Clinical trial NCT05169190: Stellate Ganglion Block for PTSD
Official title: Efficacy and Safety of Stellate Ganglion Block for Post-traumatic Stress Disorder in Veterans
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Post-traumatic Stress Disorder
Keywords: Veterans
Trauma Disorders
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
Collaborators: name: Analydata, Inc.
First posted: 2021-12-23
Enrollment: 360
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a two-phase, three-arm (SGB vs Sham vs Wait List Control (WLC)), parallel-group (n=120 in each), triple-blind, prospective randomized controlled clinical trial (RCT). Phase I is 12-weeks and is the primary three-group RCT. Phase II is a 12-week open-label extension period where subjects in all groups are offered active SGB if eligible, defined as having PTSD scores \> study inclusion criteria scores at the Phase I endpoints.
Primary purpose: TREATMENT

Brief summary: Posttraumatic Stress Disorder (PTSD) is a debilitating condition that affects about 15% of Veterans. Current treatments for Veterans with PTSD include medications and psychological therapies that help to process and desensitize to traumatic events. While effective for many, these treatments do not work for all patients, and many may refuse them. Stellate Ganglion Block (SGB), established to treat pain and other conditions, has shown promise for PTSD: early small studies show it may work fast and greatly reduce symptoms. However, data from larger studies are not clear about SGBs effects. A definitive trial is needed, especially for the Veteran population. This large, well-powered, randomized, sham-controlled trial of SGB for PTSD will assess the short-term efficacy of this intervention, the durability of the effects and the safety of the treatment. Additionally, this study will provide critically important information about biological effects of SGB and potential mechanisms of action. This timely study is critical to help VA clinicians better decide about the merits of SGB for PTSD.

Detailed description: Stellate Ganglion Block (SGB) is a rapid-acting intervention that may directly target PTSD biology. Positive case-studies and preliminary results from the investigators' 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. The investigators 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 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 both primary Phase I endpoint of 8-weeks and durability endpoint of 12-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. The investigators will also explore clinical and biological phenotypic 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 the investigators require a sample size of 262 subjects to test the primary hypothesis of clinical efficacy. The investigators will sample 360 subjects to account for 10% attrition, 5% missing data, a 5% failed-block rate and will oversample due to site variability. It is critical to ensure adequate power for this time-sensitive study. General linear mixed models (repeated multivariate analysis of variance (MANOVA)) will be used to evaluate the primary clinical hypothesized effects of intervention (SGB) on the clinical outcome of PTSD symptom severity (CAPS-5) over time (pre- to post-treatment to follow-up), controlling for baseline severity of symptoms and demographic characteristics (e.g., age, gender) in comparison with placebo control group (Sham) and WLC group with assumption of intent to treat while simultaneously adjusting for any significant covariates. Cohen's d within and between subjects will be calculated. 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. Details for analyses of the three primary aims are in the data analysis section of the Research Plan. The 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.

Eligibility criteria: Inclusion Criteria:

* Veterans of any military branch
* DSM-5 criteria for chronic PTSD on the Clinician Administered PTSD Scale (CAPS-5)
* at least moderate PTSD with a total CAPS-5 score of \> 26
* having had at least one trial of an evidence-based treatment (EBT) for PTSD

Verification of an EBT trial will be by:

* subject report of engaging in the EBT (whether it be psycho- or pharmaco-therapy)
* CPRS or other medical record system (if outside VA) verification to determine that the dose and time (applies to both meds and therapy) was an adequate trial OR that they clearly did not finish the EBT due to clear aversion

  * They will be eligible if they did not finish the EBT due to aversion, but they must have had a trial and be fully informed during informed consent for this study of the available clinical treatment options
  * Eligible persons may have other symptoms that are commonly comorbid with PTSD (e.g., anxiety, moderate depression)
  * Severe primary depression will be an exclusion (see "Exclusion criteria" below)
  * This strategy will provide a feasible and generalizable sample
  * Women and minorities will be recruited

Exclusion Criteria:

* clear current and past six-months psychosis clearly not related to PSTD hypervigilance,
* substance dependence (clear evidence of tolerance and/or withdrawal) within the past 6 months
* thyroid disease and other contraindications to SGB (anatomic abnormalities of the anterior cervical spine; cardiac/pulmonary compromise; acute illness/infection; coagulopathy/bleeding disorder; allergic reactions/contraindications to local anesthetic or contrast dye, prior anterior neck surgery, anterior neck skin abnormalities (rash or eruptions))
* decisional incapacity (e.g., dementia, clear evidence of testing that signifies incapacity to consent), OR Montreal Cognitive Assessment score \<18
* centrally acting medications that have a potential effect on biological expression
* pain levels requiring opiate medications
* known exposure to chemicals or physical trauma that cause permanent neuropsychiatric sequelae
* severe depression (Quick Inventory of Depression-SR16 (QIDS-SR16 score \>18) that is deemed more clinically significant than PTSD (i.e., depression, cluster D PTSD, and minimal symptoms from cluster B, C, and E)
* high risk of acute suicidality
* a diagnosed and untreated moderate or severe sleep breathing disorder (SBD), OR a high risk of a SBD as indicated by snoring \>50% of nights plus one of

  * any witnessed apnea
  * feeling non-refreshed in the morning \>50% of mornings
  * daytime sleepiness indicated by falling asleep with routine tasks such as watching TV or reading
* clear treatment non-adherence indicated by stopping treatment or \>3 missed appointments in the course of at least three PTSD EBTs
* past clear and chronic PTSD prior to military service
* current active psychotherapy for PTSD (they may suspend therapy if chosen by subject and therapist)
* pregnancy
* having had any prior SGB
* unstable dose(s) of medication for depression, anxiety, PTSD, or for sleep, or any other psychoactive medication for 8-weeks prior to intervention
* unwillingness to continue active medications at the same doses for the duration of the trial

  * a person who is on a stable medication dose for \> 8 weeks who meets inclusion criteria and will continue these medications for the trial duration will not be excluded

Primary outcomes:
measure: Clinician Administered PTSD Scale-5
timeFrame: 8 weeks after SGB, Sham, or WLC enrollment
measure: Safety - Adverse Events and Side Effects from Treatment
timeFrame: 8 weeks after SGB, Sham, or WLC enrollment
Secondary outcomes:
measure: Peripheral Psychophysiology Startle Response
timeFrame: 8 weeks after SGB, Sham, or WLC enrollment
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: VA Long Beach Healthcare System, Long Beach, CA
state: California
city: Tampa
country: United States
facility: James A. Haley Veterans' Hospital, Tampa, FL
state: Florida
city: Minneapolis
country: United States
facility: Minneapolis VA Health Care System, Minneapolis, MN
state: Minnesota
city: Salt Lake City
country: United States
facility: VA Salt Lake City Health Care System, Salt Lake City, UT
state: Utah
city: White River Junction
country: United States
facility: White River Junction VA Medical Center, White River Junction, VT
state: Vermont
city: Madison
country: United States
facility: William S. Middleton Memorial Veterans Hospital, Madison, WI
state: Wisconsin
Study officials:
affiliation: VA Long Beach Healthcare System, Long Beach, CA
name: Michael Hollifield, MD
role: PRINCIPAL_INVESTIGATOR
References: