Ketamine for Aortic Aneurysm Pain Management

(2020Ketamine Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Samuel Tyagi, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Sam Tyagi

Must be taking: Naloxone

Disqualifiers: Schizophrenia, Hydrocephalus, Pregnancy, others

Prior Safety Data

Approved in 5 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing low doses of ketamine to see if it can reduce pain and the need for opioids in patients having a specific type of heart surgery. These patients usually need a lot of pain relief because they are also getting another treatment to prevent a serious complication. Ketamine works by blocking pain signals in the brain. Ketamine is an old anesthetic agent that has been explored for pain relief in various conditions, including cancer pain and acute pain episodes.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What evidence supports the effectiveness of the drug ketamine for pain management in aortic aneurysm patients?

Research shows that ketamine, especially in its S-ketamine form, can effectively reduce pain in various surgical settings, such as after knee surgery and hysterectomy. This suggests it might also help manage pain in aortic aneurysm patients. ^{1 2 3 4 5}

How does ketamine differ from other drugs for aortic aneurysm pain management?

Ketamine is unique for aortic aneurysm pain management because it is primarily known as an anesthetic and pain reliever that works by blocking NMDA receptors in the brain, which is different from other treatments that focus on slowing aneurysm growth or reducing inflammation. This makes ketamine potentially useful for immediate pain relief rather than altering the progression of the aneurysm itself. ^{6 7 8 9 10}

Research Team

Samuel Tyagi, MD

Principal Investigator

University of Kentucky

Anna Rockich, Pharm D

Principal Investigator

University of Kentucky

Eligibility Criteria

This trial is for individuals scheduled for elective repair of the thoracic or thoracoabdominal aorta who need naloxone infusion for spinal protection. It's not open to those allergic to ketamine, acetaminophen, or fentanyl; diagnosed with schizophrenia; with hydrocephalus or CNS mass; incarcerated persons; or pregnant/lactating individuals.

Inclusion Criteria

I am scheduled for surgery on the main artery in my chest or belly.

I need a continuous naloxone infusion for spinal protection.

Willing to give informed consent

Exclusion Criteria

I have been diagnosed with schizophrenia.

I have had hydrocephalus or a brain tumor.

I am allergic to ketamine, acetaminophen, or fentanyl.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either sub-dissociative ketamine or placebo during and for 48 hours post TEVAR procedure

48 hours

Continuous monitoring during hospital stay

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Ketamine (NMDA Receptor Antagonist)

Trial Overview The study aims to see if low-dose ketamine can reduce pain and lessen opioid use in patients having TEVAR procedures while on naloxone infusion. Participants will receive either saline (a placebo) or ketamine alongside standard care.

Participant Groups

Group I: Sub-Dissociative Ketamine Experimental Treatment 1 Intervention

Participants in this group will receive standard of care as well as a continuous ketamine infusion at the induction of anesthesia and for 48 hours postoperatively.

Group II: Standard of Care Placebo Group 1 Intervention

Participants in this group will receive standard of care as well as a saline infusion during the study period.

Who Is Running the Clinical Trial?

Sam Tyagi

Lead Sponsor

Trials

1

Recruited

20+

Anna Rockich

Lead Sponsor

Trials

3

Recruited

30+

Findings from Research

In a study of 69 gynecological surgery patients, low dose ketamine (0.15 mg/Kg) administered preoperatively did not provide a preemptive analgesic effect, as indicated by similar pain scores at rest compared to placebo.

However, patients receiving ketamine postoperatively experienced less pain upon movement on the fifth day and required less morphine in the first 6 hours, suggesting that while preemptive use is ineffective, postoperative ketamine can still improve pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effect of low-dose intravenous ketamine in postoperative analgesia for hysterectomy and adnexectomy]. Gilabert Morell, A., Sánchez Pérez, C.[2013]

Oral ketamine has shown effectiveness in treating severe depression, including treatment-resistant cases and those with suicidal ideation, based on various studies including randomized controlled trials with doses ranging from 0.25 to 7 mg/kg.

Despite its lower bioavailability (20%-25% reaching the bloodstream), oral ketamine is well tolerated and can be adjusted for individual needs, making it a practical option for depression treatment alongside conventional antidepressants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral Ketamine for Depression, 1: Pharmacologic Considerations and Clinical Evidence. Andrade, C.[2019]

S(+)-Ketamine, at half the dose of ketamine racemate, provides similar analgesic effects while causing fewer adverse effects on cognitive functions and a smaller increase in heart rate, making it a promising option for emergency medicine.

In a study involving 16 healthy volunteers, S(+)-ketamine resulted in significantly less anterograde amnesia compared to ketamine racemate, suggesting it may be safer for use in situations where maintaining cognitive function is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Psychometric changes as well as analgesic action and cardiovascular adverse effects of ketamine racemate versus s-(+)-ketamine in subanesthetic doses]. Pfenninger, E., Baier, C., Claus, S., et al.[2013]

In a study of 50 patients undergoing knee surgery, a single intraoperative dose of ketamine significantly reduced postoperative pain and the need for additional pain medication compared to a placebo.

