Ketamine + Talk Therapy for Pancreatic Cancer

Overseen By Zoe Lopez-Meraz

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Brian Anderson, MD

Must be taking: Opioids

Must not be taking: Lamotrigine, Clozapine, Anxiolytics, others

Disqualifiers: Ketamine use, Stroke, 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: 4

Duration: 28 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a single dose of ketamine (an anesthetic and pain management drug) combined with talk therapy can reduce feelings of demoralization and pain in patients with advanced gastrointestinal cancers. People with stage 3 or 4 GI cancers often experience distress and pain, sometimes managed with opioids. Ketamine has shown benefits in treating depression and pain in other contexts, so researchers aim to determine its effectiveness for these cancer patients. Those with stage 3 or 4 pancreatic, colorectal, or similar GI cancers who experience significant demoralization may be suitable for this trial. As a Phase 4 trial, this research seeks to understand how this FDA-approved treatment can benefit more patients.

Do I need to stop taking my current medications to join the trial?

Yes, you will need to stop taking certain medications to join the trial. Specifically, you must discontinue lamotrigine, clozapine, as-needed anxiolytics (unless benzodiazepines are used regularly), dopamine agonists, and lithium. You should also maintain your usual opioid regimen and consult with the Principal Investigator if you have questions about specific medications.

What is the safety track record for ketamine and Meaning and Purpose therapy?

Research has shown that ketamine, a drug often used for anesthesia, has been studied for its safety in cancer patients. In studies involving individuals with pancreatic cancer and anxiety, researchers examined any unwanted effects from oral ketamine to assess its safety. These studies help identify major side effects.

Ketamine has also shown potential in treating depression in cancer patients, suggesting it might be well-tolerated. However, specific safety information about using ketamine with talk therapy for pancreatic cancer remains limited.

Since this trial is in a later phase, the treatment has typically been tested in earlier studies and is generally considered safe for more people. However, individual reactions can vary, and participating in a trial always involves some level of risk. Prospective participants should discuss any concerns with the trial team or their healthcare provider. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Most treatments for pancreatic cancer focus on chemotherapy, radiation, or surgery. However, the combination of ketamine and Meaning and Purpose (MaP) therapy is unique because it explores a new approach by potentially addressing both the physical and psychological aspects of the disease. Ketamine acts on the brain's NMDA receptors, offering rapid relief of depression and anxiety symptoms, which are common in cancer patients. Meanwhile, MaP therapy helps patients find personal meaning and purpose, which can improve overall well-being. Researchers are excited because this dual approach could enhance both mental health and quality of life for patients in a way that standard treatments do not.

What evidence suggests that this trial's treatments could be effective for demoralization in advanced GI cancer patients?

Studies have shown that ketamine can reduce pain and improve depression symptoms in cancer patients. This is particularly promising for those with gastrointestinal cancers, where pain and emotional distress are common. In this trial, participants will receive either oral or intramuscular ketamine combined with Meaning and Purpose therapy. Research suggests that combining ketamine with talk therapy might ease emotional distress and reduce the need for opioids for pain relief. Previous patients found that ketamine, whether taken orally or by injection, effectively managed pain for several days. The combination of ketamine and Meaning and Purpose therapy aims to address both physical and emotional distress, offering a more comprehensive approach to care. ^{3 6 7 8 9}

Who Is on the Research Team?

Brian T Anderson, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for adults with pancreatic ductal adenocarcinoma who experience significant distress and pain, despite opioid use. Participants must be willing to follow study procedures, speak English/Spanish, avoid certain substances like caffeine and alcohol, and maintain their usual opioid regimen. They should not have had recent severe cardiovascular issues or other specific health conditions that could interfere with the study.

Inclusion Criteria

You must have signs of feeling very down as measured by the Demoralization Scale-II (DS-II).

I can swallow liquid medicine.

I have used opioid painkillers for cancer pain in the past week.

Exclusion Criteria

You have had a serious mental disorder like schizophrenia or bipolar disorder.

Your test results from specific lab tests are within a certain range.

