Clinical trial NCT03529981: Wearable Emotion Prosthetics for Post Traumatic Stress Disorder
Official title: Wearable Emotion Prosthetics for Post Traumatic Stress Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Health Behavior
Keywords: PTSD
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
First posted: 2018-05-21
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 58
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: randomized, controlled factorial within subject design
Primary purpose: BASIC_SCIENCE

Brief summary: Involuntary stress reactions including hyper-reactivity and dissociation are key diagnostic features of many psychiatric disorders, are difficult to treat, and predict poor outcomes in conventional and neurobehavioral interventions. Here, we evaluate the extent to which a novel intervention, Tuned Vibroacoustic Stimulation (TVS), capitalizing on a preserved neurocircuitry for sympathetic and parasympathetic system activity can be used to modify arousal responses, overriding otherwise prepotent negative stress reactions.

PTSD has been characterized by dysregulated responses to stress as a result of severe acute or chronic trauma resulting in significantly impaired functioning, quality of life, and morbidity/mortality. Physiologically, PTSD severity has been associated with elevated sympathetic tone and low heart rate variability suggesting that parasympathetic tone is suppressed. Lower heart rate variability specifically, as a measure of parasympathetic tone, is closely associated with impaired performance and resilience. In our first study (in review), we showed that in some individuals, TVS is associated with increased heart rate variability and performance under stress along with reduced subjective stress. These results suggest that TVS could provide some therapeutic benefit in PTSD.

N=100 individuals with mild-moderate PTSD (as assessed by PCL-5/CAP5), at least half of which are military Veterans, will be assessed physiologically during active interventions. Mechanisms of attentional focus on cognitive and emotional stimuli will be assessed. Participants will also have a real-world intervention to determine if TVS helps alleviate stress, symptoms, and medication burden in the real world when stress has been identified. Success will suggest a new intervention pathway for a traditionally treatment-resistant dimension of psychopathology.

Detailed description: This protocol will examine and elucidate a mechanistic model for tuned vibroacoustic stimulation (TVS), an exteroceptive cue that has been shown to reduce subjective and physiological indicators of stress and increase behavioral performance in healthy subjects. In this study, we will test whether TVS can reduce subjective and physiological signs of stress, improve performance, alleviate symptoms, and reduce medication burden in adults with post-traumatic stress disorder (PTSD). This protocol will also examine whether software that cues TVS in response to biological stress markers helps users detect, regulate, and develop long-term resilience to stress outside of the laboratory.

Aim 1: Examine how TVS alters calmness and stress markers. Our overall hypothesis is that TVS, in combination with some other task, increases performance on that task by decreasing stress and increasing emotion regulation.

Hypothesis 1: TVS during an attention task will lead to decreased GSR, increased HRV, and increases in prefrontal gamma and theta band EEG, along with improved behavioral performance on a focused attention, working memory and emotional information processing task. TVS will also reduce subjective stress levels.

Aim 2: Examine the extent to which software, which monitors real time biological stress markers of users, and in response, automatically signals wearable hardware to deliver TVS when user is stressed, will be able to help users detect, regulate, and develop long-term resilience to stress outside the laboratory for two weeks.

Hypothesis 2.1: Evaluate whether subjects with PTSD in the real world will use our software to detect and alert them of stress dynamically and if this is associated with stress regulation.

Hypothesis 2.2: Examine whether TVS is associated with stress regulation. Hypothesis 2.3: Examine whether TVS is associated with reduction in PTSD symptoms and, possibly, medication burden.

Over 39 million Americans suffer from excessive chronic stress, which can be psychologically and physically debilitating (Salleh, 2008). Untreated chronic stress plays a role in the development of major illnesses such as cardiovascular disease, obesity, anxiety and depression (Dallman et al., 2006; Swaab, Bao, \& Lucassen, 2005). Post-traumatic stress disorder (PTSD), is a severe mental illness that impacts millions of veterans and civilians nationwide. Existing treatments for chronic stress and PTSD are often ineffective, have adverse effects, and are prohibited by cost, time-commitment, and accessibility, resulting in high rates of substance abuse and suicide (Jonas et al., 2013; Watts et al., 2013). Stress in general, and PTSD more specifically, are characterized by hyper-reactivity in the sympathetic nervous system which is associated with increased arousal and vigilance, and compromised reactivity of the parasympathetic nervous system, which helps to regulate emotion and stress responses (Kibler, Tursich, Ma, Malcolm, \& Greenbarg, 2014; Lehrer \& Gevirtz, 2014).

