, depression, and mood * Have their heart rate and skin responses measured during the sessions * Be assessed before the study, after the sessions, and one month later This study includes adults aged 18 to 65 who have experienced at least one traumatic or highly stressful event and report symptoms of post-traumatic stress.
Detailed description
Objective: To evaluate the efficacy and safety of a combined intervention consisting of repetitive transcranial magnetic stimulation (rTMS) and emotional re-experiencing through expressive writing, as well as to analyze the influence of the timing of rTMS application on clinical outcomes in adults with post-traumatic stress symptomatology. Design: A randomized controlled superiority trial with three parallel groups: (1) rTMS administered 10 minutes prior to emotional re-experiencing via expressive writing, (2) rTMS administered 10 minutes after emotional re-experiencing, and (3) sham stimulation with an equivalent temporal structure. Assessments will be conducted at baseline, post-intervention, and at one-month follow-up. Study setting: University Institute of Neurosciences (IUNE), University of La Laguna (ULL), located in San Cristóbal de La Laguna, Santa Cruz de Tenerife, Canary Islands, Spain. Participants: Community-dwelling adults aged 18 to 65 years, exposed to at least one traumatic or highly stressful event, presenting post-traumatic stress symptomatology defined by a score ≥ 24 on the Revised Impact of Event Scale (IES-R). A total sample size of 45 participants is anticipated, distributed across three groups of 15 participants each. Measures: Post-traumatic stress symptomatology will be assessed using the IES-R; anxiety symptoms using the GAD-7; and depressive symptoms using the PHQ-9. Affect will be assessed with the PANAS. Physiological arousal will be recorded via heart rate and skin conductance using a polygraph. rTMS will be delivered using a Magstim Rapid2 stimulator with a figure-of-eight coil, guided by BrainSight neuronavigation. Emotional re-experiencing will be induced through expressive writing. Outcomes: The primary outcome will be the change in post-traumatic stress symptomatology. Secondary outcomes will include safety, measured by the frequency and type of adverse events and serious adverse events; changes in anxiety and depressive symptomatology; and situational changes in affect and physiological arousal during expressive writing sessions. Data analysis: Baseline characteristics of each group will be presented in a descriptive table. Continuous variables will be summarized using means and standard deviations, whereas categorical variables will be reported as absolute and relative frequencies. Between-group differences at baseline will be explored using analysis of variance (ANOVA) for continuous variables and chi-square tests of independence for categorical variables. Assumptions of normality and homogeneity of variances will be assessed beforehand. When these assumptions are violated, non-parametric alternatives will be used, including the Kruskal-Wallis test for continuous variables and Fisher's exact test for categorical variables. Intervention effects will be analyzed using linear mixed-effects models and, as a complementary approach, repeated-measures ANOVA. Main effects of group (sequential 1, sequential 2, and sham) and time (baseline, post-intervention, and one-month follow-up), as well as the group × time interaction, will be examined for the primary outcome (post-traumatic stress symptomatology) and secondary outcomes (anxiety symptoms, depressive symptoms, and situational changes). Analyses will be conducted under both an intention-to-treat (ITT) and per-protocol (PP) framework. The ITT population will include all randomized participants who have received at least one rTMS session, consistent with previous research (Philip et al., 2019). The PP population will include participants who completed the assigned treatment without substantial protocol deviations. For ITT analyses, missing data will be handled using linear mixed-effects models estimated via maximum likelihood, allowing the use of all available data under the assumption that missingness is at random (MAR). If evidence suggests that missing data may depend on unobserved variables (not missing at random, NMAR), sensitivity analyses will be conducted using pattern-mixture models or selection models to assess the robustness of the findings. Subgroup analyses are not planned. Results will be reported in tables with descriptive statistics by group and time point. Effect sizes (Cohen's d and partial eta squared) will be reported along with 95% confidence intervals. The statistical significance threshold will be set at α = .05, with Bonferroni correction applied when appropriate for multiple comparisons. All analyses will be performed using R statistical software (R Core Team, 2025).
