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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a ketamine oral rinse can reduce pain from mucositis, a painful mouth condition, in individuals with head and neck cancer undergoing radiation treatment. Participants will receive either the ketamine rinse or a placebo (a non-medicated syrup) alongside standard treatments for mucositis. The trial seeks individuals with head and neck cancer who have experienced painful mouth sores due to radiation and are currently receiving radiation treatment. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group.

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.

Is there any evidence suggesting that ketamine oral rinse is likely to be safe for humans?

Research has shown that ketamine mouth rinses safely ease pain from mucositis. Studies have found that ketamine mouthwash significantly reduces pain without harmful side effects. Patients reported their pain dropping from a level of 7 out of 10 to 3 out of 10, marking a significant improvement. Additionally, ketamine mouthwash is well-tolerated, making it a promising option for managing pain from mucositis in head and neck cancer patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for oral mucositis, such as mouthwashes and gels, work by soothing inflammation and promoting healing over time. However, the ketamine oral rinse is unique because it uses ketamine, a well-known anesthetic, in a topical form to potentially provide rapid pain relief directly at the source. This approach is different from standard care, offering a new mechanism of action by targeting pain pathways in the mouth. Researchers are excited about this treatment because it could offer quicker relief and improve the quality of life for patients suffering from this painful condition.

What evidence suggests that ketamine oral rinse might be an effective treatment for mucositis?

Research has shown that ketamine mouthwash can greatly reduce pain from mucositis, a painful condition in the mouth and throat. In one study, patients experienced significant pain relief just minutes after using the mouthwash. Another study found that half of the patients with severe mouth or throat pain, unresponsive to other treatments, felt better after using ketamine mouthwash. Additionally, a different study noted a significant drop in pain levels after just one hour of use, with further improvement over three days. In this trial, participants in the intervention group will receive topical ketamine in syrup, while the control group will receive a topical unmedicated syrup base. These results suggest that ketamine mouthwash could be a promising way to manage mucositis pain. ^{2 6 7 8 9}

Who Is on the Research Team?

Rusha Patel, MD

Principal Investigator

OU Health Stephenson Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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 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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10105995/

Efficacy of ketamine mouthwash in the management of oral ... The patient was treated with ketamine mouthwash at a strength of 20 mg/5 mL, experienced significant pain relief within minutes of ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05331131

NCT05331131 | Efficacy of Ketamine Mouthwash in the ... This study has not yet reported results (20). Another recently published randomized controlled trial studied the efficacy of ketamine mouthwash for chemotherapy ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2386401X15000079

Treatment with ketamine mouthwashes with and without ... Of the 20 patients, 16 had orofacial or mucositis pain refractory to a mixture of lidocaine and opioids. The effectiveness of ketamine mouthwash was 50% (8/16 ...

4. researchgate.net researchgate.net/publication/369965113_Efficacy_of_ketamine_mouthwash_in_the_management_of_oral_and_pharyngeal_toxicity_associated_with_head_and_neck_chemoradiotherapy_protocol_for_a_phase_II_Simon's_two-stage_trial

Protocol for a phase II, Simon's two-stage trial Ketamine oral rinse has shown promising results in a few studies in adults. This randomized, double‐blind placebo‐controlled trial aimed to test the ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/28190158/

Treatment of severe mucositis pain with oral ketamine ... A statistically significant reduction in pain scores of 2 and 3 points was achieved after 1 h and 3 days, respectively (p < 0.0001, p = 0.0003). Pain scores ...

6. astctjournal.org astctjournal.org/article/S1083-8791(15)01854-6/fulltext

Treatment of Severe Mucositis Pain with Oral Ketamine ... Oral ketamine mouthwashes provide a safe and feasible alternative for mucositis pain. Ketamine use resulted in a clinically meaningful reduction in pain scores.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5500907/

Treatment of severe mucositis pain with oral ketamine ... Ketamine mouthwashes resulted in clinically meaningful and statistically significant reduction in pain scores, have an acceptable safety profile, and can be a ...

8. liebertpub.com liebertpub.com/doi/10.1089/jpm.2009.0198

Ketamine Mouthwash for Mucositis Pain The study stated that the ketamine mouthwash showed efficacy in the absence of adverse effects. The patients pain score decreased from 7/10 to 3/10 within ...

9. careacross.com careacross.com/clinical-trials/trial/NCT06660017

Head and Neck Cancer Patients With Oral Mucositis ... Summary: 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 ...