Ketamine, SGB and Combination Treatment for TBI

NCT ID: NCT06608277

Last Updated: 2025-08-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

175 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-07-02

Study Completion Date

2028-04-30

Brief Summary

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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

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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.

Conditions

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Posttraumatic Headache Posttraumatic Stress Disorder

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Multi-Center, Randomized, Double-Blind, Placebo-Controlled Trial
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Outcome Assessors
Participant and outcomes assessor will be blinded to the study group received.

Study Groups

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Group A =Stellate ganglion block (SGB) with bupivacaine (LA) plus placebo ketamine (midazolam)

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 Type ACTIVE_COMPARATOR

Group A active comparator

Intervention Type PROCEDURE

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

Group B = Sham SGB plus ketamine infusion

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 Type ACTIVE_COMPARATOR

Group B active comparator

Intervention Type DRUG

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

Group C = Stellate ganglion block (SGB) with bupivacaine LA plus ketamine infusion

These patients will receive both SGB with bupivacaine + ketamine as described above.

Group Type EXPERIMENTAL

Group C Experimental

Intervention Type COMBINATION_PRODUCT

Group C experimental Stellate Ganglion Block plus ketamine infusion

Group D = Sham SGB plus placebo ketamine (midazolam)

These patients will receive the sham SGB + placebo ketamine as described above.

Group Type PLACEBO_COMPARATOR

Group D Placebo Comparator

Intervention Type OTHER

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

Interventions

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Group A active comparator

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

Intervention Type PROCEDURE

Group B active comparator

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

Intervention Type DRUG

Group C Experimental

Group C experimental Stellate Ganglion Block plus ketamine infusion

Intervention Type COMBINATION_PRODUCT

Group D Placebo Comparator

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

Intervention Type OTHER

Other Intervention Names

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Group A Group B Group C Group D

Eligibility Criteria

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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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Walter Reed National Military Medical Center

FED

Sponsor Role collaborator

Lviv National Medical University

OTHER

Sponsor Role collaborator

Womack Army Medical Center

FED

Sponsor Role collaborator

Northwestern University

OTHER

Sponsor Role lead

Responsible Party

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Steven Cohen

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Steven Cohen, MD

Role: PRINCIPAL_INVESTIGATOR

Northwestern University

Locations

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Anesthesiology Pain Medicine Center

Chicago, Illinois, United States

Site Status RECRUITING

Walter Reed National Military Medical Center

Bethesda, Maryland, United States

Site Status NOT_YET_RECRUITING

Womack Army Medical Center

Fort Bragg, North Carolina, United States

Site Status NOT_YET_RECRUITING

Countries

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United States

Central Contacts

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Paul Fitzgerald, RN,BSN,MS

Role: CONTACT

312-695-1064

Facility Contacts

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Jordan Wood

Role: primary

312-695-0915

Stacey Harcum, MS, MPH

Role: primary

240-956-8199

Min H Chang, MD

Role: primary

910-643-2310

Other Identifiers

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STU00221519

Identifier Type: -

Identifier Source: org_study_id

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