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

NCT06608277 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: STU00221519
• Study Type: interventional
• Target: 175
• Locations: 1 country
• Sites: 3

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. 1.To determine the efficacy of SGB and ketamine infusion as stand-alone treatments for TBI-related headache;
2. 2.To determine the efficacy of SGB and ketamine infusion as stand-alone treatments for PTSD;
3. 3.To determine the comparative effectiveness of SGB and ketamine infusion, and the effect of combination treatment on TBI-related headache and PTSD;
4. 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. 5.Exploratory Aim 2: To identify factors associated with treatment responders overall and for individual treatment groups.
6. 6.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).
7. 7.Exploratory Aim 2: To identify factors associated with treatment responders overall and for individual treatment groups.

Conditions

Posttraumatic Headache; Posttraumatic Stress Disorder

Keywords

Ketamine; Stellate Ganglion Block

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  4 weeks

Secondary Outcomes (55)

• Central Sensitization Inventory (CSI)

  1 week after procedure

• Central Sensitization Inventory (CSI)

  2 weeks after procedure

• Central Sensitization Inventory (CSI)

  4 weeks after procedure

• Central Sensitization Inventory (CSI)

  8 weeks after procedure

• Central Sensitization Inventory (CSI)

  12 weeks after procedure

Other Outcomes (4)

• Quantitative sensory testing

  4 weeks after procedure

• Serum biomarkers

  4 weeks after procedure

• Structural MRI Imaging

  4 weeks after procedure

Study Arms (4)

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

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.

Procedure: Group A active comparator

Group B = Sham SGB plus ketamine infusion

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

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

EXPERIMENTAL

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

Combination Product: Group C Experimental

Group D = Sham SGB plus placebo ketamine (midazolam)

PLACEBO COMPARATOR

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

Other: Group D Placebo Comparator

Interventions

Group A active comparator PROCEDURE

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

Also known as: Group A

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

Group B active comparator DRUG

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

Also known as: Group B

Group B = Sham SGB plus ketamine infusion

Group C Experimental COMBINATION_PRODUCT

Group C experimental Stellate Ganglion Block plus ketamine infusion

Also known as: Group C

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

Group D Placebo Comparator OTHER

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

Also known as: Group D

Group D = Sham SGB plus placebo ketamine (midazolam)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Northwestern University: lead
• Lviv National Medical University: collaborator
• Womack Army Medical Center: collaborator
• Walter Reed National Military Medical Center: collaborator

Study Sites (3)

Anesthesiology Pain Medicine Center

Chicago, Illinois, 60611, United States

RECRUITING

Walter Reed National Military Medical Center

Bethesda, Maryland, 20889, United States

RECRUITING

Womack Army Medical Center

Fort Bragg, North Carolina, 28310, United States

NOT YET RECRUITING

MeSH Terms

Conditions

Post-Traumatic Headache; Stress Disorders, Post-Traumatic

Condition Hierarchy (Ancestors)

Headache Disorders, Secondary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Study Officials

• Steven Cohen, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jordan Wood, BS

CONTACT

312-695-0915; jordan.wood1@northwestern.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Participant and outcomes assessor will be blinded to the study group received.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Multi-Center, Randomized, Double-Blind, Placebo-Controlled Trial

Study Record Dates

• First Submitted: September 18, 2024
• First Posted: September 23, 2024
• Study Start: July 2, 2025
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): April 30, 2028
• Last Updated: May 1, 2026

Record last verified: 2026-04

Locations

US (3)