Oral Ketamine for Anxiety in Pancreatic Cancer Patients
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase < 1
Recruiting
Sponsor: Cedars-Sinai Medical Center
Must be taking: Antidepressants
Must not be taking: MAOIs
Disqualifiers: Schizophrenia, Bipolar, Severe cardiac, others
No Placebo Group
Trial Summary
What is the purpose of this trial?This is a prospective, single center, double blind, randomized, crossover feasibility study of oral ketamine versus placebo for the treatment of anxiety in patients with pancreatic cancer currently receiving or within 12 weeks of receiving cancer targeted therapy. The primary objective is to determine the feasibility of enrolling subjects and treatment adherence. The secondary objectives are to describe the safety and tolerability. Exploratory objectives are to assess the effect of ketamine/placebo on Depression, Anxiety, Physical Function, Pain Interference, Pain Intensity, Fatigue, Sleep Disturbance, and Ability to Participate in Social Roles and Activities as measured by PROMIS Anxiety Short Form 7a and the PROMIS-29 Profile v2.1 of Patient Reported Outcomes, as well as changes in circulatory inflammatory cytokines, blood glutamine levels, and other biomarkers of anxiety and/or depression.
Will I have to stop taking my current medications?
The trial allows participants to continue using standard antidepressants for anxiety if the dose has been stable for at least 12 weeks before joining the study. However, you cannot have taken a monoamine oxidase inhibitor (MAOI) within 14 days of starting the trial.
What data supports the effectiveness of the drug ketamine for anxiety in pancreatic cancer patients?
Research shows that ketamine can rapidly reduce depression and anxiety symptoms in hospice patients, suggesting it might help pancreatic cancer patients with anxiety. Additionally, ketamine has been effective in managing depression and pain in cervical cancer patients, indicating potential benefits for similar symptoms in pancreatic cancer.
12345Is oral ketamine safe for humans?
Oral ketamine has been used safely in studies for treating depression and anxiety, with doses ranging from 0.25 to 7 mg/kg. It was well tolerated in these studies, with similar dropout rates to control groups, suggesting it is generally safe for human use.
678910How is oral ketamine unique for treating anxiety in pancreatic cancer patients?
Oral ketamine is unique because it offers a rapid-acting option for anxiety relief, unlike standard treatments that may take weeks to show effects. It can be administered at home, making it more practical and accessible for patients compared to intravenous options.
1381011Eligibility Criteria
Adults with pancreatic cancer and moderate to severe anxiety, currently or recently treated for cancer, can join. They must understand English, agree to use contraception if needed, avoid alcohol and driving post-medication. Those on stable antidepressants may qualify but not if they have certain psychiatric conditions, high suicide risk, ketamine allergy, severe heart issues or uncontrolled blood pressure.Inclusion Criteria
Agrees to abstain from alcohol use while taking study medication
My liver is functioning well, as confirmed by recent tests.
Ability to understand and the willingness to sign a written informed consent
+14 more
Exclusion Criteria
My blood pressure has been over 180/100 twice in the last two months.
Refusal/inability to comply with inclusion criterion #10 (driving restrictions) and inclusion criterion #11 (alcohol abstinence) during study treatment period
I haven't taken MAOI drugs in the last 14 days.
+11 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive weekly oral administration of 0.5mg/kg ketamine or placebo for 4 weeks, followed by a crossover to the alternate treatment for another 4 weeks, separated by a 2-week washout period
10 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
This study tests oral ketamine against a placebo in reducing anxiety among pancreatic cancer patients. It's a double-blind trial where neither the participants nor the researchers know who gets what treatment until after the results are collected. The effects on mood, physical function and inflammation markers will be measured.
2Treatment groups
Experimental Treatment
Group I: Arm B: Placebo Followed by KetamineExperimental Treatment2 Interventions
Weekly oral administration of placebo for 4 weeks, followed by weekly oral administration of 0.5mg/kg ketamine for 4 weeks (separated by a washout period of 2 weeks).
Group II: Arm A: Ketamine Followed by PlaceboExperimental Treatment2 Interventions
Weekly oral administration of 0.5mg/kg ketamine for 4 weeks, followed by weekly oral administration of placebo for 4 weeks (separated by a washout period of 2 weeks).