Interventions
DEVICERepetitive Transcranial Magnetic Stimulation
rTMS will be administered by an experienced technician using a figure-of-eight coil connected to a Magstim Rapid2 stimulator (Magstim, Whitland, Dyfed, United Kingdom). Target localization will be performed using stereotactic neuronavigation with the frameless BrainSight system (Rogue Research, Canada) and a Polaris infrared tracking system (Northern Digital, Canada). Before each session and for each participant, the motor hotspot and resting motor threshold (rMT) will be determined. The hotspot will be defined as the stimulation site over the left primary motor cortex that produces the strongest and most consistent motor-evoked potentials in the first dorsal interosseous muscle, recorded via electromyography using a Biopac MP-35 system. The resting motor threshold will be defined as the minimum stimulation intensity capable of eliciting at least five small-amplitude motor responses out of ten stimuli applied to the relaxed muscle. The rTMS intensity will be individually adjusted
BEHAVIORALExpressive writing
Emotional re-experiencing will be induced through expressive writing. Participants will write for 15 minutes once per week about the thoughts and emotions associated with their traumatic or highly stressful experiences throughout the treatment period (Pennebaker \& Chung, 2011).
DEVICESham rTMS
Sham stimulation will be delivered using a placebo coil that reproduces the acoustic and procedural characteristics of rTMS without producing effective cortical stimulation.
Sponsors
Servicio Canario de Salud
University of La Laguna
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
Participants will remain blinded to their experimental condition through the use of sham rTMS as the control intervention. In addition, the researchers responsible for participant selection, clinical assessment, and administration of the expressive writing task will not have access to the randomization sequence or group allocation, thereby maintaining participant and assessor blinding throughout the study. Participants will be instructed not to disclose information about the rTMS sessions, and assessors will avoid asking about sensations or details related to the stimulation. An independent statistician, not involved in data analysis, will generate the randomization sequence. The trial statistician conducting the analysis will remain blinded to treatment allocation until the database is locked and analysis is complete.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Be between 18 and 65 years of age. * Have experienced at least one traumatic or highly stressful event, regardless of how much time has passed since the event occurred. * Present a score ≥ 24 on the Revised Impact of Event Scale (IES-R). * Have post-traumatic stress symptoms that are not better explained by another clinical condition or mental disorder.
Exclusion criteria
* History of epilepsy, seizures, or convulsions. * Presence of intracranial or cranial metal incompatible with rTMS. * History of severe traumatic brain injury. * Pregnancy or reasonable possibility of pregnancy. * Cochlear implants or internal pulse generators. * Use of medication that lowers the seizure threshold. * Current suicidal ideation or behaviour, or recent suicidal ideation within the past month. * Other medical or psychiatric conditions that contraindicate the use of rTMS. * Any condition that prevents participation in any of the study interventions. * Currently receiving psychological and/or pharmacological treatment for PTSD, acute stress, or another disorder that could account for post-traumatic stress symptoms. * Failure to provide written informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Post-traumatic stress symptoms | Assessment at baseline, immediately after treatment and one month follow-up | Post-traumatic stress symptomatology will be assessed using the Revised Impact of Event Scale (IES-R), a 22-item self-report instrument designed to measure subjective distress associated with traumatic or highly stressful events. The scale evaluates three core dimensions: intrusion, avoidance, and hyperarousal. In the present study, the IES-R will be used both to quantify the severity of post-traumatic stress symptoms and to establish eligibility criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events | Through study completion, an average of 2 months | Safety will be described by the number of participants who experience adverse events (AEs) and serious adverse events (SAEs), as well as by the total number of AEs and SAEs observed. An adverse event is defined as any undesirable experience associated with the use of a medical product in a participant. A serious adverse event, according to the U.S. Food and Drug Administration (FDA), refers to any undesirable experience associated with a medical treatment that results in death, is life-threatening, requires hospitalization, leads to disability or permanent damage, necessitates intervention to prevent further harm, or results in any other significant medical consequence. |
| Anxiety | Assessment at baseline, immediately after treatment and one month follow-up | Anxiety symptomatology will be assessed using the Generalized Anxiety Disorder-7 questionnaire (GAD-7). The GAD-7 is a brief 7-item self-report scale designed to evaluate the severity of generalized anxiety symptoms. |
| Depression | Assessment at baseline, immediately after treatment and one month follow-up | Depressive symptomatology will be assessed using the Patient Health Questionnaire-9 (PHQ-9). The PHQ-9 is a 9-item self-report measure designed to evaluate the severity of depressive symptoms. |
| Positive and negative affect | Assessment immediately after every expressive writing session | Affect will be assessed using the Positive and Negative Affect Schedule (PANAS). The PANAS is a 20-item self-report scale composed of two 10-item subscales that measure positive affect and negative affect, respectively. |
| Physiological arousal | From start to end of every expressive writing session | Physiological arousal will be indexed by heart rate and skin conductance, which will be recorded using a polygraph. |
Countries
Spain
Contacts
CONTACTLilisbeth Perestelo-Pérez, Doctor in Psychology
CONTACTWenceslao Peñate-Castro, Doctor in Psychology
Outcome results
None listed