Ketamine, SGB and Combination Treatment for TBI
- Conditions
- Posttraumatic HeadachePosttraumatic Stress Disorder
- Interventions
- Procedure: Group A active comparatorDrug: Group B active comparatorCombination Product: Group C ExperimentalOther: Group D Placebo Comparator
- Registration Number
- NCT06608277
- Lead Sponsor
- Northwestern University
- Brief Summary
Post-Traumatic Stress Disorder (PTSD) and traumatic brain injury (TBI) with associated headache are amongst the most common injuries sustained by our deployed forces in Iraq and Afghanistan, as well as in more recent conflicts in Eastern Europe and the Middle East. This study aims to determine whether a procedural intervention (stellate ganglion block (SGB)) or medication (ketamine), alone or in combination, can alleviate PTSD and TBI-associated headache. Determining efficacious treatments in a randomized, double-blind, placebo-controlled, multicenter study trial may improve quality of life in those with TBI and PTSD, and identifying factors associated with treatment outcome (personalized medicine) may enhance selection, thereby improving the risk: benefit and cost-effectiveness ratios.
Primary Objectives:
1. To determine the efficacy of SGB and ketamine infusion as stand-alone treatments for TBI-related headache;
2. To determine the efficacy of SGB and ketamine infusion as stand-alone treatments for PTSD;
3. To determine the comparative effectiveness of SGB and ketamine infusion, and the effect of combination treatment on TBI-related headache and PTSD;
4. Exploratory Aim 1: To determine the effects of SGB, ketamine infusion, and the combination on structural and functional MRI, biomarker levels and pain thresholds and tolerance;
5. Exploratory Aim 2: To identify factors associated with treatment responders overall and for individual treatment groups.
Secondary Objectives:
1. Exploratory Aim 1: To determine the effects of SGB, ketamine infusion, and the combination on structural and functional MRI, biomarker levels and pain thresholds and tolerance (Biomedical levels and MRI not included at Northwestern University Site).
2. Exploratory Aim 2: To identify factors associated with treatment responders overall and for individual treatment groups.
- Detailed Description
This is a multicenter randomized, double-blind (subject, evaluator) placebo-controlled parallel-group clinical trial where 175 eligible subjects will be randomized into 1 of 4 groups (described below) using a 2:2:2:1 ratio. The purpose of the trial is to test the efficacy and comparative effectiveness of SGB and ketamine infusion on PTSD and post-traumatic headache. There are no reliably effective treatments for either PTSD or TBI-associated headaches, with preliminary and/or conflicting results suggesting efficacy for both SGB and ketamine for both conditions.
The first three groups will receive at least one intervention, with a smaller number receiving sham SGB/ placebo ketamine, which is necessary to determine efficacy and serve as a comparator. Several patient-reported outcomes, including quality of life measures, will be collected at baseline and the primary endpoint at 4 weeks. Those with a positive categorical response (described under data collection) will be followed further at 8 and 12 weeks. Those with negative outcomes will exit the study and be followed as an observational cohort where they will be eligible for non-study measures as determined by the treating providers. This may include other novel treatments such as using higher doses of ketamine, sympathetic blocks with botulinum toxin and liposomal bupivacaine, and the use of neuromodulation.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 175
- Adults 18 years or older
- Stable doses of medications for > 2 weeks for TBI and/or PTSD
- For TBI-associated headache with or without PTSD: HIT-6 score of >/=53. For PTSD with or without TBI-associated headache: PCL-5 score >/=33 OR. For those with TBI and PTSD, and a HIT-6 score < 53 and PCL-5 score of <33, individuals with a HIT-6 score of 50-52 and a PCL-5 score of 31 or 32 will be included.
- Duration of chronic TBI or PTSD > 3 months
- Ketamine infusion or SGB within the past 6 months
- Serious medical or psychiatric conditions other than TBI or PTSD that could affect cognition (e.g., dementia, Parkinson's Disease)
- Elevated intracranial pressure
- For TBI, prior history of headache that can explain the headache intensity (i.e., headache not attributable to TBI)
- Active psychosis or poorly controlled non-injury or PTSD-related psychiatric condition (e.g., bipolar disorder)
- Poorly controlled medical conditions that could be exacerbated by treatment (e.g., unstable angina)
- Pregnancy (women of childbearing age who can become pregnant will have to take a pregnancy test)
- Non-fluency in English (poor generalizability to military and veteran populations, instruments not validated for use or translated in many languages)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group A =Stellate ganglion block (SGB) with bupivacaine (LA) plus placebo ketamine (midazolam) Group A active comparator Stellate ganglion block with the local anesthetic (LA) bupivacaine and placebo (1-7 mg midazolam + normal saline) ketamine. The stellate ganglion block will be performed with approximately 8 mL bupivacaine using ultrasound or fluoroscopic guidance. The placebo ketamine will consist of an initial 1-4 mg bolus of midazolam followed by boluses or an infusion (in normal saline) of midazolam up to 7 mg, over 30-60 minutes. Group B = Sham SGB plus ketamine infusion Group B active comparator Sham SGB will be 1-2 mL of saline given subcutaneously using ultrasound or fluoroscopic guidance. The ketamine will consist of Prior to the sham Stellate Ganglion Block procedure, the study drug ketamine or normal saline will be administered by one of the study team physicians. 100 ml bag will be administered by bolus/infusion or intermittent boluses up to 0.3 mg/kg). The ketamine infusion will start before the sham block where patients will be given 1-4 mg of midazolam + up to 0.3 mg/kg of ketamine, as bolus doses. Over the next 30-60 minutes patients will receive between 0.5-1 mg/kg total dose of ketamine, + additional midazolam as needed. Group C = Stellate ganglion block (SGB) with bupivacaine LA plus ketamine infusion Group C Experimental These patients will receive both SGB with bupivacaine + ketamine as described above. Group D = Sham SGB plus placebo ketamine (midazolam) Group D Placebo Comparator These patients will receive the sham SGB + placebo ketamine as described above.