PTSD has been characterized by dysregulated responses to stress as a result of severe acute or chronic trauma resulting in significantly impaired functioning, quality of life, and morbidity/mortality. Physiologically, PTSD severity has been associated with elevated sympathetic tone and low heart rate variability suggesting that parasympathetic tone is suppressed. HRV is widely used as a biomarker for the coordinated activity of the sympathetic and parasympathetic nervous symptom. A calmer, less stressful state is typically marked by increased HRV, likely attributed to respiration based parasympathetic stimulation (Grossman \& Taylor, 2007). GSR is also a reliable index for sweat gland activity and changes in activation level of the sympathetic nervous system, and GSR usually increases with higher levels of stress (Mohan, Sharma, \& Bijlani, 2011). EEG changes, such as elevated prefrontal gamma and theta, have also been associated with state of relaxed alertness. Our initial data (submitted) suggest that for some individuals, TVS can boost heart rate variability and performance under stress while reducing subjective stress. These results suggest that TVS could provide some therapeutic benefit in PTSD.

Large scientific literature supports the role of vibration in regulating stress physiology (Takahashi, Ohashi, \& Yokoyama, 2011; M. Uchikune, 2002; M. Uchikune, 2004). For example, slow whole-body vibration, in the 0.01 to 0.3 Hz range, is associated with increased ratings of pleasantness and increased parasympathetic tone (M. Uchikune, 2002; M. Uchikune, 2004). Stimulation at about 100 Hz has been shown to activate the posterior insula (Coghill et al., 1994) which is associated with increased attention to interoception, as promoted in many meditative traditions. Transcutaneous targets for the vibration frequencies have also been identified, including stellate ganglion and vagus nerve (Cipriano et al., 2014; Fang et al., 2016).

In this study, we will be testing the potential for TVS to increase well-being (subjective calmness, increased performance, and physiological reactivity) in the PTSD population. Positive results would suggest that reduction in symptomatology may be possible without effort, and in lieu of specific interventions with medications or psychotherapy. A wearable form of TVS technology will be examined in a real-world setting. We will use ambulatory assessment to detect physiological indications of stress unique to each user and to provide user-optimized TVS, examining whether it increases parasympathetic nervous system reactivity in response to stress, thus decreasing subjective stress just as a user's stress begins to increase.

Eligibility criteria: Inclusion Criteria:

* Male/female who are 18 - 58 years of age
* For PTSD participants, must meet current DSM-V criteria for PTSD based on the PCL-5 (Score \> 33) and MINI PTSD Scale (administered in lab).
* If taking psychoactive medications, must be on a stable regimen for 3 weeks or more.
* Must have a functioning smartphone with Apple iOS or Android

Exclusion Criteria:

* Refusal or inability to provide informed consent
* Current suicidal or homicidal ideation with intent and/or plan that, in the judgment of the investigator, should be the focus of treatment.
* Current or recent (within the last 8 weeks) physically aggressive behavior.
* Meets current DSM-V criteria for substance dependence ((serious substance use in DSM-V parlance, not in remission) except nicotine and caffeine), traumatic brain injury, bipolar affective disorder, schizophrenia or any psychotic disorder.
* Has unstable or serious medical illness, including history of stroke, epileptic disorder, or unstable cardiac disease, that would interfere with participation in treatment.
* Taking medications that could affect thinking which must be taken on the day of testing, or dependence on psychoactive drugs (prescription or non-prescription) that could affect thinking. That is, participants need to be able to think clearly to complete the proposed information processing tasks. And they need to be able to learn to be able to make use of the intervention. Examples of drugs which could affect performance on cognitive tasks or the administered physiological measures include beta-blockers, benzodiazepines, antipsychotics, stimulants (except for treatment of ADD/ADHD), narcotics, and anti--Parkinsonian drugs.
* Severe cognitive impairment or severe trauma
* Unable to comprehend or communicate in English, and unable to complete questionnaires written in English.
* Having any eye problems or difficulties in corrected vision or hearing, including poor color vision
* Having a North American Adult Reading Test (NAART) equivalent FSIQ \< 85
* Severe or poorly controlled concurrent medical disorders or require medication that could cause negative thinking

