Ketamine, stellate ganglion block, or both for TBI-related headache and PTSD

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

Phase 2 Interventional Northwestern University · NCT06608277

This trial will try ketamine infusions, a stellate ganglion block, or both to see if they reduce headaches and PTSD symptoms in adults with traumatic brain injury and/or PTSD.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment175 (estimated)
Ages18 Years and up
SexAll
SponsorNorthwestern University Academic / other
Locations3 sites (Chicago, Illinois and 2 other locations)
Trial IDNCT06608277 on ClinicalTrials.gov

What this trial studies

This is a multicenter, randomized, double-blind, placebo-controlled Phase 2 trial that will enroll about 175 adults and randomize them into four groups in a 2:2:2:1 ratio to receive ketamine, stellate ganglion block (SGB), the combination, or sham/placebo. The primary outcomes are patient-reported headache and PTSD measures collected at baseline and the primary endpoint at 4 weeks, with additional assessments at 1 and 2 weeks and extended follow-up for responders at 8 and 12 weeks. Several quality-of-life and symptom instruments (including HIT-6 and PCL-5) will be used to measure treatment effect, and responders who do not improve will be followed observationally for alternative care. The trial aims to identify not only whether these therapies work but which patient factors predict better outcomes to inform more personalized treatment choices.

Who should consider this trial

Good fit: Adults aged 18 or older with chronic post-traumatic headache and/or PTSD of more than three months' duration who meet screening thresholds on HIT-6 or PCL-5 and are on stable medication doses are ideal candidates.

Not a fit: People with recent ketamine or SGB within six months, active psychosis, serious non-TBI cognitive disorders, elevated intracranial pressure, or headaches explained by another diagnosis are unlikely to be eligible or to benefit from this protocol.

Why it matters

Potential benefit: If effective, these interventions could reduce headache severity and PTSD symptoms and improve quality of life for people with chronic TBI-related headache and/or PTSD.

How similar studies have performed: Early and small studies and case reports have suggested benefit from both ketamine and SGB for PTSD and post-traumatic headache, but results are preliminary and sometimes conflicting.

Eligibility criteria

Show full inclusion / exclusion 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)

Where this trial is running

Chicago, Illinois and 2 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Posttraumatic HeadachePosttraumatic Stress DisorderKetamineStellate Ganglion Block
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.