Ketamine + Midazolam for Complex Regional Pain Syndrome

Overseen By Theresa R Lii, MD, MS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Stanford University

Disqualifiers: Age, English comprehension, others

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

Compensation: Varies

Number of Visits: 5

Duration: 1 week

Trial Summary

What is the purpose of this trial?

This trial is testing whether a combination of ketamine and midazolam or just midazolam alone can help adults with CRPS. CRPS patients are targeted because they suffer from severe, chronic pain that is hard to treat. Ketamine works by reducing pain through brain receptors, while midazolam helps with anxiety. Midazolam has been used in combination with ketamine for various medical procedures to improve sedation and pain management.

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 data supports the effectiveness of the drug Ketamine + Midazolam for treating Complex Regional Pain Syndrome?

Research shows that ketamine, often used with midazolam to reduce side effects, can be effective for treating complex regional pain syndrome, especially when other treatments have failed. Studies have found that ketamine helps reduce severe pain and improve symptoms in patients with this condition. ^{1 2 3 4 5}

Is the combination of ketamine and midazolam safe for treating complex regional pain syndrome?

Research indicates that ketamine, when used with midazolam, has not led to serious complications in treating complex regional pain syndrome, thanks to careful psychological screening and the use of additional medications to manage side effects. ^{1 2 3 6 7}

How is the drug combination of Ketamine and Midazolam unique for treating Complex Regional Pain Syndrome?

The combination of Ketamine and Midazolam is unique for treating Complex Regional Pain Syndrome because Ketamine blocks NMDA receptors involved in pain transmission, while Midazolam helps counteract potential psychological side effects of Ketamine, making it effective when standard treatments have failed. ^{1 3 5 7 8}

Research Team

Theresa R Lii, MD, MS

Principal Investigator

Stanford University

Eligibility Criteria

Adults aged 18-65 with Complex Regional Pain Syndrome (CRPS) who've had pain for at least 3 months, can understand English questionnaires, and have a reliable adult to provide transportation during the trial. They must not be part of any group specifically excluded by the study's criteria.

Inclusion Criteria

I have had pain from CRPS for 3 months or more.

My average pain level has been 3 or higher in the past month.

You have been diagnosed with complex regional pain syndrome (CRPS) according to specific guidelines.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intravenous infusions of ketamine and midazolam or midazolam and saline for 4 hours each day, over 5 consecutive days, in an outpatient setting

1 week

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

Weekly assessments

Treatment Details

Interventions

• Ketamine and Midazolam Infusions

Trial Overview The study is testing if it's feasible to give adults with CRPS either ketamine plus midazolam or just midazolam alone over five days in an outpatient setting. The goal is to see how well patients tolerate these infusions and their effect on CRPS pain.

Participant Groups

Group I: Ketamine and Midazolam Experimental Treatment 2 Interventions

Participants will receive intravenous infusions of ketamine and midazolam for 4 hours each day, over 5 consecutive days, in an outpatient setting.

Group II: Midazolam and Saline Placebo Group 2 Interventions

Participants will receive intravenous infusions of midazolam and normal saline for 4 hours each day, over 5 consecutive days, in an outpatient setting.

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Findings from Research

A randomized double-blind placebo-controlled trial involving subjects with complex regional pain syndrome (CRPS) demonstrated that intravenous ketamine significantly reduced pain levels over a 3-month follow-up period, indicating its efficacy as a treatment option.

In contrast, the placebo group showed no significant changes in pain parameters, highlighting the effectiveness of ketamine compared to a non-active treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outpatient intravenous ketamine for the treatment of complex regional pain syndrome: a double-blind placebo controlled study. Schwartzman, RJ., Alexander, GM., Grothusen, JR., et al.[2022]

References

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

Complete recovery from intractable complex regional pain syndrome, CRPS-type I, following anesthetic ketamine and midazolam. [2013]

2. England pubmed.ncbi.nlm.nih.gov

Intravenous Ketamine Infusion for Complex Regional Pain Syndrome: Survey, Consensus, and a Reference Protocol. [2020]

3. England pubmed.ncbi.nlm.nih.gov

The use of ketamine in complex regional pain syndrome: possible mechanisms. [2013]

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

Optimizing the Treatment of CRPS With Ketamine. [2021]

5. England pubmed.ncbi.nlm.nih.gov

A possible case of complex regional pain syndrome in the orofacial region. [2013]

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

Enantioselective pharmacokinetics of (R)- and (S)-ketamine after a 5-day infusion in patients with complex regional pain syndrome. [2021]

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

Outpatient intravenous ketamine for the treatment of complex regional pain syndrome: a double-blind placebo controlled study. [2022]

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

Pharmacodynamic profiles of ketamine (R)- and (S)- with 5-day inpatient infusion for the treatment of complex regional pain syndrome. [2021]