Ketamine is already approved in United States, European Union, United States, European Union, Canada for the following indications:
🇺🇸 Approved in United States as Ketalar for:
- Anesthesia
- Treatment-resistant depression
🇪🇺 Approved in European Union as Ketalar for:
- Anesthesia
- Treatment-resistant depression
🇺🇸 Approved in United States as Spravato for:
- Treatment-resistant depression
🇪🇺 Approved in European Union as Spravato for:
- Treatment-resistant depression
🇨🇦 Approved in Canada as Spravato for:
- Treatment-resistant depression
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Cedars-Sinai Medical CenterLos Angeles, CA
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Who Is Running the Clinical Trial?
Cedars-Sinai Medical CenterLead Sponsor
References
Single Subcutaneous Ketamine Dose Followed by Oral Ketamine for Depression Symptoms in Hospice Patients: A Case Series. [2021]Management of depression symptoms in hospice patients is complicated by the fact that an appropriate trial of antidepressant therapy requires 4-6 weeks and most hospice patients receive hospice services for less than 8 weeks. Intravenously administered ketamine has been shown to produce rapid improvement in depression symptoms but is not an ideal route for hospice patients and oral ketamine appears to have a slower onset of antidepressant activity. We present a case series that illustrates the use of a single subcutaneous dose of ketamine (0.5 mg/kg) followed by daily oral ketamine (0.5 mg/kg daily) therapy to manage depression symptoms in three hospice patients. Clinical improvement of depression symptoms occurred quickly for all patients as measured by the PHQ-4, numeric ratings, and subjective reporting. A single subcutaneous dose of ketamine followed by oral therapy presents itself as an option to quickly reduce depression symptoms in hospice patients that do not also require additional pain management. Combining the use of the subcutaneous and oral routes takes advantage of the possibly faster onset, home administration, and milder side effects than intravenous dosing. Prospective studies are needed to determine which dosing strategy would be the most beneficial for hospice patients.
Implementing practice change in chronic cancer pain management: clinician response to a phase III study of ketamine. [2015]An adequately powered, double-blind, multisite, randomised controlled trial has shown no net clinical benefit for subcutaneous ketamine over placebo in the management of cancer pain refractory to combination opioid and co-analgesic therapy. The results of the trial were disseminated widely both nationally and internationally.
Daily oral ketamine for the treatment of depression and anxiety in patients receiving hospice care: a 28-day open-label proof-of-concept trial. [2023]Depression and anxiety are prevalent and undertreated in patients receiving hospice care. Standard antidepressants do not work rapidly or often enough to benefit most of these patients. Ketamine has many properties that make it an interesting candidate for rapidly treating depression and anxiety in patients receiving hospice care. To test this hypothesis, a 28-day, open-label, proof-of-concept trial of daily oral ketamine administration was conducted in order to evaluate the tolerability, potential efficacy, and time to potential efficacy in treating depression and anxiety in patients receiving hospice care.
Use of Various Doses of S-Ketamine in Treatment of Depression and Pain in Cervical Carcinoma Patients with Mild/Moderate Depression After Laparoscopic Total Hysterectomy. [2021]BACKGROUND This study investigated the effects of various doses of S-ketamine on depression and pain management of cervical carcinoma patients with mild/moderate depression. MATERIAL AND METHODS This randomized, double-blind, controlled study included 417 cervical carcinoma patients who received laparoscopic modified radical hysterectomy from April 2015 to July 2018 and who also had mild/moderate depression symptoms based on HAMD-17 scores (8~24). All patients were randomized into 4 groups: 1) the control group, 2) the racemic ketamine group, 3) the high-dose S-ketamine group; and 4) the low-dose S-ketamine group. Pain was assessed using the Visual Analogue Score (VAS), and depression was assessed using theHAMD-17 score. Serum levels of BDNF and 5-HT were measured. RESULTS The 4 groups of patients showed no significant differences in operation time, bleeding volume, hospitalization duration, or complications. The high-dose S-ketamine group showed significantly lower VAS and HAMD-17 scores than all other groups at 1 day and 3 days postoperatively, but no differences were observed in the low-dose S-ketamine group and the racemic ketamine group. The high-dose S-ketamine group showed significantly higher serum BDNF and 5-HT levels at 1 day and 3 days after surgery. However, 1 week after surgery, no difference was observed in any of the treatment groups. CONCLUSIONS At subanesthetic dose, both 0.5 mg/kg and 0.25 mg/kg S-ketamine improved short-term depression and pain for cervical carcinoma patients after surgery, and the effects were better than with the same dose of racemic ketamine.
