Ketamine for Nerve Pain and PTSD
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Recruiting
Sponsor: Margaux M. Salas, PhD
Must not be taking: Theophylline, Benzodiazepines
Disqualifiers: Psychosis, TBI, Hypertension, others
No Placebo Group
Prior Safety Data
Trial Summary
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.
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.
12345Is 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.
16789How 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.
123810Eligibility 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 between 18 and 70 years old and have had chronic nerve pain for at least 3 months.
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.
+3 more
Trial 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
Participant Groups
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.
3Treatment groups
Experimental Treatment
Active Control
Group I: Moderate dose ketamine + magnesium sulfateExperimental Treatment1 Intervention
0.50 mg/kg/hr ketamine + 750 mg/hr Mg
Group II: Moderate Dose KetamineExperimental Treatment1 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 sulfateActive Control1 Intervention
750 mg/hr
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Brooke Army Medical CenterSan Antonio, TX
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Who Is Running the Clinical Trial?
Margaux M. Salas, PhDLead Sponsor
References
Ketamine versus Ketamine / magnesium Sulfate for Procedural Sedation and Analgesia in the Emergency Department: A Randomized Clinical Trial. [2022]Label="BACKGROUND" NlmCategory="BACKGROUND">The present study was designed to evaluate the effectiveness of magnesium sulfate (MgSO4) in procedural sedation and analgesia (PSA) when combined with ketamine in patients with fractures in emergency departments and required short and painful emergency procedures.
Ketamine and Magnesium for Refractory Neuropathic Pain: A Randomized, Double-blind, Crossover Trial. [2020]Ketamine is often used for the management of refractory chronic pain. There is, however, a paucity of trials exploring its analgesic effect several weeks after intravenous administration or in association with magnesium. The authors hypothesized that ketamine in neuropathic pain may provide pain relief and cognitive-emotional benefit versus placebo and that a combination with magnesium may have an additive effect for 5 weeks.
Effect of ketamine combined with magnesium sulfate in neuropathic pain patients (KETAPAIN): study protocol for a randomized controlled trial. [2018]Neuropathic pain is difficult to treat, and the efficacy of recommended drugs remains limited. N-methyl-D-aspartate receptors are implicated, and antagonists are a pharmacological option. Ketamine is widely used in French pain clinics, but without consensus or recommendations. Furthermore, the association of ketamine with magnesium has been poorly studied. The aim of the present study is to evaluate the benefit of ketamine with or without magnesium in refractory neuropathic pain.
[Ketamine for treatment of chronic pain: meta-analysis]. [2019]The idea of using Ketamine to treat chronic pain is mainly based on the central antinoceptive effect of the substance acting as a noncompetitive antagonist at the NMDA-receptor. In the present meta analysis over a period from 1/1981 up to 6/1996 twelve publications (1994-1996), which have dealt the use of Ketamine for patients with chronic pain, are evaluated and discussed. The entire positive evaluation of the drug is based on the results of the studies under consideration. The studies investigating 88 cases are classified, i.e. seven studies are assigned to level 3, two studies to level 4, and three studies to level 5. A significant reduction of pain has been proven for patients with neuropathic pain by four cross-over-studies comparing the drug with placebo. However, observations have been restricted to a few hours after the administration of the drug. A positive effect of Ketamine as compared with opioids has been demonstrated by three studies, one of them with statistical significance. Positive long term results have been observed by two studies considering the subcutaneous and intravenous application of Ketamine (72-480 mg, daily) to 14 cancer pain patients, to whom opioids have been administered with insufficient effects before. A successful five-week-application (oral) of Ketamine has been described convincingly in a case report of a patient with postherpetic neuralgia. Two studies interpret the additional intrathecal administration of Ketamine to cancer patients as a possibility of either impeding the development of tolerance of the local anesthetic or reducing morphine requirements. Only one paper has dealt with the known side effects of Ketamine. Here, the therapy had to break off in two cases. In nine cases the side effects could be suppressed by Droperidol. For the future, research with more study power is necessary to establish Ketamine in the therapy of chronic pain.
Ketamine and magnesium association reduces morphine consumption after scoliosis surgery: prospective randomised double-blind study. [2018]Scoliosis repair is a major orthopaedic surgery associated with severe post-operative pain. Ketamine and magnesium have an established efficacy as morphine-sparing agents. Our purpose was to evaluate the morphine-sparing effect of both magnesium and ketamine given simultaneously compared with ketamine alone during scoliosis surgery.
Ketamine Use for Cancer and Chronic Pain Management. [2021]Ketamine, an N-methyl-D-aspartate receptor antagonist, is widely known as a dissociative anesthetic and phencyclidine derivative. Due to an undesirable adverse event profile when used as an anesthetic it had widely fallen out of human use in favor of more modern agents. However, it has recently been explored for several other indications such as treatment resistant depression and chronic pain. Several recent studies and case reports compiled here show that ketamine is an effective analgesic in chronic pain conditions including cancer-related neuropathic pain. Of special interest is ketamine's opioid sparing ability by counteracting the central nervous system sensitization seen in opioid induced hyperalgesia. Furthermore, at the sub-anesthetic concentrations used for analgesia ketamine's safety and adverse event profiles are much improved. In this article, we review both the basic science and clinical evidence regarding ketamine's utility in chronic pain conditions as well as potential adverse events.
