Multi-center, randomized controlled efficacy and comparative-effectiveness study evaluating ketamine, stellate ganglion blocks, combination treatment, and sham treatments for posttraumatic stress disorder and traumatic brain injury-associated headache: a study protocol.

Abstract

Posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI) are conditions that share common mechanisms and are highly co-prevalent with each other and chronic pain. This pragmatic study will compare ketamine infusions to stellate ganglion blocks (SGB), their combination, and a placebo-sham-controlled arm. A double-blind study conducted at 3 U.S. and Ukrainian sites will be performed. Two hundred ten patients with PTSD and/or TBI-associated headache will be allocated in a 2:2:2:1 ratio to receive SGB/placebo ketamine, ketamine/sham SGB, ketamine/SGB, and placebo/sham. The bivariate co-primary outcome will evaluate change in Headache Impact Test and PTSD Checklist depending on diagnosis, at 4 weeks. Participants who experience a positive binary outcome will remain in the study through 6 months or until their outcome becomes negative. Because PTSD and TBI have no discrete pathophysiological mechanisms and are co-prevalent with pain and psychopathology, they are associated with poor outcomes, polypharmacy, and high non-adherence rates, indicating a need for minimally invasive treatments that obviate these barriers. Whereas both therapies have evidence underpinning efficacy, results in clinical trials are conflicting. This study will provide real-world evidence in generalizable populations on the efficacy and comparative-effectiveness of ketamine and SGB, alone and in combination, with the possibility of changing clinical guidelines. www.clinicaltrials.gov identifier is NCT06608277. This protocol paper, whose source of funding from the U.S. Department of Defense stemmed from Congressional requests outlined in all National Defense Authorization Acts this decade, describes a multi-center study being conducted at civilian and military treatment facilities in the U.S. and Ukraine comparing stellate ganglion blocks to ketamine, alone and in combination, for posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI). One in 7 people will receive placebo ketamine (saline) and a sham stellate ganglion block and 2 in 7 will receive both treatments. The main outcome measures are PTSD symptoms and TBI-related headache measured 4 weeks after treatment, with individuals who experience benefit continuing in the study for up to 6 months. Additional studies will seek to determine whether testing pain responses to stimuli and certain markers in the blood can help identify who is likely to respond to treatment.