Ketamine Oral Rinse for Mucositis

Overseen By Lead Nurse

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Oklahoma

Disqualifiers: Other malignancy, Schizophrenia, Uncontrolled diseases, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 30

Duration: 6 months

62 Participants Needed

Trial Summary

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What evidence supports the effectiveness of the drug ketamine oral rinse for mucositis?

Research suggests that ketamine, when used as a mouthwash, can be a safe and effective way to relieve pain from mucositis, a painful inflammation and ulceration of the mouth lining. ^{1 2 3 4 5}

Is ketamine oral rinse safe for humans?

Research shows that oral ketamine, used in different forms like lollipops for children, is generally safe and well-tolerated. Common side effects of ketamine include a feeling of detachment from reality and increased blood pressure, but these can vary depending on how the drug is taken. ^{1 3 6 7 8}

How does the drug ketamine oral rinse for mucositis differ from other treatments?

Ketamine oral rinse is unique because it uses ketamine, a drug known for its anesthetic and pain-relieving properties, in a topical form to potentially alleviate pain and inflammation in the mouth, which is different from standard treatments that may not use this mechanism or route of administration. ^{9 10 11 12 13}

What is the purpose of this trial?

This 2-arm phase II study proposes to determine the efficacy of ketamine oral rinse in pain relief from mucositis in head and neck cancer patients undergoing radiation treatment.

Research Team

Rusha Patel, MD

Principal Investigator

OU Health Stephenson Cancer Center

Eligibility Criteria

This trial is for head and neck cancer patients who are experiencing painful mouth ulcers (mucositis) due to radiation treatment. Specific eligibility criteria details were not provided, so interested individuals should inquire about the full inclusion and exclusion requirements.

Inclusion Criteria

I have had radiation treatment for my head or neck cancer.

I am receiving radiation or chemoradiation for head and neck cancer.

Written informed consent signed and dated by the patient prior to the performance of the study-specific procedure

Exclusion Criteria

I am unable to sign a consent form.

I am not allergic to ketamine.

Women who are pregnant, nursing, or who plan to become pregnant while in the study and for at least 6 months after the last administration of study treatment

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Patients undergo radiation or concurrent chemoradiation as part of their treatment plan

6 months

Weekly visits for radiation treatment

Treatment

Participants receive ketamine oral rinse or unmedicated oral rinse 4 times a day if they develop oral mucositis

6 months

Daily use of oral rinse, weekly monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including quality of life and pain response

4 weeks

Up to 30 days after treatment

Treatment Details

Interventions

• Ketamine

Trial Overview The study is testing if a ketamine oral rinse can relieve pain from mucositis compared to a placebo. It's a phase II trial with two groups: one receiving the ketamine rinse and the other receiving an inactive substance.

Participant Groups

Group I: Intervention Group Experimental Treatment 1 Intervention

Topical ketamine in syrup + any standard treatment for oral mucositis.

Group II: Control Group Placebo Group 1 Intervention

Topical unmedicated syrup base + any standard treatment for oral mucositis.

Ketamine is already approved in 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

Who Is Running the Clinical Trial?

University of Oklahoma

Lead Sponsor

Trials

484

Recruited

95,900+

Findings from Research

In a study involving twelve healthy unmedicated cats, the combination of ketamine and midazolam showed that midazolam doses between 0.05 mg/kg and 0.5 mg/kg had beneficial effects, such as reducing muscle rigidity and nociceptive responses, without significantly delaying recovery compared to ketamine alone.

However, higher doses of midazolam (5.0 mg/kg) prolonged recovery times and led to adverse behavioral effects like restlessness and vocalization, indicating a need for careful dosing to avoid negative outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of intravenous administration of variable-dose midazolam after fixed-dose ketamine in healthy awake cats. Ilkiw, JE., Suter, CM., McNeal, D., et al.[2019]

Oral transmucosal ketamine (OTK) was found to be an effective and well-accepted method for sedation in 25 children, facilitating procedures like intravenous line insertion.

