A triple-blinded placebo-controlled randomized clinical trial was performed with approval from the institutional research board/research ethics committee (IRB process number 2366732). The IRB approval was conducted through the UNINOVE University (Brazil). Informed consent was obtained (signed form) from all subjects prior to enrollment in this study. The study was conducted at the Laboratory of Phototherapy and Innovative Technologies in Health, between January and June of 2018. 80 subjects participated in this study in 2 groups of 40 subjects each. Human subject recruitment had the following inclusion and exclusion criteria:

Subjects who Satisfied any of the Following criteria were excluded from participation in this study:

previously hospitalized for a mental health condition.

history of traumatic brain injury or migraines.

diagnosed with post-traumatic stress disorder (PTSD) or with dissociative identity disorder.

diagnosed with a chronic pain disease, including chronic fatigue syndrome, fibromyalgia, endometriosis, inflammatory bowel disease, interstitial cystitis or diabetic neuropathic pain.

diagnosed with a serious mental health illness, such as dementia or schizophrenia,

any psychiatric hospitalization in the past two years,

diagnosed with a developmental disability or cognitive impairment,

participated in a clinical study or other type of clinical research in the past 30 days.

Subjects were randomized into two groups: a treatment group and a control (placebo) group with 40 subjects per group. Subjects were allocated to one of the two groups via variable block randomization with varying block sizes of two and four used at random to minimize the likelihood of predicting the next treatment group assignment. Randomization was performed using an automated computerized sequence methodology, which insures that the methodology and the sequence were concealed from the investigator and the subjects. Blinding of investigator to subject/group was insured by the following steps:

Each computer-generated randomization sequence was unique and was, therefore, not be able to be replicated.

Randomization occurred to either Procedure Group A or Procedure Group B instead of treatment or placebo group to conceal their identity.

Only the study Sponsor knew which assignment (Procedure Group A or B) corresponded to the TouchPoints™ devices and which one corresponded to the mock placebo device. The Sponsor did not reveal this information to any source (investigators, subjects, study monitors, or study analysts) until the final data analysis was completed.

Both the TouchPoints™ devices and the mock (placebo) devices were visually identical in appearance with the only difference being the lack of tactile response in the placebo devices.

Two metrics of stress were measured in each subject: a subjective rating of the level of emotional stress, and the level of salivary cortisol, a hormone whose release is associated with psychosocial stress 2122. Measurement for both metrics were taken at three time points for each subject: baseline (pre-treatment), immediately following completion of the TSST, and after 20 minutes of rest following the completion of the TSST. A 20-minute rest period was chosen for one of the timepoints because previous studies looking at the effect of meditation or relaxation techniques on stress hormones showed that the greatest drop in cortisol levels occurred after 20 minutes 232425. Moreover, since cortisol is stable in saliva, it can be collected at discrete time points to look for a time-dependent response 21.

Salivary cortisol samples were all collected daily between 11AM and 1PM to minimize Circadian variations 22. The amount of salivary cortisol in a sample was measured using a competitive immunoassay. The cortisol in the saliva competes with antibody binding sites on a test strip with cortisol conjugated with horseradish peroxidase. After incubation, the unbound cortisol is washed away, and a developing solution is added which reacts with horseradish peroxidase to produce a visual color. The amount of salivary cortisol is can be then calculated from a spectrophotometer reading of the developed test strip and is inversely proportional to the amount of cortisol conjugate present (optical density).

For the subjective stress rating, subjects were asked to rate their stress and anxiety on a scale ranging from 0 to 10, with 0 being no anxiety and 10 being the worst anxiety ever. All measurements were collected by an assessor who was not aware of the group assignment of each subject.

For each subject randomly divided into two groups (control versus treatment), according to the method described above, the following group-specific interventions were performed:

All statistical analysis was performed using the IBM Statistical Package for the Social Sciences (SPSS) 25.0 26. The intention-to-treat analysis was performed a priori. The researcher who performed the statistical analyses was blinded to the results of the randomization of subjects to the two groups. Data were first assessed for a normal (Gaussian) distribution using the Shapiro-Wilk test. Group results (i.e., subjective stress ratings, salivary cortisol levels) were expressed as a mean and standard deviation. A two-way ANOVA test was then used, followed by a Bonferroni post hoc test, to assess the statistical significance of these group results. The significance threshold was set at p < 0.05. Results of the two-way ANOVA were presented as mean and standard error of the mean (SEM).

Eighty healthy, male subjects were recruited and completed all procedures with no dropouts. The average age of 26.21 years ( 5.38 years). Table 1 lists the group mean and standard deviation (SD) for each of the chosen metrics (subjective stress rating (0-10 scale); salivary cortisol level) evaluated at each of the three time points in this study: baseline (prior to start of TSST); immediately following completion of TSST; after 20 minutes of rest following completion of TSST. There were no statistically significant group differences in the baseline (initial) measurements for either metric.

However, the results showed that the application of BLAST using TouchPoints™ significantly decreased the subject’s subjective stress level, when evaluated immediately following the completion of the TSST and after 20 minutes of rest following the completion of the TSST (Figure 1).

Results of the salivary cortisol levels did not reveal any statistically significant difference between the two groups (p > 0.05) at the initial time point. However, analysis of the change in salivary cortisol levels revealed that the subjects in the treatment group had a statistically significant difference in salivary cortisol levels immediately following the completion of the TSST, and at 20 minutes following the completion of the TSST, as compared to placebo (Figure 2).

In this study, our results showed that treatment with bilateral alternating somatosensory stimulation resulted in a statistically significant reduction in both subjective and quantitative metrics of stress and anxiety, as compared to placebo, assessed in subjects undergoing the TSST both immediately following the completion of the test and after 20 minutes of rest following the completion of the test. This suggests that this technique was effectively reducing stress during the active portion of the TSST and that this effect persisted following the TSST. This agrees with previous work which supports a role for bilateral alternating somatosensory information and EMDR in attenuating the stress response and returning stress induced reactions back to baseline. The statistically significant reduction in subjective stress ratings following treatment with BLAST agrees with a previous study by our group showing significant reductions in subjective ratings of both physical and psychological stress following 30 seconds of treatment with BLAST as compared to their baseline 18. It also supports several studies which have shown a beneficial effect of EMDR-based treatment on patients with high levels of anxiety 131527. The significant reduction in salivary cortisol levels in the treatment group as compared to the control group also is consistent with these results but, as a more quantitative and objective metric of the stress response 22, provides a novel and compelling additional support for the benefit of BLAST in attenuating the stress response. As with the subjective stress ratings in these subjects, there were no statistically significant differences between the two groups at the initial assessment. However, there was a statistically significant (p < 0.05) difference seen immediately following the TSST and after a twenty-minute rest following the TSST, when compared to the placebo group (p < 0.0001). A graph comparing the time course of the salivary cortisol levels between the two groups revealed a noticeable downward trending of the salivary cortisol levels in the treatment group that was not present in the controls. This may indicate a beneficial effect of bilateral alternating somatosensory stimulation in stabilizing cortisol levels and returning subjects to a normal baseline after a stress-induced response 22.