Efficacy and Safety of Stellate Ganglion Block for Post-traumatic Stress Disorder in Veterans

Veterans Health Administration, Decatur PA

Investigators

Abstract

Project Summary / Abstract (40 lines) Stellate Ganglion Block (SGB) is a rapid-acting intervention that may directly target PTSD biology. Positive case-studies and preliminary results from our team suggest clinically robust and significant benefits for up to 6- months. Two randomized controlled trials, however, yielded conflicting results and had methodological limitations, making interpretation of results inconclusive. Neither trial evaluated durability beyond 8-weeks, safety, or biological mechanisms along with clinical outcomes. Veteran demand for SGB for PTSD is high, creating time-sensitive urgency for a more definitive study in VA. We propose a 4-year, multi-site, two-phase, three-arm, (SGB-experimental condition, Sham-placebo control, Wait-List Control (WLC)-for time, expectancy and safety) parallel-group, triple-blind, prospective randomized controlled trial (RCT) of SGB for PTSD. The sample will include 360 treatment-seeking Veterans with chronic PTSD randomized 1:1:1 to the three treatment arms using an adaptive randomization procedure. Phase I is a 12-week RCT with the primary aims of evaluating: a) within and between group differences in the change in PTSD symptom severity from pre- to 8- weeks post-intervention, b) durability of symptom reduction after SGB over 12 weeks, and c) safety (i.e., SGB will be as safe as Sham and WLC). Phase II is a 12-week open-label extension period where subjects in all groups are offered active SGB if eligible (PTSD scores > inclusion criteria scores at the primary Phase I endpoint of 8-weeks). Phase II is important because it allows evaluation of “enhanced dosing” (second SGB for those in the SGB arm), it allows all subjects to receive active intervention if they want, which also provides a larger sample of SGBs for exploratory pooled analyses, and it allows for analyses of durability over a longer time period for those in remission after Phase I. Another secondary aim is to test the hypothesis that SGB will be more biologically active than Sham or WLC by showing greater pre- to post-intervention reduction in highly PTSD-relevant fear-potentiated startle. We will also explore clinical and biological predictors of an SGB response (i.e., significant reduction in CAPS-5 scores). This superiority study is designed to expect and detect statistically and clinically important 30% PTSD symptom reduction from baseline to 8-week endpoint for SGB,15% reduction for Sham and 5% reduction for WLC in a sample with moderately severe PTSD (baseline score of 65+18). With these assumptions we require a sample size of 262 subjects to test the primary hypothesis of clinical efficacy. We will sample 360 subjects to account for 15% attrition, missing data, a 5% failed-block rate and site variability. It is critical to ensure adequate power for this time-sensitive study. Multivariate analysis of variance (MANOVA) will be used to test the null hypothesis of no differences in baseline PTSD symptoms and subsequent retest of PTSD symptoms while simultaneously adjusting for any significant covariates. Analyses will be performed on missing data due to loss-to-follow-up in order to determine if any potential bias exists once missing data are withdrawn. Additional analyses will be conducted to determine interactions and moderating/mediating effects while simultaneously adjusting for other covariates in the model. Details for analyses of our three primary aims are in the data analysis section of the Research Plan. Our leadership team has extensive clinical and research experience with clinical trials, the use and adaptation of SGB for PTSD, and a national initiative to provide SGB to PTSD patients on a compassionate care basis. The proposed definitive study will guide rational use of SGB for PTSD in VA, will stimulate further research about dose, timing, biological mechanisms and clinical predictors of outcome, and will have established VA sites poised for further SGB research and clinical practice.