A Phase 2 interventional study of Group A active comparator and Group B active comparator in Posttraumatic Headache and Posttraumatic Stress Disorder, sponsored by Northwestern University. Recruiting at 3 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-05-01.
Sponsored by Northwestern University · Phase 2, Interventional, and Treatment
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:
Secondary Objectives:
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. There will also be patient-reported outcome measures recorded at 1 and 2 weeks. Those with a positive categorical response (described under data collection) at 4 weeks 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, left-sided sympathetic blocks, sympathetic blocks with botulinum toxin and liposomal bupivacaine, and the use of neuromodulation.
For all patients who continue to experience a positive categorical outcome, unblinding will occur at 12 weeks, and they will be followed at 6 months as part of an observational cohort whereby the same outcome measures will be recorded. Those who exit the study and are unblinded at early time points (i.e., 4, 8 or 12 weeks in those with a 12-week negative outcome) will be followed as an observational cohort if they received one of the study treatments, including a variation (e.g., a higher dose of ketamine, a left-sided cervical sympathetic blocks). These time points will be the same as in the clinical trial portion of the study (1,2,4,8 and 12 weeks), and 6 months. For those in either the clinical trial extension or observational cohort who continue to experience a positive outcome at 6 months, we will again follow them at 12 months.
192 studies on the registry are indexed under Post-Traumatic Headache; 54 are open to participants now.
This study's planned enrollment of 175 is above the median of 44 across 169 interventional studies indexed under Post-Traumatic Headache.
Browse Post-Traumatic Headache studies →Northwestern University is the lead sponsor of 1,423 studies on the registry; 198 are open to participants now.
Of its 105 completed or terminated interventional studies of FDA-regulated products, 78 (74%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
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.
Procedure: Group A 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.
Drug: Group B active comparator
These patients will receive both SGB with bupivacaine + ketamine as described above.
Combination Product: Group C Experimental
These patients will receive the sham SGB + placebo ketamine as described above.
Other: Group D Placebo Comparator
Group A placebo comparator. Stellate Ganglion Block plus placebo (.9 normal saline) infusion
Also known as: Group A
Active Comparator: Group B = Sham Stellate Ganglion Block plus ketamine infusion
Also known as: Group B
Group C experimental Stellate Ganglion Block plus ketamine infusion
Also known as: Group C
Group D Placebo Comparator: Sham Stellate Ganglion Block plus placebo normal saline
Also known as: Group D
Headache Impact Test (HIT-6)
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.
Time frame: 4 weeks
PTSD Checklist (PCL-5)
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.
Time frame: 4 weeks
Central Sensitization Inventory (CSI)
A 25-item survey which measures central sensitization, 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
Time frame: 1 week after procedure
Central Sensitization Inventory (CSI)
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
Time frame: 2 weeks after procedure
Central Sensitization Inventory (CSI)
A 25-item survey which measures central sensitization, 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
Time frame: 4 weeks after procedure
Central Sensitization Inventory (CSI)
A 25-item survey which measures central sensitization, 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
Time frame: 8 weeks after procedure
Central Sensitization Inventory (CSI)
A 25-item survey which measures central sensitization, 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
Time frame: 12 weeks after procedure
Headache intensity
Average and worst headache scores (0-10 numerical rating scale (NRS), overall pain (0=no pain, 10=worst pain imaginable). NRS scale)
Time frame: 1 week after procedure
Headache intensity
Average and worst headache scores (0-10 numerical rating scale (NRS), overall pain (0=no pain, 10=worst pain imaginable). NRS scale)
Time frame: 2 weeks after procedure
Headache intensity
Average and worst headache scores (0-10 numerical rating scale (NRS), overall pain (0=no pain, 10=worst pain imaginable). NRS scale)
Time frame: 4 weeks after procedure
Headache intensity
Average and worst headache scores (0-10 numerical rating scale (NRS), overall pain (0=no pain, 10=worst pain imaginable). NRS scale)
Time frame: 8 weeks after procedure
Headache intensity
Average and worst headache scores (0-10 numerical rating scale (NRS), overall pain (0=no pain, 10=worst pain imaginable). NRS scale)
Time frame: 12 weeks after procedure
Headache frequency
Days per week with scores greater or equal to 2, and 7/10 (2= mild headache, 7=severe headache)
Time frame: 1 week after procedure
Headache frequency
Days per week with scores greater or equal to 2, and 7/10 (2= mild headache, 7=severe headache)
Time frame: 2 weeks after procedure
Headache frequency
Days per week with scores greater or equal to 2, and 7/10 (2= mild headache, 7=severe headache)
Time frame: 4 weeks after procedure
Headache frequency
Days per week with scores greater or equal to 2, and 7/10 (2= mild headache, 7=severe headache)
Time frame: 8 weeks after procedure
Headache frequency
Days per week with scores greater or equal to 2, and 7/10 (2= mild headache, 7=severe headache)
Time frame: 12 weeks after procedure
Analgesic or psychotropic medication reduction
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).
Time frame: 1 week after procedure
Analgesic or psychotropic medication reduction
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).
Time frame: 2 weeks after procedure
Analgesic or psychotropic medication reduction
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).
Time frame: 4 weeks after procedure
Analgesic or psychotropic medication reduction
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).
