Efficacy of Cervical Sympathetic Blocks for PTSD

Official title

Efficacy of Cervical Sympathetic Blocks for Post-traumatic Stress Disorder: a Randomized Control Trial

Overview

Millions of people suffer from anxiety disorders, including posttraumatic stress disorder (PTSD)-a condition that can profoundly disrupt daily life. Although treatments like therapy and medication help many, there is still a major need for more effective and faster-acting options. In recent studies, a procedure called cervical sympathetic block (CSB)-an injection near a nerve cluster in the neck-has shown promise in reducing PTSD symptoms, as measured by standardized tools like the CAPS (Clinician-Administered PTSD Scale). In this study, the investigators will conduct a double-blind, randomized controlled trial comparing CSB to a sham (placebo) injection in patients with PTSD. The investigators will assess changes in PTSD symptoms and also monitor physiological markers (like pupil response, temperature, and heart rate variability) to better understand how the treatment works and to improve the precision of future therapies.

Detailed description

The investigators aim to determine whether cervical sympathetic blocks (CSBs) can reduce symptoms of posttraumatic stress disorder (PTSD). If effective, this approach could offer a rapid, legal, and scalable intervention for mental health conditions, in contrast with emerging psychedelic therapies. This research has the potential to transform treatment practices for PTSD and related disorders by providing a controlled, procedure-based option that modulates the autonomic nervous system. In addition to assessing symptom relief, the study will explore physiologic markers of sympathetic modulation, which may help identify objective indicators of treatment success. This could deepen our understanding of the neural mechanisms underlying PTSD and mental health more broadly, with implications for neuroscience, psychology, and clinical care.

Interventions

• Procedure Cervical sympathetic nerve block
  Patients will receive a CSB.
• Procedure Subcutaneous sham injection
  Patients will receive a subcutaneous sham injection of saline.
• Drug Ropivacaine
  The CSB group will receive ropivacaine 0.5% 10ml.
• Drug Normal Saline
  The control group will receive 3 ml of normal saline in the sham injection.

Primary outcome measures

• Clinician-Administered PTSD Scale (CAPS-5) scores [Time frame: Baseline (1 month before the block), 30 and 90 days post-block.]

Secondary outcome measures (12)

• Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5) scores [Time frame: Baseline (1 month before the block), then 7, 14, 30 and 90 days post-block]
• Patient Health Questionnaire-9 (PHQ-9) [Time frame: 2 weeks before the block and 2 weeks post-block]
• State and Trait Anxiety Scale (STAI) [Time frame: 2 weeks before the block and 2 weeks post-block]
• Generalized Anxiety Disorder scale (GAD-7) [Time frame: 2 weeks before the block and 2 weeks post-block]
• Positive and Negative Affect Schedule (PANAS) [Time frame: 2 weeks before the block and 2 weeks post-block]
• Pittsburgh Sleep Quality Index (PSQI) [Time frame: 2 weeks before the block and 2 weeks post-block]
• The Satisfaction With Life Scale [Time frame: 2 weeks before the block and 2 weeks post-block]
• Scales of Psychological Well-Being [Time frame: 2 weeks before the block and 2 weeks post-block]
• Peace of Mind Scale [Time frame: 2 weeks before the block and 2 weeks post-block]
• The Emotion Regulation Questionnaire Short Form [Time frame: 2 weeks before the block and 2 weeks post-block]
• Harmony in Life Scale [Time frame: 2 weeks before the block and 2 weeks post-block]
• The Perth Alexithymia Questionnaire Short Form [Time frame: 2 weeks before the block and 2 weeks post-block]

Eligibility criteria

Inclusion criteria

• Male or female, 18 to 70 years of age, inclusive, at screen.
• Able to read, understand, and provide written informed consent in English prior to screening, and likely to comply with study procedures and communicate effectively with study personnel regarding adverse events or other clinically important information.
• Diagnosed with PTSD prior to screening, according to the criteria defined in the Diagnosis and Statistical Manual of Mental Disorders, Fifth Edition. The diagnosis of PTSD will be made by a trained study staff member and supported by the Structured Clinical Interview for DSM Disorders (SCID).
• Meet the threshold of CAPS-5 score of >20 during screening.
• Concurrent psychotherapy will be allowed if the type (e.g., supportive, cognitive behavioral, insight-oriented, et al) and frequency (e.g., weekly or monthly) of the therapy has been stable for at least 4 weeks prior to screening and if the type and frequency of the therapy is expected to remain stable during the course of the subject's participation in the study.
• Concurrent antidepressant therapy (e.g. SSRI or SNRI) will be allowed if the therapy has been stable for at least 4 weeks prior to screening and if it is expected to remain stable during the course of the subject's participation in the study.
• In sufficiently good health to proceed with a low-risk elective procedure, characterized using the American Society of Anesthesiologists (ASA) physical status classification system as Class I, II, or III.