Specific Exclusions for acoustic vibration include:

-- Any electrical implant (pacemaker, vagus nerve stimulator, etc).

Primary outcomes:
measure: Change in symptom ratings from pre- to post-
timeFrame: Change in symptom ratings over the approximately two weeks of the acute intervention (pre- to post- assessment)
measure: Change in resting Heart Rate Variability (HRV) from pre- to post-
timeFrame: HRV will be measured during the entire study which is two weeks
Secondary outcomes:
measure: Change in Heart Rate Variability (HRV) during information processing tasks (composite)
timeFrame: HRV will be measured during the approximately 1 hour of information processing tasks, which will be administered approximately 2 weeks apart, at the pre- and post- intervention assessment visits.
measure: Galvanic skin response (GSR) during information processing tasks (composite)
timeFrame: GSR will be measured during the approximately 1 hour of information processing tasks, which will be administered approximately 2 weeks apart, at the pre- and post- intervention assessment visits.
measure: prefrontal gamma band EEG during information processing tasks (composite)
timeFrame: EEG will be measured during the approximately 1 hour of information processing tasks, which will be administered approximately 2 weeks apart, at the pre- and post- intervention assessment visits.
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: Western Psychiatric Institute and Clinic
state: Pennsylvania
Study officials:
affiliation: Western Psychiatric Institute and Clinic
name: Greg Siegle, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Brown KW, Ryan RM. The benefits of being present: mindfulness and its role in psychological well-being. J Pers Soc Psychol. 2003 Apr;84(4):822-48. doi: 10.1037/0022-3514.84.4.822.
citation: Carlson LE, Brown KW. Validation of the Mindful Attention Awareness Scale in a cancer population. J Psychosom Res. 2005 Jan;58(1):29-33. doi: 10.1016/j.jpsychores.2004.04.366.
citation: Cipriano G Jr, Neder JA, Umpierre D, Arena R, Vieira PJ, Chiappa AM, Ribeiro JP, Chiappa GR. Sympathetic ganglion transcutaneous electrical nerve stimulation after coronary artery bypass graft surgery improves femoral blood flow and exercise tolerance. J Appl Physiol (1985). 2014 Sep 15;117(6):633-8. doi: 10.1152/japplphysiol.00993.2013. Epub 2014 Aug 7.
citation: Coghill RC, Talbot JD, Evans AC, Meyer E, Gjedde A, Bushnell MC, Duncan GH. Distributed processing of pain and vibration by the human brain. J Neurosci. 1994 Jul;14(7):4095-108. doi: 10.1523/JNEUROSCI.14-07-04095.1994.
citation: Creswell JD. Mindfulness Interventions. Annu Rev Psychol. 2017 Jan 3;68:491-516. doi: 10.1146/annurev-psych-042716-051139. Epub 2016 Sep 28.
citation: Dallman MF, Pecoraro NC, La Fleur SE, Warne JP, Ginsberg AB, Akana SF, Laugero KC, Houshyar H, Strack AM, Bhatnagar S, Bell ME. Glucocorticoids, chronic stress, and obesity. Prog Brain Res. 2006;153:75-105. doi: 10.1016/S0079-6123(06)53004-3.
citation: Dittrich A. The standardized psychometric assessment of altered states of consciousness (ASCs) in humans. Pharmacopsychiatry. 1998 Jul;31 Suppl 2:80-4. doi: 10.1055/s-2007-979351.