I had a stroke within the last year.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of ketamine combined with Meaning and Purpose (MaP) therapy over approximately 28 days

28 days

4 therapy sessions (2 before and 2 after ketamine administration)

Follow-up

Participants are monitored for safety and effectiveness after treatment

35 days

What Are the Treatments Tested in This Trial?

Interventions

• Ketamine
• Meaning and Purpose therapy

Trial Overview The trial tests if a single dose of oral ketamine combined with talk therapy can reduce demoralization in patients suffering from pancreatic cancer-related pain. It aims to see if this approach lessens psychological distress and decreases reliance on opioids for managing pain.

How Is the Trial Designed?

Group I: Blinded Group B (K-Map) Experimental Treatment 4 Interventions

Participants will receive 0.5mg/kg of Ketamine IM with a placebo oral solution on Day 0/Visit 4 and receive Meaning and Purpose (MaP) therapy 4 times, twice before (between days -13 and -1) ketamine administration, and twice afterward on days 3 (+/- 2 days) and 11 (+/- 3 days). The duration of treatment for ketamine plus MaP (K-MaP) therapy is approximately up to 28 days. Participants will be followed up to 35 days (+/-2 days) after ketamine administration.

Group II: Blinded Group A (K-MaP) Experimental Treatment 4 Interventions

Participants will receive 0.5mg/kg of Ketamine orally with an equivalent quantity of placebo via an intramuscular injection on Day 0/Visit 4 and receive Meaning and Purpose (MaP) therapy 4 times, twice before (between days -13 and -1) ketamine administration, and twice afterward on days 3 (+/- 2 days) and 11 (+/- 3 days). The duration of treatment for ketamine plus MaP (K-MaP) therapy is approximately up to 28 days. Participants will be followed up to 35 days (+/-2 days) after ketamine administration.

Who Is Running the Clinical Trial?

Brian Anderson, MD

Lead Sponsor

Trials

1

Recruited

1+

Published Research Related to This Trial

Patients treated with long-term valproic acid (VPA) showed significantly higher blood ammonia levels and lower blood carnitine levels compared to those not on VPA, indicating potential metabolic disturbances.

The study found a moderate correlation between blood levels of VPA, ammonia, and free carnitine, suggesting that clinicians should monitor both ammonia and carnitine levels in patients on high doses of VPA to manage these adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blood Levels of Ammonia and Carnitine in Patients Treated with Valproic Acid: A Meta-analysis. Yokoyama, S., Sugawara, N., Maruo, K., et al.[2022]

An OKG-enriched diet significantly improved motor activity in healthy rats, as shown by increased movement measured by actimetry and enhanced exploratory behavior in the Y-maze test, compared to control groups.

The study suggests that the stimulant effects of OKG are not linked to increased anxiety or fear, indicating a potential mechanism of action that could contribute to its benefits in nutritional status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ornithine alpha-ketoglutarate supplementation influences motor activity in healthy rats. Moinard, C., Dauge, V., Cynober, L.[2015]

Preventive administration of ornithine alpha-ketoglutarate (OKG) in a rat model of ischemia-reperfusion significantly reduced tissue damage and improved energy production by decreasing levels of pyruvate and lactate, as well as plasma creatine phosphokinase (CPK) levels.

Despite the benefits in reducing tissue damage, OKG treatment did not significantly reduce oxidative stress, as indicated by unchanged glutathione levels and increased thiobarbituric acid reactive substances (TBARS) in treated rats during ischemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of short-term ornithine alpha-ketoglutarate pretreatment on intestinal ischemia-reperfusion in rats. Gonçalves, ES., Rabelo, CM., Prado Neto, AX., et al.[2019]

In a study involving six healthy male subjects, the administration of Ornithine alpha-ketoglutarate (OKG) significantly increased levels of proline and arginine, which are important amino acids, indicating that OKG modifies amino acid metabolism differently than when its components are taken separately.

