Ketamine Tablets for Complex Regional Pain Syndrome

Overseen By Yao-Ping Zhang

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Southern California

Must not be taking: Opioids, Cocaine, Amphetamines, others

Disqualifiers: Cardiovascular disease, Psychotic illness, Renal conditions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 8

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new form of ketamine tablets to determine their effectiveness in reducing pain for individuals with complex regional pain syndrome (CRPS), a condition causing chronic pain in a limb. Researchers aim to assess the tablets' efficacy, safety, and impact on participants' quality of life. The trial seeks individuals who have experienced CRPS for at least six months and have maintained stability on their current treatment plan. Participants should have significant pain in the affected limb and be willing to try a new medication routine. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

You may need to stop taking certain medications. If you are on ketamine therapy, you must stop at least 14 days before the study starts. Additionally, any prohibited medications must be stopped 14 days before the study and throughout its duration.

Is there any evidence suggesting that Ketamine HCl Prolonged Release tablets are likely to be safe for humans?

Research has shown that ketamine infusions, similar to the slow-release tablets under study, have been safe for individuals with chronic pain. Studies have found that using ketamine for pain management over time is generally well-tolerated.

Some individuals experienced side effects, usually mild and manageable, such as dizziness and nausea. It's important to note that these results come from those who received ketamine in a different form, such as infusions, not tablets.

This trial tests a slow-release tablet, which might alter how the body processes the drug. The trial is in an early stage to ensure its safety and effectiveness in this form. Although ketamine is approved for other treatments, this study will help confirm its safety specifically for complex regional pain syndrome (CRPS). ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for CRPS?

Most treatments for Complex Regional Pain Syndrome (CRPS) rely on pain management methods like physical therapy, nerve blocks, or medications such as corticosteroids and opioids. Unlike these standard options, ketamine tablets offer a unique approach by using ketamine HCl in a prolonged release oral form. This delivery method allows for continuous, controlled release of the active ingredient, potentially providing more consistent pain relief. Researchers are excited because ketamine works by blocking NMDA receptors, which play a role in pain perception, offering a novel mechanism of action that may be more effective for individuals who have not found relief with other treatments.

What evidence suggests that this treatment might be an effective treatment for complex regional pain syndrome?

Research has shown that ketamine can help treat complex regional pain syndrome (CRPS). Studies have found that ketamine infusions reduce pain in CRPS patients more effectively than in other chronic pain conditions. In one study, patients who received a high-dose infusion experienced complete pain relief lasting 5 to 11 years. While these results are encouraging, this trial will test ketamine in a tablet form that releases the medication slowly over time. Early signs suggest this could provide similar benefits in managing CRPS pain. ^{1 3 4 5 6}

Who Is on the Research Team?

Steven Richeimer, MD

Principal Investigator

Keck Medical Center of USC

Are You a Good Fit for This Trial?

This trial is for individuals experiencing pain from Complex Regional Pain Syndrome (CRPS). Specific eligibility criteria are not provided, but typically participants must meet certain health standards and may be required to have a confirmed diagnosis of CRPS.

Inclusion Criteria

For persons of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional 6 weeks after the end of study intervention administration

I agree to stop taking certain medications 14 days before the study starts and during it.

I have had CRPS for at least 6 months.

Exclusion Criteria

Abnormal EKG results, abnormal blood pressure and/or heart rates

Positive urine screen for any of the following: cocaine, amphetamine, methamphetamine, PCP, opioids, THC (other than medication used for individual standard treatment of pain) at Visit 1

Known or suspected acute or chronic alcoholism, delirium tremens, or toxic psychosis

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

3 weeks

1 visit (in-person)

Treatment

Participants receive Ketamine HCl PR tablets, starting with 40mg BID, with potential dose increase at week 4

12 weeks

6 visits (in-person), 4 visits (virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Ketamine HCl Prolonged Release Oral Tablets

Trial Overview

The study is testing the safety and how well the body handles Ketamine HCl Prolonged Release tablets at different strengths: 80mg, 160mg, and 240mg. It will also check if these doses can help manage CRPS pain effectively.

How Is the Trial Designed?

Group I: 80mg Ketamine HCl PR Experimental Treatment 2 Interventions

One 40mg tablet of Ketamine HCl PR twice a day, which may be increased to two 40mg tablets Ketamine HCl PR twice a day at week 4 if subject does not experience adequate pain relief.

Who Is Running the Clinical Trial?

University of Southern California

Lead Sponsor

Trials

956

Recruited

1,609,000+

Published Research Related to This Trial

A review of 41 treatment arms from 21 studies found that ketamine formulations that maximize first pass metabolism and delay the time to peak concentration (Tmax) are associated with better safety and tolerability, particularly in reducing side effects like dissociation and increased blood pressure.

The study revealed strong correlations between the ketamine:norketamine ratio and both dissociation ratings and blood pressure changes, suggesting that careful formulation can help minimize adverse effects while maintaining the antidepressant efficacy of ketamine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of formulation and route of administration on ketamine's safety and tolerability: systematic review. Glue, P., Russell, B., Medlicott, NJ.[2021]

An extended release oral ketamine tablet was found to be safe and well tolerated in a study of seven patients with treatment-resistant depression/anxiety, with no significant changes in vital signs and only one brief report of dissociation.

All patients experienced over 50% improvements in mood ratings over 96 hours, suggesting that while the onset of mood improvement is slightly delayed compared to injectable forms, this oral formulation could be a promising option for treating resistant depression and anxiety disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of extended release ketamine tablets in patients with treatment-resistant depression and anxiety: open label pilot study. Glue, P., Medlicott, NJ., Neehoff, S., et al.[2022]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06419985

Ketamine HCl Prolonged Release Oral Tablets for CRPS

The purpose of this study is to evaluate the efficacy of Ketamine HCl Prolonged Release (PR) tablets in participants with pain due to complex regional pain ...

2.

pmc.ncbi.nlm.nih.gov

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

Ketamine for Complex Regional Pain Syndrome: A Narrative ...

In the high-dose, open-label anesthetic infusion (3-7 mg/kg/h) study by Kiefer and colleagues, 50% of participants experienced 5 to 11 years of complete pain ...

3.

pmc.ncbi.nlm.nih.gov

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

Use of Ketamine Infusions for Treatment of Complex Regional ...

Overall, the use of ketamine resulted in the greatest pain score reductions in patients with CRPS than any other chronic pain condition.

4.

blossomanalysis.com

blossomanalysis.com/trials/ketamine-hcl-prolonged-release-oral-tablets-for-crps/

Ketamine HCl Prolonged Release Oral Tablets for CRPS

The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetic profile of Ketamine HCl Prolonged Release (PR) tablets in participants ...

5.

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 ...

6.

ctv.veeva.com

ctv.veeva.com/study/ketamine-hcl-prolonged-release-oral-tablets-for-crps

Ketamine HCl Prolonged Release Oral Tablets for CRPS

The purpose of this study is to evaluate the efficacy of Ketamine HCl Prolonged Release (PR) tablets in participants with pain due to complex regional pain ...