citation: Fang J, Rong P, Hong Y, Fan Y, Liu J, Wang H, Zhang G, Chen X, Shi S, Wang L, Liu R, Hwang J, Li Z, Tao J, Wang Y, Zhu B, Kong J. Transcutaneous Vagus Nerve Stimulation Modulates Default Mode Network in Major Depressive Disorder. Biol Psychiatry. 2016 Feb 15;79(4):266-73. doi: 10.1016/j.biopsych.2015.03.025. Epub 2015 Apr 2.
citation: Fredrickson BL. The broaden-and-build theory of positive emotions. Philos Trans R Soc Lond B Biol Sci. 2004 Sep 29;359(1449):1367-78. doi: 10.1098/rstb.2004.1512.
citation: Fredrickson BL, Branigan C. Positive emotions broaden the scope of attention and thought-action repertoires. Cogn Emot. 2005 May 1;19(3):313-332. doi: 10.1080/02699930441000238.
citation: Fredrickson BL, Joiner T. Positive emotions trigger upward spirals toward emotional well-being. Psychol Sci. 2002 Mar;13(2):172-5. doi: 10.1111/1467-9280.00431.
citation: Fredrickson BL, Levenson RW. Positive Emotions Speed Recovery from the Cardiovascular Sequelae of Negative Emotions. Cogn Emot. 1998 Mar 1;12(2):191-220. doi: 10.1080/026999398379718.
citation: Fredrickson BL, Tugade MM, Waugh CE, Larkin GR. What good are positive emotions in crises? A prospective study of resilience and emotions following the terrorist attacks on the United States on September 11th, 2001. J Pers Soc Psychol. 2003 Feb;84(2):365-76. doi: 10.1037//0022-3514.84.2.365.
citation: Grossman P, Taylor EW. Toward understanding respiratory sinus arrhythmia: relations to cardiac vagal tone, evolution and biobehavioral functions. Biol Psychol. 2007 Feb;74(2):263-85. doi: 10.1016/j.biopsycho.2005.11.014. Epub 2006 Nov 1.
citation: Jonas DE, Cusack K, Forneris CA, Wilkins TM, Sonis J, Middleton JC, Feltner C, Meredith D, Cavanaugh J, Brownley KA, Olmsted KR, Greenblatt A, Weil A, Gaynes BN. Psychological and Pharmacological Treatments for Adults With Posttraumatic Stress Disorder (PTSD) [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2013 Apr. Report No.: 13-EHC011-EF. Available from http://www.ncbi.nlm.nih.gov/books/NBK137702/
citation: Kabat-Zinn J. An outpatient program in behavioral medicine for chronic pain patients based on the practice of mindfulness meditation: theoretical considerations and preliminary results. Gen Hosp Psychiatry. 1982 Apr;4(1):33-47. doi: 10.1016/0163-8343(82)90026-3.
citation: Kabat-Zinn J, Massion AO, Kristeller J, Peterson LG, Fletcher KE, Pbert L, Lenderking WR, Santorelli SF. Effectiveness of a meditation-based stress reduction program in the treatment of anxiety disorders. Am J Psychiatry. 1992 Jul;149(7):936-43. doi: 10.1176/ajp.149.7.936.
citation: Kibler JL, Tursich M, Ma M, Malcolm L, Greenbarg R. Metabolic, autonomic and immune markers for cardiovascular disease in posttraumatic stress disorder. World J Cardiol. 2014 Jun 26;6(6):455-61. doi: 10.4330/wjc.v6.i6.455.
citation: Kok BE, Coffey KA, Cohn MA, Catalino LI, Vacharkulksemsuk T, Algoe SB, Brantley M, Fredrickson BL. How positive emotions build physical health: perceived positive social connections account for the upward spiral between positive emotions and vagal tone. Psychol Sci. 2013 Jul 1;24(7):1123-32. doi: 10.1177/0956797612470827. Epub 2013 May 6.
citation: Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001 Sep;16(9):606-13. doi: 10.1046/j.1525-1497.2001.016009606.x.
citation: Lehrer PM, Gevirtz R. Heart rate variability biofeedback: how and why does it work? Front Psychol. 2014 Jul 21;5:756. doi: 10.3389/fpsyg.2014.00756. eCollection 2014.