ASA Class III participants whose functional impairment is directly related to a psychiatric diagnosis (depression, anxiety or PTSD) will be included.

Exclusion criteria

• Allergy to local anesthetics
• Severe coagulopathy
• Female that is pregnant or breastfeeding.
• Female with a positive pregnancy test at screening or baseline.
• Total CAPS-5 score £20 at screening.
• Current diagnosis of a Substance Use Disorder (SUD; Abuse or Dependence, as defined by DSM-V) rated "moderate" or "severe" per criteria of the SCID, or Alcohol Use Disorder rated "moderate" or "severe" per SCID criteria. The following categories of SUD will NOT be excluded: nicotine dependence; alcohol or substance use disorder rated "mild"; alcohol or substance use disorder of any severity in remission, either early (3-12 months) or sustained (>12 months) time frames.
• Current diagnosis of Axis I disorders other than Dysthymic Disorder, Generalized Anxiety Disorder, Social Anxiety Disorder, Panic Disorder, Agoraphobia, Specific Phobia, or Bipolar II Disorder (unless one of these is comorbid and clinically unstable, and/or the focus of the participant's treatment for the past six months or more)
• History of schizophrenia or schizoaffective disorders, or a psychotic disorder as defined by SCID interview.
• Any Axis I or Axis II Disorder, which at screening is clinically predominant to their PTSD or has been predominant to their PTSD at any time within six months prior to screening.
• In the judgment of the investigator, the subject is at significant risk for suicidal behavior during the course of his/her participation in the study.
• A neurological disorder including:

• Has dementia, delirium, amnestic, or any other cognitive disorder
• Encephalitis, meningitis, degenerative central nervous system disorder (e.g., Alzheimer's or Parkinson's Disease), epilepsy, mental retardation
• Any other disease/accident/intervention associated with significant injury to or malfunction of the central nervous system with ongoing clinically significant sequelae, or in the view of the investigator poses a risk for participation in this study.
• A cardiovascular disorder including:

• Uncontrolled hypertension
• Congestive heart failure NYHA Criteria >Stage 2
• Atrial fibrillation or resting heart rate <50 or >105 beats per minute at screening or randomization
• Any clinically significant conduction abnormalities (eg 2nd degree AV nodal block or left bundle branch block)
• QTcF (Fridericia-corrected) >= 450 msec at screening or randomization
• Any cardiovascular disorder that would merit categorization of patient as ASA Class III or higher
• A pulmonary/respiratory disorder including:

• Diagnosed Obstructive Sleep Apnea or STOPBANG score of 5 or higher
• History of difficult airway in surgical setting
• Any pulmonary / respiratory disorder that would merit categorization of patient as ASA Class III or higher
• Clinically significant liver disease, determined by LFTs within the past 6 months.
• Clinically significant kidney disease determined by GFR (<40 mL/min, Cockcroft-Gault Equation)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Zhang J, Liu Y, Li H, Hu Y, Yu S, Liu Q, Chen Y. Stellate Ganglion Block Improves Postoperative Cognitive Dysfunction in aged rats by SIRT1-mediated White Matter Lesion Repair. Neurochem Res. 2022 Dec;47(12):3838-3853. doi: 10.1007/s11064-022-03800-z. Epub 2022 Oct 31. PMID 36315371
• Yu K, Zhang XK, Xiong HC, Liang SS, Lu ZY, Wu YQ, Chen Y, Xiao SJ. Stellate ganglion block alleviates postoperative cognitive dysfunction via inhibiting TLR4/NF-kappaB signaling pathway. Neurosci Lett. 2023 Jun 11;807:137259. doi: 10.1016/j.neulet.2023.137259. Epub 2023 Apr 17. PMID 37075883

Identifiers

NCT: NCT07087015 · 81697

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