Ketamine for Nerve Pain and PTSD

Overseen By Margaux M Salas, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Margaux M. Salas, PhD

Must not be taking: Theophylline, Benzodiazepines

Disqualifiers: Psychosis, TBI, Hypertension, 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: 5

Duration: 24 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how ketamine, a medication used for pain relief and mood disorders, can assist individuals with nerve pain and PTSD (post-traumatic stress disorder). The study evaluates the effectiveness of different combinations of ketamine and magnesium (a mineral supplement) in reducing pain and PTSD symptoms. It specifically seeks active duty military, veterans, or retirees who have experienced chronic nerve pain for at least three months and have moderate pain levels. Participants will provide feedback on their pain and PTSD symptoms over approximately 24 weeks. As a Phase 4 trial, this study involves an FDA-approved treatment and aims to understand how ketamine benefits more patients.

Will I have to stop taking my current medications?

The trial requires participants to stop using certain medications, including Theophylline, Aminophylline, Sympathomimetics, Vasopressin, and Benzodiazepines. If you are taking any of these, you will need to stop before participating.

What is the safety track record for these treatments?

Research has shown that ketamine is generally safe, with manageable side effects. One study treated 50 patients with a specific pain condition using ketamine, and side effects did not pose a major problem. However, another review noted insufficient strong evidence to confirm ketamine's safety and effectiveness for long-term pain relief.

Some studies are exploring the potential benefits of combining ketamine with magnesium sulfate for difficult-to-treat nerve pain. Researchers are carefully studying this combination to assess its safety and effectiveness. While ketamine is already used in medical settings and considered safe, more specific evidence is needed for its long-term use in treating nerve pain and PTSD. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments because ketamine offers a novel approach to treating nerve pain and PTSD compared to traditional options like opioids, antidepressants, and anticonvulsants. Ketamine works by modulating the NMDA receptors in the brain, which is a different mechanism than the typical treatments that primarily focus on neurotransmitters like serotonin and norepinephrine. The combination of ketamine with magnesium sulfate could enhance the effectiveness by providing additional NMDA receptor modulation and neuroprotective benefits. This unique approach holds promise for faster relief and potentially fewer side effects, making it a compelling alternative to current therapies.

What evidence suggests that this trial's treatments could be effective for nerve pain and PTSD?

Studies have shown that ketamine can help with both nerve pain and PTSD. Research indicates that adding ketamine to the treatment of long-term nerve pain can significantly reduce pain. One study found that 46% of patients experienced a meaningful improvement in their pain. For PTSD, ketamine is considered a promising option, especially when combined with therapy. In this trial, some participants will receive a moderate dose of ketamine alone, while others will receive a combination of moderate dose ketamine and magnesium sulfate. Some evidence suggests that combining ketamine with magnesium sulfate might offer extra benefits for those with stubborn nerve pain. Overall, both treatments show potential for helping people with nerve pain and PTSD. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for military personnel, veterans, and retirees aged 18-70 with chronic nerve pain lasting at least 3 months. Participants must not have used ketamine in the past year and should have moderate pain levels (4-7 on a scale). Women of childbearing age must use contraception and agree to pregnancy tests.

Inclusion Criteria

I am not planning to become pregnant and agree to use contraception and undergo pregnancy tests during the study.

I am currently serving, a veteran, or retired from the military.

I am either a biological male or female.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive ketamine or magnesium infusions with diminishing frequency over 6 weeks, followed by booster treatments at weeks 10 and 24

24 weeks

3 visits per week (Weeks 1-2), 2 visits per week (Weeks 3-4), 1 visit per week (Weeks 5-6), 1 visit (Week 10), 1 visit (Week 24)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Ketamine
• Magnesium sulfate

Trial Overview

The study compares three groups: one receiving a moderate dose of ketamine, another getting ketamine plus magnesium sulfate, and a control group taking only magnesium sulfate. It aims to assess the impact on neuropathic pain and PTSD over approximately six months.

How Is the Trial Designed?

Group I: Moderate dose ketamine + magnesium sulfate Experimental Treatment 1 Intervention

0.50 mg/kg/hr ketamine + 750 mg/hr Mg

Group II: Moderate Dose Ketamine Experimental Treatment 1 Intervention

0.5 mg/kg/hr The total amount of ketamine for each participant is dependent on their body weight in kg per ideal body weight (IBW) formula. This total ketamine dose will be injected into one 250 ml normal saline 0.9% solution with a rate of 62.5 ml/hr over four hours or until the contents of the bag are infused and flushed with 20 ml of normal saline

Group III: Magnesium sulfate Active Control 1 Intervention

750 mg/hr

Who Is Running the Clinical Trial?

Margaux M. Salas, PhD

Lead Sponsor

Trials

1

Recruited

30+

Published Research Related to This Trial

In a study involving 20 patients with neuropathic pain, ketamine did not significantly reduce pain intensity compared to placebo over a 35-day period, indicating it may not provide long-term pain relief in this context.