Time frame: 8 weeks after procedure
Analgesic or psychotropic medication reduction
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).
Time frame: 12 weeks after procedure
Headache Impact Test (HIT-6)
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.
Time frame: 1 week
Headache Impact Test (HIT-6)
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.
Time frame: 2 weeks
Headache Impact Test (HIT-6)
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.
Time frame: 8 weeks
Headache Impact Test (HIT-6)
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.
Time frame: 12 weeks
Quality of Life after Brain Injury scale (QoLIBRI)
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.
Time frame: 1 week
Quality of Life after Brain Injury scale (QoLIBRI)
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.
Time frame: 2 weeks
Quality of Life after Brain Injury scale (QoLIBRI)
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.
Time frame: 4 weeks
Quality of Life after Brain Injury scale (QoLIBRI)
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.
Time frame: 8 weeks
Quality of Life after Brain Injury scale (QoLIBRI)
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.
Time frame: 12 weeks
Hospital Anxiety and Depression Scale (HADS)
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.
Time frame: 1 week
Hospital Anxiety and Depression Scale (HADS)
Hospital anxiety and depression scale, a 14 question survey scored survey. The anxiety is scored 0 (low) to 21 (high). The depression is scored 0 (low) to 21 (high).
Time frame: 2 weeks after procedure
Hospital Anxiety and Depression Scale (HADS)
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.
Time frame: 4 weeks
Hospital Anxiety and Depression Scale (HADS)
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.
Time frame: 8 weeks
Hospital Anxiety and Depression Scale (HADS)
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.
Time frame: 12 weeks
Patient Global Impression of Change Scale
7-item Likert scale with scores ranging from 0 (worse or no change) to 7 (a great deal better)
Time frame: 1 week
Patient Global Impression of Change Scale
7-item Likert scale with scores ranging from 0 (worse or no change) to 7 (a great deal better)
Time frame: 2 weeks
Patient Global Impression of Change Scale
7-item Likert scale with scores ranging from 0 (worse or no change) to 7 (a great deal better)
Time frame: 4 weeks
Patient Global Impression of Change Scale
7-item Likert scale with scores ranging from 0 (worse or no change) to 7 (a great deal better)
Time frame: 8 weeks
Patient Global Impression of Change Scale
7-item Likert scale with scores ranging from 0 (worse or no change) to 7 (a great deal better)
Time frame: 12 weeks
Positive categorical outcome
Positive is \>/= 4 on the PGIC scale and \>/= 6-point reduction in HIT-6 and/or a \>/= 10-point reduction in PCL-5.
Time frame: 1 week
Positive categorical outcome
Positive is \>/= 4 on the PGIC scale and \>/= 6-point reduction in HIT-6 and/or a \>/= 10-point reduction in PCL-5.
Time frame: 2 weeks
Positive categorical outcome
Positive is \>/= 4 on the PGIC scale and \>/= 6-point reduction in HIT-6 and/or a \>/= 10-point reduction in PCL-5.
Time frame: 4 weeks
Positive categorical outcome
Positive is \>/= 4 on the PGIC scale and \>/= 6-point reduction in HIT-6 and/or a \>/= 10-point reduction in PCL-5.
Time frame: 8 weeks
Positive categorical outcome
Positive is \>/= 4 on the PGIC scale and \>/= 6-point reduction in HIT-6 and/or a \>/= 10-point reduction in PCL-5.
Time frame: 12 weeks
Sheehan Suicidality Tracking Scale (S-STS)
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.
Time frame: 4 weeks after procedure
International Trauma Questionnaire
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.
Time frame: 4 weeks
International Trauma Questionnaire
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.
Time frame: 12 weeks
PCL-5
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.
Time frame: 1 week
PCL-5
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.
Time frame: 2 weeks
PCL-5
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.
Time frame: 8 weeks
PCL-5
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.
Time frame: 12 weeks
PTSD Checklist (PCL-5)
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.
Time frame: 1 week
PTSD Checklist (PCL-5)
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.
Time frame: 2 weeks
PTSD Checklist (PCL-5)
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.
Time frame: 8 weeks
PTSD Checklist (PCL-5)
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.
Time frame: 12 weeks
Quantitative sensory testing
Quantitative sensory testing will include mechanical temporal summation, a measure of central sensitization, pressure pain thresholds, and the simultaneous presentation of 2 stimuli to assess intrinsic modulation, known as conditioned pain modulation. This test is optional
Time frame: 4 weeks after procedure
Serum biomarkers
Markers of inflammation to include interleukins 1 and 6 (IL1 and 6), tumor necrosis factor-alpha (TNF), C-reactive protein (CRP), nerve growth factor (NGF), brain-derived neutrotrophic factor (BDNF), Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP). This test is optional.
Time frame: 4 weeks after procedure
Structural MRI Imaging
Volumetric changes in gray and white matter, in different regions. This test is optional.
Time frame: 4 weeks after procedure
Functional MRI
Functional changes in pain and emotion processing centers (e.g., activation of brainstem, thalamus, hippocampus, insula, anterior cingulate, and somatosensory cortices) as well as changes in connectivity between regions. This test is optional.
Time frame: 4 weeks after procedure
Started Jul 2025 (actual). Primary completion is estimated for Dec 2027, 29 months after the start.
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