Ketamine and SGB for Traumatic Brain Injury

Recruiting at 3 trial locations

Overseen By Paul Fitzgerald, RN,BSN,MS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Northwestern University

Disqualifiers: Dementia, Parkinson's, Bipolar, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 8

Duration: 4 weeks

175 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a nerve block procedure (Stellate Ganglion Block, or SGB) or the medication ketamine, alone or combined, can help individuals with PTSD and headaches from traumatic brain injuries (TBI). Researchers aim to determine which treatment best eases symptoms and improves daily life. Individuals with TBI or PTSD for more than 3 months and on stable medication for over 2 weeks may be suitable for this study. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it requires that your medication doses have been stable for more than two weeks for TBI and/or PTSD.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the stellate ganglion block (SGB) is generally safe and well-tolerated for treating PTSD. Studies have found that patients experience few complications, especially when doctors use imaging tools like ultrasound to guide the procedure. This guidance ensures accuracy and reduces the risk of side effects.

Regarding ketamine, studies indicate it does not harm patients with traumatic brain injury (TBI). Specifically, research suggests that ketamine may help lower intracranial pressure, benefiting those with TBI. Overall, ketamine appears safe for use in TBI patients.

Both treatments, SGB and ketamine, have undergone safety studies and seem well-tolerated by patients with the conditions under investigation. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for traumatic brain injury (TBI) because they combine innovative approaches that could offer faster and possibly more effective relief than current options. Unlike traditional treatments that mainly focus on managing symptoms with medications like painkillers or anti-seizure drugs, the investigational use of ketamine and stellate ganglion block (SGB) targets the underlying neural pathways affected by TBI. Ketamine, known for its rapid-acting antidepressant effects, is being used here for its potential to reduce brain inflammation and improve neural function. SGB, typically used for pain relief, is being explored for its ability to regulate the autonomic nervous system and promote brain recovery. This combination could provide a new avenue for treatment that addresses both the physical and emotional impacts of TBI.

What evidence suggests that this trial's treatments could be effective for TBI-related headache and PTSD?

Research has shown that both stellate ganglion block (SGB) and ketamine may assist with PTSD and TBI-related issues. SGB consistently reduces PTSD symptoms, with improvements ranging from 5.4% to 21.2% after repeated treatments. It also alleviates trauma symptoms, achieving success rates over 70% in various studies. Ketamine may lower brain pressure in TBI patients, which can aid in managing brain injury symptoms. In this trial, participants will receive one of the following: SGB with bupivacaine plus placebo ketamine, sham SGB plus ketamine infusion, SGB with bupivacaine plus ketamine infusion, or sham SGB plus placebo ketamine. These treatments, whether used alone or in combination, are being studied for their potential to enhance the quality of life for individuals with these conditions. ^{2 3 4 6 7}

Who Is on the Research Team?

Steven Cohen, MD

Principal Investigator

Northwestern University

Are You a Good Fit for This Trial?

This trial is for individuals with PTSD and TBI-related headaches, common in military personnel from recent conflicts. Participants should have these conditions to qualify but the full inclusion and exclusion criteria are not provided here.

Inclusion Criteria

My medication doses for TBI or PTSD have been stable for more than 2 weeks.

I have severe headaches or PTSD with specific test scores.

I have had TBI or PTSD for more than 3 months.

Exclusion Criteria

I do not have active psychosis or unmanaged mental health conditions like bipolar disorder.

I do not have conditions like dementia or Parkinson's affecting my thinking.

I do not have any health conditions that could worsen with treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either stellate ganglion block (SGB), ketamine infusion, or a combination treatment for PTSD and TBI-associated headaches

4 weeks

Weekly visits for treatment administration

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at 8 and 12 weeks

8 weeks

Follow-up visits at 8 and 12 weeks

Observational Cohort

Participants with negative outcomes exit the study and are followed as an observational cohort, eligible for non-study measures

Ongoing

What Are the Treatments Tested in This Trial?

Interventions

• Group C Experimental
• Ketamine
• Stellate Ganglion Block (SGB)

Trial Overview

The study tests if a nerve block procedure (SGB) or ketamine medication, alone or combined, can relieve PTSD and headache symptoms from TBI. It's a randomized, double-blind, placebo-controlled trial across multiple centers.

How Is the Trial Designed?