- Primary Outcome Measures
Name Time Method Headache Impact Test (HIT-6) 4 weeks Headache Impact Test (HIT-6) is a 6-item instrument that measures the impact of headaches, scored from 36-78 with higher scores indicating greater disability impact of headaches in a 1-month period that has been validated for a variety of headache conditions, including tension-type headache and migraine.
PTSD Checklist (PCL-5) 4 weeks PTSD Checklist (PCL-5) is a psychometrically-validated 20-item instrument that measures the quality of life in people with posttraumatic stress disorder (PTSD_, scored from 0-80 with higher scores indicating greater disability assesses 20 DSM-5 symptoms of posttraumatic stress disorder.
- Secondary Outcome Measures
Name Time Method Central Sensitization Inventory (CSI) 8 weeks after procedure A 25-item survey which measures central sensitization (amplified nervous system response to sensory stimuli), scored from 0-100 with higher scores indicating greater sensitization sensitization. It is a self-reported tool that consists of statements related to current health symptoms rated on a 5-point Likert scale, with a score of 40 being the cut off value for central sensitization
Headache intensity 12 weeks after procedure Average and worst headache scores (0-10 numerical rating scale (NRS), overall pain (0=no pain, 10=worst pain imaginable).
NRS scale)Headache frequency 8 weeks after procedure Days per week with scores greater or equal to 2, and 7/10 (2= mild headache, 7=severe headache)
Hospital Anxiety and Depression Scale (HADS) 12 weeks 14-item instrument with questions assessing anxiety and depression (7 each) scored from 0-3. For each subscale (anxiety and depression), scores range from 0-21, with higher scores indicating greater pathology.
Analgesic or psychotropic medication reduction 12 weeks after procedure An analgesic or psychotropic medication reduction identified as a \> 20% reduction in opioid, barbiturate or benzodiazepine, or cessation of nonopioid analgesic, or \> 50% reduction in non-benzodiazepine sedation or psychotropic medication (e.g., antidepressant or antipsychotic).
Headache Impact Test (HIT-6) 12 weeks Headache Impact Test (HIT-6) is a 6-item instrument that measures the impact of headaches, scored from 36-78 with higher scores indicating greater disability impact of headaches in a 1-month period that has been validated for a variety of headache conditions, including tension-type headache and migraine.
Quality of Life after Brain Injury scale (QoLIBRI) 12 weeks 37-item scale with questions ranging from 1 (not at all) to 5 (very true), with a score ranging from 0-100 (higher numbers indicate better quality of life) calculated from the mean score minus 1, multiplied by 4.
Patient Global Impression of Change Scale 12 weeks 7-item Likert scale with scores ranging from 0 (worse or no change) to 7 (a great deal better)
Positive categorical outcome 12 weeks Positive is \>/= 4 on the PGIC scale and \>/= 6-point reduction in HIT-6 and/or a \>/= 10-point reduction in PCL-5.
Sheehan Suicidality Tracking Scale (S-STS) 12 weeks after procedure The S-STS is a short scale designed to assess and monitor suicidality over time and is very sensitive to changes in treatment. The survey has 8 questions with each scored from none (0) to extremely (4).
outcomes.International Trauma Questionnaire 12 weeks 18-question survey that measures the impact PTSD has on an individual, and helps phenotype PTSD (i.e., into complex PTSD or non-complex). Each question is scored from 0-4 (range 0-72), with higher scores indicating greater disease burden.
Trial Locations
- Locations (3)
Anesthesiology Pain Medicine Center
🇺🇸Chicago, Illinois, United States
Walter Reed National Military Medical Center
🇺🇸Bethesda, Maryland, United States
First Medical Union
🇺🇦Lviv, Lviv Oblast, Ukraine