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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness and safety of combining ketamine and midazolam infusions compared to midazolam alone for treating complex regional pain syndrome (CRPS). CRPS causes severe, persistent pain, often following an injury. Participants will receive infusions over five days to determine if these treatments can reduce pain. Individuals who have experienced CRPS-related pain for three months or more and can manage daily tasks like transportation may be suitable for this study. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research has shown that ketamine infusions can reduce pain in people with complex regional pain syndrome (CRPS). Some studies indicate that about 85% of patients experience pain relief after starting ketamine treatment. Most side effects are mild and manageable.

One study found ketamine to be safe, though some patients experienced side effects like changes in perception or mood, which were generally acceptable to those treated.

Midazolam, often used to reduce anxiety, is known to be safe. When combined with ketamine, it enhances comfort during treatment.

In summary, both ketamine and midazolam are generally safe, with side effects that most patients can manage. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for complex regional pain syndrome?

Researchers are excited about using ketamine for Complex Regional Pain Syndrome (CRPS) because it targets pain differently than traditional treatments like physical therapy, nerve blocks, or opioids. Ketamine works by blocking NMDA receptors in the nervous system, which can help reset pain signals and potentially provide relief when other treatments fall short. Additionally, the combination with midazolam may enhance pain relief while minimizing the side effects often associated with ketamine. This approach offers a new avenue for CRPS management, with the potential for quicker and more significant pain reduction.

What evidence suggests that this trial's treatments could be effective for complex regional pain syndrome?

Research shows that ketamine, especially when combined with midazolam, can effectively reduce pain in people with complex regional pain syndrome (CRPS). In this trial, participants will receive either ketamine and midazolam infusions or midazolam and saline infusions. Studies have found that ketamine infusions help many patients manage pain better and improve their ability to function. Specifically, one study found that a 10-day ketamine infusion significantly reduced pain, while another study showed that 5 days of ketamine treatment provided noticeable pain relief. Using midazolam with ketamine has proven safe and without serious side effects. Although the pain relief might not last indefinitely, these treatments have given many people long-lasting improvements. ^{1 3 4 6 7}

Who Is on the Research Team?

Theresa R Lii, MD, MS

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05945147

Ketamine and Midazolam Infusions for CRPS: Feasibility ... Multi-day ketamine infusions have produced long-lasting, but not permanent, remission of symptoms in complex regional pain syndrome (CRPS), a chronic and often ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8601938/

Use of Ketamine Infusions for Treatment of Complex Regional ... Overall, a majority of the 14 studies produced positive results for the effect of ketamine infusions on improved pain control and function for ...

3. withpower.com withpower.com/trial/phase-2-complex-regional-pain-syndromes-7-2023-11cb8

Ketamine + Midazolam for Complex Regional Pain ... Research indicates that ketamine, when used with midazolam, has not led to serious complications in treating complex regional pain syndrome, thanks to careful ...

4. aetna.com aetna.com/cpb/medical/data/400_499/0447.html

Complex Regional Pain Syndrome (CRPS) / Reflex ... The authors concluded that a 4-hr ketamine infusion escalated from 40 to 80 mg over a 10-day period can result in a significant reduction of pain with increased ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0887617707001230

The neurocognitive effects of 5 day anesthetic ketamine for ... Our results revealed that 5 days of anesthetic ketamine infusion therapy is an effective treatment for CRPS I as indicated by significant reductions in both ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10688501/

Ketamine for Complex Regional Pain Syndrome: A Narrative ... Meaningful pain relief lasting 1 to 3 months can be expected in 20% to 65% of patients with complex regional pain syndrome after a single ketamine infusion, if ...

7. journals.lww.com journals.lww.com/clinicalpain/fulltext/2020/07000/optimizing_the_treatment_of_crps_with_ketamine.3.aspx

Optimizing the Treatment of CRPS With Ketamine This study aimed to develop a method that objectively measures the clinical benefits of ketamine infusions to treat complex regional pain syndrome (CRPS).