The combination of ketamine with magnesium sulfate also showed no added benefit for pain relief or cognitive-emotional improvement, and the incidence of adverse events was relatively low across all treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine and Magnesium for Refractory Neuropathic Pain: A Randomized, Double-blind, Crossover Trial. Pickering, G., Pereira, B., Morel, V., et al.[2020]

In a study of 50 patients undergoing scoliosis surgery, the combination of ketamine and magnesium significantly reduced post-operative morphine consumption by 29.5% compared to ketamine alone, indicating a strong morphine-sparing effect.

Patients receiving the ketamine and magnesium combination reported better sleep quality and higher satisfaction scores on the first night post-surgery, suggesting additional benefits beyond pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine and magnesium association reduces morphine consumption after scoliosis surgery: prospective randomised double-blind study. Jabbour, HJ., Naccache, NM., Jawish, RJ., et al.[2018]

This study will evaluate the effectiveness of ketamine, both alone and in combination with magnesium sulfate, in treating refractory neuropathic pain in 22 patients, using a randomized, double-blind, crossover design.

The primary measure of effectiveness will be the change in pain intensity over a 5-week period, assessed using a 0-10 Numeric Pain Rating Scale, which could provide insights into a potentially valuable treatment option for neuropathic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of ketamine combined with magnesium sulfate in neuropathic pain patients (KETAPAIN): study protocol for a randomized controlled trial. Delage, N., Morel, V., Picard, P., et al.[2018]

In a study involving 12 patients with neuropathic pain from malignant infiltration, intravenous magnesium sulfate was found to be safe and well tolerated, with only mild side effects reported.

The treatment showed potential analgesic effects, with some patients experiencing complete or partial pain relief lasting up to 4 hours, suggesting that magnesium sulfate could be a promising option for managing neuropathic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety and efficacy of a single dose (500 mg or 1 g) of intravenous magnesium sulfate in neuropathic pain poorly responsive to strong opioid analgesics in patients with cancer. Crosby, V., Wilcock, A., Corcoran, R.[2019]

In a rat model of inflammatory pain, both ketamine and magnesium sulfate were effective in reducing pain-related behavior, indicating their potential as pain relief options.

The interaction between ketamine and magnesium sulfate depends on the order of administration: administering ketamine before magnesium resulted in an additive effect, while administering it after led to an antagonistic effect, suggesting careful consideration is needed for their combined use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Additive and antagonistic antinociceptive interactions between magnesium sulfate and ketamine in the rat formalin test. Vujović, KS., Vučković, S., Vasović, D., et al.[2019]

A systematic review of 36 randomized controlled trials involving 3572 patients found that perioperative intravenous ketamine does not significantly reduce the incidence of chronic postsurgical pain after 6 months compared to placebo.

However, ketamine may lower the incidence of chronic postsurgical neuropathic pain after 3 months, although it also increases the risk of postoperative side effects like nystagmus and visual disturbances.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of perioperative ketamine for the prevention of chronic postsurgical pain: A meta-analysis. Abouarab, AH., Brülle, R., Aboukilila, MY., et al.[2023]

In a study involving male Wistar rats, ketamine significantly reduced body temperature in a dose-dependent manner, while magnesium sulfate did not affect baseline temperature or morphine-induced hyperthermia.

The combination of ketamine and magnesium sulfate showed a synergistic effect, allowing for a 5.3-fold reduction in the required dose of ketamine, suggesting potential clinical benefits in using these drugs together for temperature modulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synergistic interaction between ketamine and magnesium in lowering body temperature in rats. Vučković, SM., Savić Vujović, KR., Srebro, DP., et al.[2014]

A meta-analysis of 12 studies involving 88 patients indicates that Ketamine significantly reduces neuropathic pain compared to placebo, although the effects are typically short-lived after administration.

Ketamine has shown promise as an alternative to opioids for chronic pain management, with some studies reporting positive long-term outcomes, but further research with larger sample sizes is needed to confirm its efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Ketamine for treatment of chronic pain: meta-analysis]. Wiedemann, B.[2019]

Ketamine has been found to be an effective treatment for chronic pain conditions, including cancer-related neuropathic pain, and can help reduce the need for opioids by counteracting opioid-induced hyperalgesia.

At sub-anesthetic doses, ketamine demonstrates a significantly improved safety profile and fewer adverse events compared to its use as an anesthetic, making it a promising option for pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine Use for Cancer and Chronic Pain Management. Culp, C., Kim, HK., Abdi, S.[2021]

In a study of 100 patients requiring procedural sedation for fractures, the combination of magnesium sulfate (MgSO4) and ketamine did not significantly improve muscle relaxation compared to ketamine alone.

The results indicated that while MgSO4 was added to ketamine for sedation, it did not provide any additional benefit in muscle relaxation during emergency procedures, suggesting that this combination may not be effective for this purpose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine versus Ketamine / magnesium Sulfate for Procedural Sedation and Analgesia in the Emergency Department: A Randomized Clinical Trial. Azizkhani, R., Bahadori, A., Shariati, M., et al.[2022]

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