What side effects are associated with this type of intervention?

Common treatments for Complex Regional Pain Syndrome (CRPS) include ketamine (an NMDA receptor antagonist) and midazolam (a GABA receptor agonist). Ketamine can cause side effects such as hallucinations, confusion, increased blood pressure, and nausea. Midazolam, on the other hand, may lead to drowsiness, dizziness, respiratory depression, and dependency with long-term use. Other treatments for CRPS, such as anticonvulsants and opioids, also have side effects including sedation, gastrointestinal issues, and potential for abuse. It is important to discuss these potential side effects with a healthcare provider to determine the best treatment plan.

What prior FDA approvals exist?

The FDA has not specifically approved any drugs solely for the treatment of Complex Regional Pain Syndrome (CRPS). However, treatments often involve medications that target neuropathic pain, such as gabapentinoids (e.g., gabapentin, pregabalin), which act on GABA receptors, and NMDA receptor antagonists like ketamine. Ketamine, in particular, has been studied for its efficacy in treating CRPS due to its NMDA receptor antagonism, which helps in reducing pain by modulating central sensitization. Midazolam, a GABA receptor agonist, is not specifically approved for CRPS but is used for its sedative and anxiolytic properties, which can be beneficial in managing the overall pain experience in CRPS patients.

What other types of research exist?

Promising alternatives to Ketamine plus Midazolam for CRPS include: 1) Gabapentin and Pregabalin, which are effective for neuropathic pain; 2) Cannabinoids, such as Nabiximols, which have shown efficacy in chronic pain management; 3) Topical Capsaicin, which can provide relief for neuropathic pain; 4) Botulinum Toxin Type A, which has been used for neuropathic pain in spinal cord injury patients. These alternatives have demonstrated potential in clinical studies and may offer effective pain management for CRPS patients.

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Ketamine + Midazolam for Complex Regional Pain Syndrome

Phase 2

Waitlist Available

Led By Theresa R Lii, MD, MS

Research Sponsored by Stanford University

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Meets IASP diagnostic criteria for CRPS

Age 18 to 65 years

Timeline

Screening 3 weeks

Treatment Varies

Follow Up weekly for 8 weeks after the end of treatment

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Ketamine may cause changes in blood pressure, dizziness, nausea, perceptual disturbances (like hallucinations), and mood changes. Midazolam can lead to sleepiness, memory issues, and sometimes paradoxical reactions like anxiety or agitation.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have been diagnosed with Complex Regional Pain Syndrome.

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I am between 18 and 65 years old.

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

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

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline, and weekly for 8 weeks after the end of treatment

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline, and weekly for 8 weeks after the end of treatment

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline, and weekly for 8 weeks after the end of treatment for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Change in investigator masking

Change in participant masking

Number and proportion of patients who can undergo the steps of recruitment, informed consent, enrollment, and randomization

+2 more

Secondary study objectives

Anxiety

Chronic pain acceptance

Depression (PHQ-9)

+9 more

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: Ketamine and MidazolamExperimental Treatment2 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 SalinePlacebo Group2 Interventions

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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Ketamine

2011

Completed Phase 4

~1120

Midazolam

2018

Completed Phase 4

~1910

0 / 4Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Ketamine, an NMDA receptor antagonist, blocks NMDA receptors in the brain and spinal cord, reducing central sensitization and pain transmission in CRPS. Midazolam, a GABA receptor agonist, enhances GABA's inhibitory effects, reducing anxiety and muscle spasms. These mechanisms are important for CRPS patients as they target both excitatory and inhibitory pathways, helping to manage pain and improve quality of life.