Treatment of Fibromyalgia and PTSD With Live and Inactive Vagus Nerve Stimulation With PEPC

The investigators' goal is to test whether providing simultaneous non-drug treatments for both FM and PTSD improves symptom impact on both conditions. tAN, a non-invasive neuromodulatory technique applied to the auricular branch of the vagus and trigeminal nerves, has preliminary efficacy in reducing chronic pain and reducing PTSD severity in Veterans with PTSD and in an opioid withdrawal population. PE-PC is a form of Prolonged Exposure, a gold standard treatment for PTSD, that is designed for integrated care and effectively reduces PTSD severity. In addition, tAN applied with the proposed device significantly reduced PCL-5 scores by 35% from baseline to Day 5 in adults withdrawing from opioid. Within this high-risk comorbid population, adding a non-opioid pain intervention provided within the context of effective PTSD treatment promises to increase impact on both pain and PTSD. The combination requires minimal additional 'in clinic' time, may be provided in-home or via telehealth, and each is available in VA standard care. Study results can inform implementation for this combined intervention and speed its use in clinics. Thus, more Veterans will have access to effective care for FM and PTSD, supporting a priority of POU-AMP and the VA National Strategy for Preventing Suicide (2018). In summary, the investigators will examine whether pain is reduced with PTSD treatment in FM, and whether addition of tAN can augment this effect compared to sham.

Design: The investigators will randomize 180 Veterans with co-morbid FM and PTSD from across AVAHCS to receive: 1) tAN for pain + PE-PC or 2) sham tAN + PE-PC. tAN administered daily for 2 hours for 4 weeks. PE-PC is provided in six 30-minute sessions up to 3 times per week. Assessments will be collected at Intake, Baseline/Post Run-In, Week 2, Week 4, and \[4 month follow-up\]. Primary outcome will be posttreatment (week 4) Pain, Enjoyment and General Activity Scale (PEG). Secondary outcomes include Fibromyalgia Impact Questionnaire Revised (FIQR), Polysymptomatic Distress Scale (PSD), PTSD (PCL-5 weekly version). Biomarker analysis will examine the association of HRV \[(baseline \& trauma cued).

Aim (1): Examine additive efficacy of 1) tAN+PE-PC and 2) sham tAN+PE-PC on FM-related pain interference and intensity in the context of PE-PC for PTSD \[Primary Outcome: PEG scale and PTSD symptom severity \[Secondary Outcome: PCL5, weekly\].

Hypothesis 1a: tAN+PE-PC will result in larger reductions in pain interference and intensity than sham tAN+PE-PC (\[Baseline\] to Week 4). Differences will be maintained at \[4-month follow-up\].

Hypothesis 1b: tAN+PE-PC will result in larger reductions in PTSD severity than sham tAN+PE-PC (\[Baseline\] to Week 4). Differences will be maintained at \[4-month follow-up\].

Exploratory Aim: Evaluate changes in HRV (baseline \& trauma cued) as a biomarker of response associated with FM-related pain and PTSD severity improvement in tAN+PE-PC and sham tAN+PE-PC.

Exploratory Hypothesis: tAN+PE-PC will result in greater change in HRV compared to sham+PE-PC. This proposal targets the Pain and Opioid Use Actively Managed Portfolio (POU-AMP) research priority of pragmatic clinical trials for treatment of painful conditions using non-pharmacological approaches. The long-term objective is improving Veteran health through focused combined intervention for FM and PTSD.

• tAN plus PEPC (Device), also known as Sparrow Link: The research version of Spark's Sparrow Ascent for vagus and trigeminal nerve stimulation provided through a sticker that attaches to the ear. This device allows the patient to self apply the device in a home setting. It is FDA cleared and available in VA. Stimulation is combined with 6, 30 minute sessions on Processing Emotions in Primary Care (PEP) brief PTSD psychotherapy provided over 4 weeks.
• sham plus PEPC (Device), also known as Sparrow Link: Same device as active condition but programmed with sham parameters including suprasensory stimulation followed by ramp down. Sham is combined with 6, 30 minute sessions on Processing Emotions in Primary Care (PEP) brief PTSD psychotherapy provided over 4 weeks.

Primary outcomes

• Pain Intensity [Pain, Enjoyment, and General Activity Scale (PEG)] [Intake, Baseline, Week 2, Week 4, Week 8, 4 month followup]: Single item rating past week average intensity of pain on a scale from 0 (none) to 10 (As bad as I can imagine)
• Pain Interference with Enjoyment [Pain, Enjoyment, and General Activity Scale (PEG)] [Intake, Baseline, Week 2, Week 4, Week 8, 4 month followup]: Single item rating of average pain interference with enjoyment of life over the past week on a 0 (no interference) to 10 (completely interfered).
• Pain Interference with Activity [Pain, Enjoyment, and General Activity Scale (PEG)] [Intake, Baseline, Week 2, Week 4, Week 8, 4 month followup]: Single item rating of average pain interference in general activity over the past week on a 0 (no interference) to 10 (completely interfered).

Secondary outcomes

• Post-traumatic stress disorder (PTSD) Checklist for DSM 5 (PCL-5) [Intake, Baseline, Week 2, Week 4, Week 8, 4 month followup]: Total sum of each of 20 items covering PTSD symptom ratings for the past week each scored on a 0 (not al all) to 4 (extremely) scale. Total score ranges from 0 to 80.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

1. Subjects must be any era Veterans reporting fibromyalgia (FM) and post-traumatic stress disorder (PTSD) symptoms (PTSD Checklist for DSM-5 (PCL-5) ≥ 28; FM confirmed with ACR Diagnostic Criteria and pain score at least 4/10 for 3 months
2. Subjects must speak English
3. If subjects are taking psychotropic medication, 2-weeks on stable dose prior to enrollment and agreement to maintain current medications until after the 4-month follow-up visit

Exclusion Criteria:

1. Subjects must not have other primary clinical issues that would interfere with fibromyalgia (FM) or post-traumatic stress disorder (PTSD) treatment such as recent stroke or severe heart disease
2. Subjects must not have a level of suicide risk that requires intervention as determined by item 9 on PHQ-9 with follow-up risk assessment by study staff
3. Subjects must not have severe cognitive impairment that interferes with PE-PC (unable to retain information in acute interaction)
4. Subjects must not have unmanaged psychosis or bipolar disorder
5. Subjects must not have moderate to severe substance use disorder in the past 8 weeks
6. Subjects must not be currently receiving talk therapy for trauma-related symptoms or fibromyalgia (FM)
7. Subjects must not be currently pregnant or lactating given risk of pre-term labor and interference of oxytocin with vagus nerve stimulation (VNS) effects

• Sheila A.M. Rauch, PhD, Principal investigator, Atlanta VA Medical and Rehab Center, Decatur, GA
• Anna Woodbury, MD, Principal investigator, Atlanta VA Medical and Rehab Center, Decatur, GA