Efficacy and safety of perioperative ketamine for the prevention of chronic postsurgical pain: A meta-analysis. [2023]Assessment of the efficacy and safety of perioperative intravenous ketamine in reducing incidence and severity of chronic postsurgical pain.
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]Neuropathic pain may respond poorly to morphine and is often difficult to relieve. Recent attention has been drawn to the role of the N-methyl-D-aspartate (NMDA) receptor in the potentiation of neuropathic pain. Magnesium is known to block the NMDA receptor. It reduces the neuropathic pain response in animals, and attenuates postoperative pain and migraine in humans. We have examined the safety, tolerability, and efficacy of two intravenous doses of magnesium sulfate in 12 patients with neuropathic pain due to malignant infiltration of the brachial or lumbosacral plexus. The first six patients received 500 mg, the remainder 1 g. Apart from a mild feeling of warmth at the time of the injection, both doses were well tolerated. After receiving 500 mg, three patients experienced complete pain relief and two experienced partial pain relief for up to 4 hours duration; pain was unchanged in one patient. After receiving 1 g, one patient experienced complete relief and four experienced partial pain relief of similar duration; pain was unchanged in one patient. Intravenous magnesium sulfate in these doses appears to be safe and well tolerated. A useful analgesic effect may be obtained in some patients and further evaluation is warranted.
Synergistic interaction between ketamine and magnesium in lowering body temperature in rats. [2014]A large body of evidence supports the existence of an endogenous glutamate system that tonically modulates body temperature via N-methyl-d-aspartate (NMDA) receptors. Ketamine and magnesium, both NMDA receptor antagonists, are known for their anesthetic, analgesic and anti-shivering properties. This study is aimed at evaluating the effects of ketamine and magnesium sulfate on body temperature in rats, and to determine the type of interaction between them. The body temperature was measured by insertion of a thermometer probe 5cm into the colon of unrestrained male Wistar rats (200-250g). Magnesium sulfate (5 and 60mg/kg, sc) showed influence neither on baseline, nor on morphine-evoked hyperthermic response. Subanesthetic doses of ketamine (5-30mg/kg, ip) given alone, produced significant dose-dependent reduction in both baseline colonic temperature and morphine-induced hyperthermia. Analysis of the log dose-response curves for the effects of ketamine and ketamine-magnesium sulfate combination on the baseline body temperature revealed synergistic interaction, and about 5.3 fold reduction in dosage of ketamine when the drugs were applied in fixed ratio (1:1) combinations. In addition, fixed low dose of magnesium sulfate (5mg/kg, sc) enhanced the temperature lowering effect of ketamine (1.25-10mg/kg, ip) on baseline body temperature and morphine-induced hyperthermia by factors of about 2.5 and 5.3, respectively. This study is the first to demonstrate the synergistic interaction between magnesium sulfate and ketamine in a whole animal study and its statistical confirmation. It is possible that the synergy between ketamine and magnesium may have clinical relevance.
Additive and antagonistic antinociceptive interactions between magnesium sulfate and ketamine in the rat formalin test. [2019]Because ketamine and magnesium block NMDA receptor activation by distinct mechanisms of action, we hypothesized that in a model of inflammatory pain in rats the combination of ketamine and magnesium might be more effective than ketamine alone. Antinociceptive activity was assessed by the formalin test in male Wistar rats (200-250 g). Animals were injected with 100 μL of 2.5% formalin to the plantar surface of the right hind paw. Data were recorded as the total time spent in pain-related behavior after the injection of formalin or vehicle (0.9% NaCl). Ketamine and magnesium sulfate given separately reduced nocifensive behavior in the second phase of the formalin test in rats. When ketamine was applied after magnesium sulfate, the log dose-response curves for the effects of ketamine and the magnesium sulfate-ketamine combination revealed antagonistic interaction, and about 1.6 (CL 1.2-2.4) fold increment in ketamine dosage. A low dose of magnesium sulfate (5 mg/kg, subcutaneously) administered after ketamine increased the antinociceptive effect of ketamine by a factor of only 1.2 (CL 0.95-1.38), indicating an additive interaction. There was a 1.8-fold reduction in dosage of ketamine when ketamine was administered before rather than after the magnesium sulfate. The present study revealed that both ketamine and magnesium reduced pain-related behavior in the second phase of the formalin test in rats. Ketamine, when administered before or after the magnesium, provided additive or antagonistic antinociceptive interactions, respectively. Whether there will be an additive or antagonistic antinociceptive interaction between ketamine and magnesium depends on the order of drug administration.