Clinical trial NCT06608277: Ketamine, SGB and Combination Treatment for TBI
Official title: Multi-Center, Randomized, Double-Blind, Placebo-Controlled Trial Comparing Ketamine, Stellate Ganglion Blocks and Combination Treatment to Sham Therapies for Traumatic Brain Injury-Associated Headaches and Post-Traumatic Stress Disorder
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Posttraumatic Headache
Posttraumatic Stress Disorder
Keywords: Ketamine
Stellate Ganglion Block
Lead sponsor: Northwestern University
Sponsor class: OTHER
Collaborators: name: Walter Reed National Military Medical Center
name: Lviv National Medical University
First posted: 2024-09-23
Enrollment: 175
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multi-Center, Randomized, Double-Blind, Placebo-Controlled Trial
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Adults 18 years or older
2. Stable doses of medications for \> 2 weeks for TBI and/or PTSD
3. 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.
4. Duration of chronic TBI or PTSD \> 3 months

Exclusion Criteria:

1. Ketamine infusion or SGB within the past 6 months
2. Serious medical or psychiatric conditions other than TBI or PTSD that could affect cognition (e.g., dementia, Parkinson's Disease)
3. Elevated intracranial pressure
4. For TBI, prior history of headache that can explain the headache intensity (i.e., headache not attributable to TBI)
5. Active psychosis or poorly controlled non-injury or PTSD-related psychiatric condition (e.g., bipolar disorder)
6. Poorly controlled medical conditions that could be exacerbated by treatment (e.g., unstable angina)
7. Pregnancy (women of childbearing age who can become pregnant will have to take a pregnancy test)
8. Non-fluency in English (poor generalizability to military and veteran populations, instruments not validated for use or translated in many languages)

Primary outcomes:
measure: Headache Impact Test (HIT-6)
timeFrame: 4 weeks
measure: PTSD Checklist (PCL-5)
timeFrame: 4 weeks
Secondary outcomes:
measure: Central Sensitization Inventory (CSI)
timeFrame: 4 weeks after procedure
measure: Central Sensitization Inventory (CSI)
timeFrame: 12 weeks after procedure
measure: Headache intensity
timeFrame: 4 weeks after procedure
measure: Headache intensity
timeFrame: 8 weeks after procedure
measure: Headache intensity
timeFrame: 12 weeks after procedure
measure: Headache frequency
timeFrame: 4 weeks after procedure
measure: Headache frequency
timeFrame: 8 weeks after procedure
measure: Hospital Anxiety and Depression Scale (HADS)
timeFrame: 12 weeks after procedure
measure: Analgesic or psychotropic medication reduction
timeFrame: 4 weeks after procedure
measure: Analgesic or psychotropic medication reduction
timeFrame: 8 weeks after procedure
measure: Analgesic or psychotropic medication reduction
timeFrame: 12 weeks after procedure
measure: Headache Impact Test (HIT-6)
timeFrame: 8 weeks
measure: Headache Impact Test (HIT-6)
timeFrame: 12 weeks
measure: Quality of Life after Brain Injury scale (QoLIBRI)
timeFrame: 4 weeks
measure: Quality of Life after Brain Injury scale (QoLIBRI)
timeFrame: 8 weeks
measure: Quality of Life after Brain Injury scale (QoLIBRI)
timeFrame: 12 weeks
measure: Hospital Anxiety and Depression Scale (HADS)
timeFrame: 4 weeks
measure: Hospital Anxiety and Depression Scale (HADS)
timeFrame: 8 weeks
measure: Hospital Anxiety and Depression Scale (HADS)
timeFrame: 12 weeks
measure: Patient Global Impression of Change Scale
timeFrame: 4 weeks
measure: Patient Global Impression of Change Scale
timeFrame: 8 weeks
measure: Patient Global Impression of Change Scale
timeFrame: 12 weeks
measure: Positive categorical outcome
timeFrame: 4 weeks
measure: Positive categorical outcome
timeFrame: 8 weeks
measure: Positive categorical outcome
timeFrame: 12 weeks
measure: Central Sensitization Inventory (CSI)
timeFrame: 8 weeks after procedure
measure: Sheehan Suicidality Tracking Scale (S-STS)
timeFrame: 4 weeks after procedure
measure: Sheehan Suicidality Tracking Scale (S-STS)
timeFrame: 8 weeks after procedure
measure: Sheehan Suicidality Tracking Scale (S-STS)
timeFrame: 12 weeks after procedure
measure: International Trauma Questionnaire
timeFrame: 4 weeks
measure: International Trauma Questionnaire
timeFrame: 12 weeks
Other outcomes:
measure: Quantitative sensory testing
timeFrame: 4 weeks after procedure
measure: Serum biomarkers
timeFrame: 4 weeks
Locations:
city: Chicago
country: United States
facility: Anesthesiology Pain Medicine Center
state: Illinois
city: Bethesda
country: United States
facility: Walter Reed National Military Medical Center
state: Maryland
city: Lviv
country: Ukraine
facility: First Medical Union
state: Lviv Oblast
Study officials:
affiliation: Northwestern University
name: Steven Cohen, MD
role: PRINCIPAL_INVESTIGATOR
References: