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

Trial Summary

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 data supports the idea that Ketamine + Talk Therapy for Pancreatic Cancer is an effective treatment?

The available research does not provide any data specifically supporting the effectiveness of Ketamine + Talk Therapy for Pancreatic Cancer. The studies mentioned focus on other compounds like ornithine alpha-ketoglutarate and alpha-ketoglutarate, which are not related to ketamine or its use in cancer treatment. Therefore, there is no evidence from the provided information to support the effectiveness of this treatment for pancreatic cancer. ^{1 2 3 4 5}

What safety data exists for Ketamine and talk therapy in treating pancreatic cancer?

The provided research does not contain safety data for Ketamine or talk therapy in treating pancreatic cancer. It focuses on the adverse effects of valproic acid, particularly pancreatitis, which is unrelated to Ketamine or the specified treatment. ^{6 7 8 9 10}

Is the drug used in Ketamine + Talk Therapy for Pancreatic Cancer a promising treatment?

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 could help people with pancreatic cancer by managing pain and potentially improving their mental health. ^{11 12 13 14 15}

What is the purpose of this trial?

This clinical trial evaluates whether it is possible to use a single dose of ketamine in combination with talk therapy to treat moderate to severe demoralization in patients with stage 3 or 4 gastrointestinal (GI) cancers who take opioids for cancer-related pain. Advanced stage gastrointestinal (GI) cancer patients often suffer from high rates of psychosocial distress and pain. Symptoms of anxiety are highly prevalent among gastrointestinal (GI) cancers patients. While opioid analgesia (pain reliever) succeeds in managing some symptoms, chronic opioid therapy is associated with significant adverse effects, underscoring a need to identify alternative interventions in the treatment of cancer associated pain. GI cancer patients frequently suffer from existential distress, and demoralization is a form of existential distress that is common among people with serious medical illnesses. Demoralization is characterized by poor coping with stressful events, and a loss of meaning and purpose in life. Talk therapy is a form of psychological treatment during which patients discuss problems, thoughts, and feelings. Ketamine has demonstrated efficacy for the treatment of depression, suicidality, and pain in non-cancer patients. This study may help researchers learn whether ketamine and talk therapy combined may improve psychosocial distress and pain, as well as decreases opioid analgesic use in patients with advanced GI cancer who take opioids for cancer-related pain.

Research Team

Brian T Anderson, MD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Ornithine alpha-ketoglutarate supplementation influences motor activity in healthy rats. [2015]

2. Poland pubmed.ncbi.nlm.nih.gov

Enhancement of circulatory antioxidants by alpha-ketoglutarate during sodium valproate treatment in Wistar rats. [2018]

3. Brazil pubmed.ncbi.nlm.nih.gov

Effect of short-term ornithine alpha-ketoglutarate pretreatment on intestinal ischemia-reperfusion in rats. [2019]

4. United States 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. [2019]

5. Germany pubmed.ncbi.nlm.nih.gov

Dietary Alpha-Ketoglutarate Promotes Epithelial Metabolic Transition and Protects against DSS-Induced Colitis. [2021]

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

Valproic acid-induced acute pancreatitis and multiorgan failure in a child. [2013]

7. Korea (South) pubmed.ncbi.nlm.nih.gov

Blood Levels of Ammonia and Carnitine in Patients Treated with Valproic Acid: A Meta-analysis. [2022]

8. Germany pubmed.ncbi.nlm.nih.gov

[Fatal necro-hemorrhagic pancreatitis related to sodium valproate: case report]. [2013]

9. Germany pubmed.ncbi.nlm.nih.gov

On the toxicity of valproic-acid. [2013]

10. England 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. [2023]

11. England 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. [2023]

12. England pubmed.ncbi.nlm.nih.gov

Intravenous ketamine infusion for a patient with treatment-resistant major depression: a 10-month follow-up. [2018]

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

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

14. England pubmed.ncbi.nlm.nih.gov

Subanesthetic ketamine in the ambulatory setting for refractory cancer pain: a 6-year retrospective at a cancer center. [2021]

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

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