OTK, administered as lollipops, slightly increased gastric volumes but did not alter gastric pH, indicating it is a safe preoperative medication for pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral transmucosal ketamine: an effective premedication in children. Cioacă, R., Canavea, I.[2019]

In a study involving 41 healthy children under 36 months, the combination of oral midazolam and ketamine (MK) significantly improved cooperative behavior during dental treatment compared to midazolam alone (MS) or no sedation (PS).

No immediate or post-discharge side effects were observed in the groups receiving midazolam and ketamine, indicating that this sedation method is safe for young children undergoing dental procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined oral midazolam-ketamine better than midazolam alone for sedation of young children: a randomized controlled trial. Moreira, TA., Costa, PS., Costa, LR., et al.[2022]

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]

A review of 41 treatment arms from 21 studies found that ketamine formulations that maximize first pass metabolism and delay the time to peak concentration (Tmax) are associated with better safety and tolerability, particularly in reducing side effects like dissociation and increased blood pressure.

The study revealed strong correlations between the ketamine:norketamine ratio and both dissociation ratings and blood pressure changes, suggesting that careful formulation can help minimize adverse effects while maintaining the antidepressant efficacy of ketamine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of formulation and route of administration on ketamine's safety and tolerability: systematic review. Glue, P., Russell, B., Medlicott, NJ.[2021]

An extended release oral ketamine tablet was found to be safe and well tolerated in a study of seven patients with treatment-resistant depression/anxiety, with no significant changes in vital signs and only one brief report of dissociation.

All patients experienced over 50% improvements in mood ratings over 96 hours, suggesting that while the onset of mood improvement is slightly delayed compared to injectable forms, this oral formulation could be a promising option for treating resistant depression and anxiety disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of extended release ketamine tablets in patients with treatment-resistant depression and anxiety: open label pilot study. Glue, P., Medlicott, NJ., Neehoff, S., et al.[2022]

In a study involving 9 children with refractory convulsive status epilepticus (RSE), intravenous ketamine was found to be effective in resolving RSE in 6 of the patients, demonstrating its potential as a treatment option.

The treatment was deemed safe, as none of the patients experienced serious adverse events, suggesting that ketamine could be a viable alternative for children who do not respond to conventional anesthetics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of ketamine in refractory status epilepticus in children. Rosati, A., L'Erario, M., Ilvento, L., et al.[2022]

Vitamin K1 (VK1) can be effectively delivered through the skin using lipid vesicle formulations like transfersomes and ethosomes, which enhance its accumulation and permeation.

Nebulizing these vesicles further increases VK1 accumulation in the skin, making transfersomes a promising option for localized skin treatment with minimal systemic absorption.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nanocarriers to Enhance the Accumulation of Vitamin K1 into the Skin. Campani, V., Biondi, M., Mayol, L., et al.[2018]

References

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

Ketamine mouthwash for mucositis pain. [2022]

2. England pubmed.ncbi.nlm.nih.gov

The effect of intravenous administration of variable-dose midazolam after fixed-dose ketamine in healthy awake cats. [2019]

3. France pubmed.ncbi.nlm.nih.gov

Oral transmucosal ketamine: an effective premedication in children. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Combined oral midazolam-ketamine better than midazolam alone for sedation of young children: a randomized controlled trial. [2022]

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

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

6. Germany pubmed.ncbi.nlm.nih.gov

Influence of formulation and route of administration on ketamine's safety and tolerability: systematic review. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of extended release ketamine tablets in patients with treatment-resistant depression and anxiety: open label pilot study. [2022]

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

Efficacy and safety of ketamine in refractory status epilepticus in children. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Vitamin K distribution in rat tissues: dietary phylloquinone is a source of tissue menaquinone-4. [2019]

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

Nanocarriers to Enhance the Accumulation of Vitamin K1 into the Skin. [2018]

11. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Effect of different supplies of vitamin K on the biotransformation of amidopyrine and benzoic acid in the rat]. [2015]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Newly developed model for vitamin K deficiency in germfree mice. [2007]

13. Australia pubmed.ncbi.nlm.nih.gov

Cutaneous allergic reaction to intramuscular vitamin K1. [2019]