Effects of Ketamine, S-Ketamine and MK 801 on Integrin Beta-3-mediated Cell Migration in Pancreatic Carcinoma. [2023]Label="Introduction" NlmCategory="UNASSIGNED">Pancreatic ductal adenocarcinoma is one of the most aggressive malignancies in humans. The main reason for its unfavourable prognosis is the combination of rapid tumour growth, early-onset metastasis and currently still inadequate diagnostic and therapeutic options. Thus, only very few patients are eligible for radical resection of the primary tumour as the only curative treatment option available so far. In the perioperative period, tumour progression and metastasis are facilitated by the activation of key signalling pathways and the altered regulation of transcription factors. Various tumour entities have shown increased expression of the integrin-3 receptor subunit, which correlates with more rapid tumour progression and metastasis through advanced migration, invasion and proliferation. The influence of perioperative medication and postoperative pain management remains unclear. To investigate the effects of ketamine, s-ketamine and MK 801 on integrin beta-3-mediated cell migration in pancreatic cancer cells in vitro.
Pharmacokinetics and Safety of Esketamine in Chinese Patients Undergoing Painless Gastroscopy in Comparison with Ketamine: A Randomized, Open-Label Clinical Study. [2022]To assess the pharmacokinetics and safety of pure S-ketamine (esketamine) in Chinese patients undergoing painless gastroscopy and evaluate the potential advantage of esketamine in clinical treatment compared with racemate ketamine hydrochloride injection.
Oral Ketamine for Depression, 2: Practical Considerations. [2020]The oral route of administration is probably the least expensive and most convenient way to administer ketamine in indicated contexts in depressed patients. Because only 20%-25% of orally administered ketamine reaches systemic circulation, oral doses of about 2.0-2.5 mg/kg may need to be administered to achieve equivalence to intravenously administered ketamine. In case reports, case series, standard operating practice in ketamine facilities, and randomized controlled trials, oral ketamine has been administered through weight-based dosing and as fixed doses, and the dosing strategy has been one-size-fits-all or individualized through a dose discovery process. Administered doses have ranged from 0.25 to 7.0 mg/kg in weight-based dosing sessions and from 25 mg to 300 mg in fixed dosing sessions. This article reviews strategies for dosing with oral ketamine, dose discovery procedures, rates of dosing during a session, the frequency of dosing sessions and the duration of treatment, treatment in the clinic vs domiciliary treatment, adverse effects and risks, and safety issues. Finally, this article provides a detailed account of practices and experiences with oral ketamine so that readers may know what to expect when the treatment is orally administered. Whereas oral ketamine appears to be a safe and effective treatment and could make ketamine an accessible and affordable intervention in less privileged medical facilities, readers are warned that the literature on oral ketamine is thin and that there are many areas that need more investigation, especially matters related to pharmacokinetics, physiologic effects, abuse potential and strategies to mitigate illicit use, and adverse effects and efficacy relative to other routes of administration. Until studies of a sufficiently high quality become available, the use of oral ketamine to treat depression must be considered experimental.