Patients receiving ketamine were able to walk longer on the first postoperative day, indicating improved functional outcomes alongside enhanced pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraoperative small-dose ketamine enhances analgesia after outpatient knee arthroscopy. Menigaux, C., Guignard, B., Fletcher, D., et al.[2019]

Several medications, including statins and doxycycline, may help prevent the expansion of abdominal aortic aneurysms by targeting inflammation in the aortic wall, based on various studies.

Despite promising results from animal and observational studies, there is a lack of randomized clinical trials to firmly establish the efficacy of these treatments, indicating a need for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can pharmacologic agents slow abdominal aortic aneurysm growth? Samson, R.[2012]

Alpha-ketoglutarate (AKG) significantly prevents the formation and progression of abdominal aortic aneurysms (AAA) in mouse models by reducing aneurysmal dilation and aortic rupture, indicating its potential as a therapeutic agent.

AKG works by inhibiting oxidative stress and inflammation, as evidenced by decreased inflammatory cytokines and reduced macrophage infiltration, suggesting that it regulates key signaling pathways involved in AAA development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alpha-ketoglutarate ameliorates abdominal aortic aneurysm via inhibiting PXDN/HOCL/ERK signaling pathways. Liu, J., Liu, M., Feng, J., et al.[2022]

Vitamin D deficiency in a mouse model led to larger and more rupture-prone abdominal aortic aneurysms (AAAs), with a rupture rate of 48% compared to 19% in controls, indicating a significant role in AAA development.

Administering cholecalciferol (CCF) to mice with established AAAs reduced their growth and rupture rate (8% vs. 46%), suggesting that vitamin D supplementation could be a potential therapeutic strategy, likely through its effects on genes involved in extracellular matrix remodeling.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vitamin D deficiency promotes large rupture-prone abdominal aortic aneurysms and cholecalciferol supplementation limits progression of aneurysms in a mouse model. Nsengiyumva, V., Krishna, SM., Moran, CS., et al.[2021]

Currently, there is no effective medical therapy available to prevent the progression of aortic aneurysm (AA), despite various pharmacological agents like β-blockers and angiotensin inhibitors being investigated.

The review highlights the gap between successful preclinical studies and clinical failures, emphasizing the need for better understanding of AA's pathophysiology to identify new therapeutic targets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current Pharmacological Management of Aortic Aneurysm. Xiang, B., Zhu, S., Li, J., et al.[2022]

In a study using apolipoprotein E-deficient mice, activation of the kinin B2 receptor (B2R) was found to promote aortic rupture in abdominal aortic aneurysm (AAA) models, linked to increased neutrophil infiltration and inflammation.

Conversely, using a B2R antagonist provided protection against aortic rupture and reduced aneurysm growth, suggesting that targeting B2R signaling could be a promising therapeutic strategy for AAA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modulation of Kinin B2 Receptor Signaling Controls Aortic Dilatation and Rupture in the Angiotensin II-Infused Apolipoprotein E-Deficient Mouse. Moran, CS., Rush, CM., Dougan, T., et al.[2018]

References

1. United States pubmed.ncbi.nlm.nih.gov

Use of Various Doses of S-Ketamine in Treatment of Depression and Pain in Cervical Carcinoma Patients with Mild/Moderate Depression After Laparoscopic Total Hysterectomy. [2021]

2. Spain pubmed.ncbi.nlm.nih.gov

[Effect of low-dose intravenous ketamine in postoperative analgesia for hysterectomy and adnexectomy]. [2013]

3. United States pubmed.ncbi.nlm.nih.gov

Oral Ketamine for Depression, 1: Pharmacologic Considerations and Clinical Evidence. [2019]

4. Germany pubmed.ncbi.nlm.nih.gov

[Psychometric changes as well as analgesic action and cardiovascular adverse effects of ketamine racemate versus s-(+)-ketamine in subanesthetic doses]. [2013]

5. United States pubmed.ncbi.nlm.nih.gov

Intraoperative small-dose ketamine enhances analgesia after outpatient knee arthroscopy. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Can pharmacologic agents slow abdominal aortic aneurysm growth? [2012]

7. England pubmed.ncbi.nlm.nih.gov

Alpha-ketoglutarate ameliorates abdominal aortic aneurysm via inhibiting PXDN/HOCL/ERK signaling pathways. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Vitamin D deficiency promotes large rupture-prone abdominal aortic aneurysms and cholecalciferol supplementation limits progression of aneurysms in a mouse model. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Current Pharmacological Management of Aortic Aneurysm. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Modulation of Kinin B2 Receptor Signaling Controls Aortic Dilatation and Rupture in the Angiotensin II-Infused Apolipoprotein E-Deficient Mouse. [2018]