citation: Lomas T, Ivtzan I, Fu CH. A systematic review of the neurophysiology of mindfulness on EEG oscillations. Neurosci Biobehav Rev. 2015 Oct;57:401-10. doi: 10.1016/j.neubiorev.2015.09.018. Epub 2015 Oct 9.
citation: Ludwig DS, Kabat-Zinn J. Mindfulness in medicine. JAMA. 2008 Sep 17;300(11):1350-2. doi: 10.1001/jama.300.11.1350. No abstract available.
citation: Mohan A, Sharma R, Bijlani RL. Effect of meditation on stress-induced changes in cognitive functions. J Altern Complement Med. 2011 Mar;17(3):207-12. doi: 10.1089/acm.2010.0142. Epub 2011 Mar 9.
citation: Ong AD, Bergeman CS, Bisconti TL, Wallace KA. Psychological resilience, positive emotions, and successful adaptation to stress in later life. J Pers Soc Psychol. 2006 Oct;91(4):730-49. doi: 10.1037/0022-3514.91.4.730.
citation: Salleh MR. Life event, stress and illness. Malays J Med Sci. 2008 Oct;15(4):9-18.
citation: Schofield TP, Creswell JD, Denson TF. Brief mindfulness induction reduces inattentional blindness. Conscious Cogn. 2015 Dec;37:63-70. doi: 10.1016/j.concog.2015.08.007. Epub 2015 Aug 28.
citation: Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, Hergueta T, Baker R, Dunbar GC. The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry. 1998;59 Suppl 20:22-33;quiz 34-57.
citation: Swaab DF, Bao AM, Lucassen PJ. The stress system in the human brain in depression and neurodegeneration. Ageing Res Rev. 2005 May;4(2):141-94. doi: 10.1016/j.arr.2005.03.003.
citation: Takahashi I, Ohashi H, Yokoyama K. Optimum arousal level preservation system using biosignals. J Hum Ergol (Tokyo). 2011 Dec;40(1-2):119-28.
citation: Teasdale JD, Segal ZV, Williams JM, Ridgeway VA, Soulsby JM, Lau MA. Prevention of relapse/recurrence in major depression by mindfulness-based cognitive therapy. J Consult Clin Psychol. 2000 Aug;68(4):615-23. doi: 10.1037//0022-006x.68.4.615.
citation: Tugade MM, Fredrickson BL. Resilient individuals use positive emotions to bounce back from negative emotional experiences. J Pers Soc Psychol. 2004 Feb;86(2):320-33. doi: 10.1037/0022-3514.86.2.320.
citation: Uttl B. North American Adult Reading Test: age norms, reliability, and validity. J Clin Exp Neuropsychol. 2002 Dec;24(8):1123-37. doi: 10.1076/jcen.24.8.1123.8375.
citation: Watson D, Clark LA, Tellegen A. Development and validation of brief measures of positive and negative affect: the PANAS scales. J Pers Soc Psychol. 1988 Jun;54(6):1063-70. doi: 10.1037//0022-3514.54.6.1063.
citation: Watts BV, Schnurr PP, Mayo L, Young-Xu Y, Weeks WB, Friedman MJ. Meta-analysis of the efficacy of treatments for posttraumatic stress disorder. J Clin Psychiatry. 2013 Jun;74(6):e541-50. doi: 10.4088/JCP.12r08225.
citation: Westbrook C, Creswell JD, Tabibnia G, Julson E, Kober H, Tindle HA. Mindful attention reduces neural and self-reported cue-induced craving in smokers. Soc Cogn Affect Neurosci. 2013 Jan;8(1):73-84. doi: 10.1093/scan/nsr076. Epub 2011 Nov 22.
citation: Azam MA, Katz J, Mohabir V, Ritvo P. Individuals with tension and migraine headaches exhibit increased heart rate variability during post-stress mindfulness meditation practice but a decrease during a post-stress control condition - A randomized, controlled experiment. Int J Psychophysiol. 2016 Dec;110:66-74. doi: 10.1016/j.ijpsycho.2016.10.011. Epub 2016 Oct 18.