OKG also led to increased insulin and glucagon levels shortly after administration, suggesting that its effects on amino acid metabolism may influence hormonal responses, although this increase in insulin does not seem to be directly caused by ornithine's action on the pancreas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Action of ornithine alpha-ketoglutarate, ornithine hydrochloride, and calcium alpha-ketoglutarate on plasma amino acid and hormonal patterns in healthy subjects. Cynober, L., Coudray-Lucas, C., de Bandt, JP., et al.[2019]

Dietary supplementation with alpha-ketoglutarate (aKG) significantly reduces symptoms of experimental colitis in mice, including body weight loss and gut inflammation, after being induced by dextran sulfate sodium (DSS).

aKG supplementation improves gut health by enhancing macrophage polarization and restoring epithelial structure, while also shifting metabolism from glycolysis to oxidative processes, suggesting its potential as a preventive or therapeutic option for colitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary Alpha-Ketoglutarate Promotes Epithelial Metabolic Transition and Protects against DSS-Induced Colitis. Tian, Q., Bravo Iniguez, A., Sun, Q., et al.[2021]

The RTT-KaT program, which combines ketamine-assisted therapy with group psychotherapy, was well tolerated by all 128 participants, with no dropouts reported during the 12-week program.

While 49.16% of sessions noted elevated blood pressure post-treatment, most adverse effects were mild and transient, including nausea (12.05%), vomiting (2.52%), headaches (3.35%), and dizziness, indicating a good safety profile for ketamine use in this community setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of intramuscular and sublingual ketamine for psychiatric treatment in the Roots To Thrive ketamine-assisted therapy program: a retrospective chart review. Tsang, VWL., Tao, B., Dames, S., et al.[2023]

A 49-year-old woman with severe treatment-resistant major depression experienced significant improvement after receiving 36 sessions of ketamine intravenous therapy over 10 months, resulting in nearly a 50% reduction in her depressive symptoms.

The case suggests that long-term repeated ketamine therapy could be a viable option for patients with treatment-resistant depression, but further research is needed to determine the best treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous ketamine infusion for a patient with treatment-resistant major depression: a 10-month follow-up. Kwon, JH., Sim, WS., Hong, JP., et al.[2018]

Valproic acid (VPA), while generally safe for treating conditions like epilepsy and bipolar disorder, can cause acute pancreatitis, as demonstrated in a case involving a 66-year-old man with vascular dementia and seizures.

The diagnosis of VPA-induced pancreatitis can be difficult in elderly patients, especially those with dementia, due to non-specific symptoms; therefore, monitoring blood amylase levels is crucial for early detection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute pancreatitis during valproic acid administration in a patient with vascular dementia, epileptic seizures, and psychiatric symptoms: a case report. Yanaga, M., Okamoto, N., Hashimoto, R., et al.[2023]

Alpha-ketoglutarate (alpha-KG) significantly reduces hyperammonemia and hepatotoxicity caused by sodium valproate in rats, as evidenced by decreased levels of ammonia, urea, and serum transaminases.

The protective effects of alpha-KG may be attributed to its role in amino acid metabolism, antioxidant activity, and improved fat metabolism, which together help prevent oxidative damage in the liver.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhancement of circulatory antioxidants by alpha-ketoglutarate during sodium valproate treatment in Wistar rats. Murugesan, V., Subramanian, P.[2018]

In a study of 47 patients with refractory cancer pain, subanesthetic ketamine infusion significantly improved pain levels immediately after treatment and continued to show benefits at 1 and 3 months post-treatment.

Patients reported reductions in worst and current pain scores, indicating that ketamine can be an effective adjuvant therapy for managing difficult-to-treat cancer pain over an extended follow-up period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subanesthetic ketamine in the ambulatory setting for refractory cancer pain: a 6-year retrospective at a cancer center. Chung, M., Benkli, B., Roldan, C., et al.[2021]

Valproic acid (VPA) can cause serious side effects, including acute pancreatitis, as demonstrated in a case of a 6-year-old boy who developed this condition after 3 months of VPA therapy.

The patient's condition improved significantly after stopping VPA, highlighting the importance of monitoring for pancreatitis in children on this medication, especially if they present with abdominal pain and vomiting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Valproic acid-induced acute pancreatitis and multiorgan failure in a child. Yaman, A., Kendirli, T., Odek, C., et al.[2013]

Valproic acid (VPA) can cause rare but severe side effects, such as necro-hemorrhagic pancreatitis, as demonstrated in a case of a 5-year-old boy who developed this condition while on VPA treatment for epilepsy.

