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

Trial Summary

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 data supports the effectiveness of the drug ketamine combined with magnesium sulfate for nerve pain and PTSD?

Research shows that ketamine, often used for chronic pain, can provide pain relief and emotional benefits, especially when combined with magnesium. Studies have found that this combination can reduce pain and the need for other pain medications after surgeries, suggesting it may help with nerve pain. ^{1 2 3 4 5}

Is ketamine safe for use in humans?

Ketamine, when used at sub-anesthetic doses for pain management, has an improved safety profile compared to its use as an anesthetic. It is generally well-tolerated, though it has a history of undesirable side effects when used in higher doses. Magnesium sulfate, when used in certain doses for neuropathic pain, is also considered safe and well-tolerated, with mild side effects like a feeling of warmth. ^{1 6 7 8 9}

How does the drug combination of ketamine and magnesium sulfate differ from other treatments for nerve pain and PTSD?

The combination of ketamine and magnesium sulfate is unique because it targets the NMDA receptor, which is involved in nerve pain, through different mechanisms. This combination may provide an additive effect, potentially offering more effective pain relief than ketamine alone, especially in cases where traditional treatments are not effective. ^{1 2 3 8 10}

What is the purpose of this trial?

This study is aimed to evaluate outpatient ketamine infusion within a military chronic neuropathic pain population and its effect on PTSD. Currently, this is a pilot study with 30 participants. Participants will be randomized to (1) a moderate dose ketamine, (2) moderate dose ketamine +Mg, or (3) a magnesium control group. Participants will complete self-reported pain and PTSD questionnaires throughout the \~24-week study period. The outlined strategy will provide evidence for the utility of ketamine in neuropathic pain management and pain associated comorbidities within a military population.

Eligibility Criteria

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 either a biological male or female.

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.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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 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 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]

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]

References

1. India pubmed.ncbi.nlm.nih.gov

Ketamine versus Ketamine / magnesium Sulfate for Procedural Sedation and Analgesia in the Emergency Department: A Randomized Clinical Trial. [2022]

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

Ketamine and Magnesium for Refractory Neuropathic Pain: A Randomized, Double-blind, Crossover Trial. [2020]

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

Effect of ketamine combined with magnesium sulfate in neuropathic pain patients (KETAPAIN): study protocol for a randomized controlled trial. [2018]

4. Germany pubmed.ncbi.nlm.nih.gov

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

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

Ketamine and magnesium association reduces morphine consumption after scoliosis surgery: prospective randomised double-blind study. [2018]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Ketamine Use for Cancer and Chronic Pain Management. [2021]

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

Efficacy and safety of perioperative ketamine for the prevention of chronic postsurgical pain: A meta-analysis. [2023]

8. United States 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. [2019]

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

Synergistic interaction between ketamine and magnesium in lowering body temperature in rats. [2014]

10. Poland pubmed.ncbi.nlm.nih.gov

Additive and antagonistic antinociceptive interactions between magnesium sulfate and ketamine in the rat formalin test. [2019]