Oral Ketamine for Depression, 1: Pharmacologic Considerations and Clinical Evidence. [2019]Clinical evidence is accumulating to support the use of ketamine as a powerful, quick-acting intervention for depression. Ketamine has been administered by oral, sublingual, transmucosal, intravenous, intramuscular, subcutaneous, intranasal, and even rectal routes. Whereas intravenous ketamine is the best studied approach, common sense dictates that oral ketamine is the most practical. The bioavailability of oral ketamine and interindividual variations thereof have been poorly studied; possibly only 20%-25% of an oral dose reaches the bloodstream. This is not necessarily a limitation because, as with other drugs that have poor oral bioavailability, compensation is possible by administering an appropriately higher dose, and interindividual variations can be addressed through individualized dose up-titration. A quarter- century of experience supports the use of oral ketamine for treating acute and chronic pain in children and adults. Case reports, case series, chart reviews, and 3 recent randomized controlled trials (RCTs) show that oral ketamine is effective in treating severe depression, depression with suicidal ideation, and treatment-resistant depression; that oral ketamine, used as an augmentation agent, improves outcomes in patients receiving a conventional antidepressant; and that oral ketamine reduces depression in patients with chronic pain. Doses of oral ketamine have ranged from 0.25 to 7 mg/kg and from 50 mg per occasion to 300 mg per occasion in multiple daily dosing, daily dosing, and intermittent dosing schedules. Oral ketamine was well tolerated in all studies; dropout and reasons for dropout were similar in ketamine and control arms in the 3 RCTs. These findings suggest that if ketamine is to find a place as an off-label treatment for depression and suicidality in mainstream psychiatry, researchers should study the safety, efficacy, and optimization of oral ketamine. Intravenous and intranasal routes may be monetarily more promising, but the oral route could be of greatest service.
The effectiveness of ketamine on anxiety, irritability, and agitation: Implications for treating mixed features in adults with major depressive or bipolar disorder. [2021]To determine the effectiveness of intravenous (IV) ketamine on anxiety, irritability, agitation, and suicidality, in adults with treatment-resistant major depressive disorder (MDD) or bipolar disorder (BD).
Oral ketamine for the rapid treatment of depression and anxiety in patients receiving hospice care. [2021]Depression is prevalent and undertreated in patients receiving hospice care. Standard antidepressants do not work rapidly or often enough to benefit most of these patients. Here, two cases are reported in which a single oral dose of ketamine provided rapid and moderately sustained symptom relief for both depression and anxiety. In addition, no adverse effects were noted. Further investigation with randomized, controlled clinical trials is necessary to firmly establish the effectiveness of oral ketamine for the treatment of depression and anxiety in patients receiving hospice care. Ketamine may be a promising safe, effective, and cost-effective rapid treatment for depression and anxiety in this population.
Compounded oral ketamine. [2013]The nonnarcotic nonaddictive neuropathic pain reliever ketamine, which was synthesized in the early 1960s by Parke-Davis, was first administered to human patients in 1965. Used by the U. S. military as a field anesthetic during the Vietnam War, it slowly became popular as both an induction and maintenance agent for the general anesthesia required during brief surgical procedures. The use of ketamine in the past has been limited primarily to intravenous administration in hospitalized patients. Very recently, several published reports have described the use of low-dose ketamine for the relief of pain, refractory depression, and anxiety in patients with or without cancer. Because chronic pain, depression, and anxiety often occur in hospice patients with or without cancer and in palliative care patients who are not eligible for hospice, the discovery of new and effective uses for an established drug to treat those conditions has excited interest in the palliative care community. We support that interest with this case report, which describes our experience in treating a 44-year-old male hospice patient with severe constant anxiety, fear, and depression in addition to multiple near-terminal comorbid physical conditions that produce chronic pain. Prior treatments prescribed to resolve this patient's pain, anxiety, and depression had proven ineffective. However, a single low-dose (0.5 mg/kg) subcutaneous test injection of ketamine provided dramatic relief from those symptoms for 80 hours, although the anesthetic effects of that drug are not of long duration. This good outcome has been sustained to date by daily treatment with a compounded flavored oral ketamine solution (40 mg/5 mL) that is not commercially available. Flavoring the solution masks the bitter taste of ketamine and renders the treatment palatable. We found ketamine to be a well-tolerated and effective treatment for the triad of severe anxiety, chronic pain, and severe depression in a hospice patient with multiple comorbid conditions. To our knowledge, this report chronicles the first use of compounded oral ketamine for home-based palliative or hospice care in Louisiana. A formulation for a flavored oral ketamine solution is provided for easy reference.