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Ketamine, SGB and Combination Treatment for TBI-associated Headache or PTSD

ConditionsPosttraumatic HeadachePosttraumatic Stress Disorder
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorNorthwestern University

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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)

Trial design

Design model

Parallel

Treatments tested in this trial

  • Group A active comparator

    Procedure/Surgery

    Group A placebo comparator. Stellate Ganglion Block plus placebo (.9 normal saline) infusion

  • Group B active comparator

    Drug

    Active Comparator: Group B = Sham Stellate Ganglion Block plus ketamine infusion

  • Group C Experimental

    Combination product

    Group C experimental Stellate Ganglion Block plus ketamine infusion

  • Group D Placebo Comparator

    Other intervention

    Group D Placebo Comparator: Sham Stellate Ganglion Block plus placebo normal saline

Treatment groups

175 Participants
are divided into 4 treatment groups
Group A: Group A =Stellate ganglion block (SGB) with bupivacaine (LA) plus placebo ketamine (midazolam)Active comparator 1 intervention
Group B: Group B = Sham SGB plus ketamine infusionActive comparator 1 intervention
Group C: Group C = Stellate ganglion block (SGB) with bupivacaine LA plus ketamine infusionExperimental treatment 1 intervention
Group D: Group D = Sham SGB plus placebo ketamine (midazolam)Placebo comparator 1 intervention

Trial outcomes

Primary outcomes

1

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
2

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

Secondary outcomes

1

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
2

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
3

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
4

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

Other outcomes

1

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
2

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
3

Structural MRI Imaging

Volumetric changes in gray and white matter, in different regions. This test is optional.

Time frame
4 weeks after procedure
4

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

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Northwestern University

Lead sponsor

Walter Reed National Military Medical Center

Collaborator

Lviv National Medical University

Collaborator

Womack Army Medical Center

Collaborator

Source ClinicalTrials.gov
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