The case highlights the potential for fatal outcomes associated with VPA-induced pancreatitis, as seen in this patient and 4 out of 7 similar cases reported in the literature.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Fatal necro-hemorrhagic pancreatitis related to sodium valproate: case report]. Munhoz, RP., dos Santos, ML., Hernández-Fustes, OJ.[2013]

Oral ketamine has shown effectiveness in treating severe depression, including treatment-resistant cases and those with suicidal ideation, based on various studies including randomized controlled trials with doses ranging from 0.25 to 7 mg/kg.

Despite its lower bioavailability (20%-25% reaching the bloodstream), oral ketamine is well tolerated and can be adjusted for individual needs, making it a practical option for depression treatment alongside conventional antidepressants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral Ketamine for Depression, 1: Pharmacologic Considerations and Clinical Evidence. Andrade, C.[2019]

Oral ketamine is a potentially safe and effective treatment for depression, but it requires higher doses (2.0-2.5 mg/kg) compared to intravenous administration due to lower systemic absorption (20%-25%).

Despite its promise as a more accessible and affordable option for treatment, the current literature on oral ketamine is limited, and further research is needed to understand its pharmacokinetics, safety, and efficacy compared to other administration routes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral Ketamine for Depression, 2: Practical Considerations. Andrade, C.[2020]

Valproic acid (VPA) can cause pancreatitis, and this case highlights its occurrence in a patient with end-stage renal disease (ESRD), suggesting that ESRD may increase the risk of this serious side effect.

The report emphasizes the need for healthcare providers to consider the potential for VPA-induced pancreatitis in patients with chronic renal conditions, as they may be more vulnerable to this toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

On the toxicity of valproic-acid. Moreiras Plaza, M., Rodríguez Goyanes, G., Cuiña, L., et al.[2013]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06077487?cond=pancreatic+cancer&aggFilters=status%3A%2Cphase%3A

Ketamine-assisted Therapy for Advanced GI Cancer This study may help researchers learn whether ketamine and talk therapy combined may improve psychosocial distress and pain, as well as decreases opioid ...

2. withpower.com withpower.com/trial/ketamine-talk-therapy-for-pancreatic-cancer-628c8

Ketamine + Talk Therapy for Pancreatic Cancer Ketamine shows promise as a treatment because it has been effective in reducing pain in cancer patients and improving symptoms of depression. This suggests it ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11354190/

The Efficacy of Ketamine for Acute and Chronic Pain in ... Intravenous ketamine, in dosages ranging from 0.1 mg/kg to 0.5 mg/kg, was most efficacious in improving pain scores in patients with cancer for up to 72 h ...

4. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/87/NCT06077487/Prot_SAP_000.pdf

Pilot study of ketamine-assisted talk therapy for ... K-MaP will consist of 4 sessions of Meaning and Purpose (MaP) therapy and a single dose of ketamine on Day 0. Two MaP sessions will occur prior to ketamine ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4517358/

Effects of ketamine, s-ketamine, and MK 801 on proliferation ... Incubating s-ketamine in the pancreatic cancer cells PaTu8988t for 3 h (Fig. 3b) reduced the apoptotic cell fraction phase to 62 % +/− 27 % ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02442739

Ketamine for Preventing Depression in Patients ... The primary purpose of this study is to see if it is safe to give patients with pancreatic or head and neck cancer a low dose of the FDA approved anesthetic ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9910313/

Effects of Ketamine, S-Ketamine and MK 801 on Integrin Beta ... Stimulation with ketamine and MK 801 significantly promoted migration in pancreatic cancer cells, increasing the expression of integrin beta-3.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT05086250

Feasibility Study of Oral Ketamine Versus Placebo for the ... To investigate the safety of oral ketamine in patients with pancreatic cancer and anxiety, which will be assessed by the number of adverse events related to ...

9. e-jhpc.org e-jhpc.org/journal/view.html?doi=10.14475/kjhpc.2016.19.3.249

Factors Associated with Ketamine Use in Pancreatic ... In this retrospective study, ketamine was frequently considered in patients with severe pain, requiring higher amount of opioid.