Group I: Group C = Stellate ganglion block (SGB) with bupivacaine LA plus ketamine infusion Experimental Treatment 1 Intervention

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

Group II: Group A =Stellate ganglion block (SGB) with bupivacaine (LA) plus placebo ketamine (midazolam) Active Control 1 Intervention

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 III: Group B = Sham SGB plus ketamine infusion Active Control 1 Intervention

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 IV: Group D = Sham SGB plus placebo ketamine (midazolam) Placebo Group 1 Intervention

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

Who Is Running the Clinical Trial?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

Walter Reed National Military Medical Center

Collaborator

Trials

149

Recruited

33,800+

Lviv National Medical University

Collaborator

Trials

9

Recruited

1,300+

Womack Army Medical Center

Collaborator

Trials

22

Recruited

17,100+

Published Research Related to This Trial

Grapefruit juice significantly increases the plasma levels of oral S-ketamine, with a 3-fold increase in the area under the plasma concentration-time curve and a 2.1-fold increase in peak plasma concentration, indicating a strong interaction that could affect dosing.

Due to the increased plasma concentrations, it is recommended that dose reductions of S-ketamine be considered when taken with grapefruit juice to avoid potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

S-ketamine concentrations are greatly increased by grapefruit juice. Peltoniemi, MA., Saari, TI., Hagelberg, NM., et al.[2021]

In a study using rat models of traumatic brain injury caused by maxillofacial impact, ketamine treatment significantly improved recovery time, with treated rats recovering about 2 days faster than the control group.

The results suggest that ketamine may be an effective intervention for enhancing recovery following traumatic brain injuries, indicating its potential therapeutic role in similar human injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Animal experiment of the ketamine effects on traumatic brain injury resulting from impact maxillofacial injury]. Zhang, C., Li, H., Liao, W., et al.[2013]

Ketamine can be safely used in patients with neurological impairments when administered under controlled conditions, as it does not increase intracranial pressure and may improve cerebral perfusion.

In addition to its safety profile, ketamine shows neuroprotective effects in laboratory settings, suggesting potential benefits for brain injury recovery, although caution is needed due to possible neurotoxic effects at high doses in certain animal studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Revising a dogma: ketamine for patients with neurological injury? Himmelseher, S., Durieux, ME.[2022]

Subcutaneous (SC) administration of racemic ketamine and esketamine has shown rapid and robust antidepressant effects in both unipolar and bipolar patients, with response and remission rates ranging from 50% to 100% after single or multiple doses.

The studies indicated that SC ketamine is generally well-tolerated, with only transitory side effects, making it a promising and cost-effective treatment option for depression, especially in developing countries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous Ketamine in Depression: A Systematic Review. Cavenaghi, VB., da Costa, LP., Lacerda, ALT., et al.[2021]

Ketamine is a promising medication for managing sedation and pain in patients with traumatic brain injury (TBI), as it does not increase intracranial pressure and may even lower it.

Its favorable safety profile makes ketamine a reliable option for use in prehospital settings during the acute phase of TBI, although careful consideration of its benefits and potential drawbacks is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine in acute phase of severe traumatic brain injury "an old drug for new uses?" Godoy, DA., Badenes, R., Pelosi, P., et al.[2021]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11540192/

Clinical outcomes of ketamine in patients with traumatic ...

Four studies indicated a statistically significant decline in ICP in TBI patients, with ketamine sedation. Contrastingly, two studies revealed ...

2.

jtraumainj.org

jtraumainj.org/journal/view.php?number=1271

Outcomes and physiologic responses associated with ...

Purpose: Ketamine has historically been contraindicated in traumatic brain injury (TBI) due to concern for raising intracranial pressure.

3.

ccforum.biomedcentral.com

ccforum.biomedcentral.com/articles/10.1186/s13054-020-03452-x

Ketamine in acute phase of severe traumatic brain injury “an ...

Current evidence shows that ketamine does not increase and may instead decrease intracranial pressure, and its safety profile makes it a reliable tool in the ...

4.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05097261

NCT05097261 | Ketamine in Acute Brain Injury Patients.

The primary efficacy endpoint will be the reduction in daily Therapy Intensity Level (TIL) score, based on the highest score in each item per day until study ...

5.

liebertpub.com

liebertpub.com/doi/full/10.1089/neur.2024.0146

High-Frequency Analysis of the Cerebral Physiological ...

Results indicated higher median ICP in the ketamine group compared with the no ketamine group (9.05 mmHg and 14.00 mmHg, respectively, p = ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8949520/

Ketamine in Acute Brain Injury: Current Opinion Following ...

There was no evidence of harm from the ketamine's use in patients with TBI. Keywords: ketamine, acute brain injury, trauma brain injury, ...

7.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/41197253/

Is ketamine safe for traumatic brain injury? A systematic ...

Historically, ketamine has been associated with increased intracranial pressure (ICP), raising concerns about its use in TBI patients and ...