Oral Squamous Cell CarcinomaNCT05024383
Dissecting the Heterogeneity of Oral Cancer Pain
A study testing Chemical sensitivity and Mechanical sensitivity in people with Oral Squamous Cell Carcinoma, run by NYU College of Dentistry at 1 site in United States.
Trial summary
Oral squamous cell carcinoma (SCC) produces a higher prevalence and more severe pain than all other cancers. Orofacial pain is one of the most common initial symptoms of oral cancer and often leads to the diagnosis of oral cancer. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Oral Squamous Cell Carcinoma
- What is being tested?
- Chemical sensitivity and Mechanical sensitivity
- Type of treatment
- Pill or oral medicine
- How many people
- 80 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Sep 2021to Dec 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Biopsy-proven squamous cell carcinoma (SCC) of the oral cavity that requires surgical resection
- Lesion is at least 1 cm in greatest surface dimension
- In good general health as evidenced by medical history
Who cannot join
- History of prior surgical, chemotherapeutic, or radiation treatment for head and neck cancer
- Pregnancy or lactation
- Clinically and/or histologically proven oral pre-cancer, oral cancer
- Pregnancy or lactation
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
New York University College of Dentistry
New York, New York, 10010
Brian Schmidt, bls322@nyu.edu
About this study
Oral squamous cell carcinoma (SCC) produces a higher prevalence and more severe pain than all other cancers. Orofacial pain is one of the most common initial symptoms of oral cancer and often leads to the diagnosis of oral cancer. However, the character, severity, and unique features of oral cancer widely differ between patients. There is currently no effective and lasting treatment available to alleviate suffering from oral cancer pain.
A significant obstacle to effectively treating cancer pain is that the relative contributions of nociceptive mediators and their mechanisms of action (i.e., responsible receptors) are largely unknown. There is, therefore, a critical need to define the neurobiologic mechanisms responsible for oral cancer pain. Without such information, the promise of non-opioid therapy for the treatment of oral cancer pain will remain unfulfilled.
The primary objective of this study is to define and quantify the phenotype of oral cancer pain in patients, by comparing mechano- and chemosensitivity in oral cancer patients with healthy subjects. Pain will be stimulated on the site of cancer in 40 oral cancer patients and on the tongue in 40 healthy volunteers utilizing chemical sensitivity and mechanical sensitivity tests.
Read the detailed description
Oral squamous cell carcinoma (SCC) is the sixth most common cancer worldwide. The majority of patients with oral SCC suffer from severe, chronic, function-induced pain. Despite the severity of pain in many patients, the presentation of oral cancer pain is variable. Opioids are the only treatment available for oral cancer pain. Opioids are often ineffective and associated with tolerance, constipation, somnolence, respiratory depression, and addiction, which is now a national crisis.
The current hypothesis for the etiology of oral cancer pain, which is based on clinical studies utilizing questionnaires and preclinical studies, is that cancer cells and cells within the microenvironment produce mediators that activate and sensitize nociceptors. Published and preliminary data indicate that cancer-secreted mediators induce mechano- and chemosensitivity. For example, preliminary clinical studies demonstrate that oral cancer patients experience preoperative sensitivity to capsaicin (i.e., chemosensitivity) and report greater functional (i.e., mechanosensitivity) pain. Capsaicin activates transient receptor potential vanilloid 1 (TRPV1). TRPV1 is activated by temperatures above 43°C and endogenous lipid metabolic products. Mice deficient in TRPV1 respond to mechanical stimuli, suggesting that TRPV1 is not involved in the detection of mechanical stimulation. By contrast, TRP ankyrin repeat 1 (TRPA1), co-localized with TRPV1, is responsive to mechanical stimuli, in addition to irritants such as allyl isothiocyanate (AITC). Both TRPV1 and TRPA1 have been reported to play important roles in orofacial pain. Improved knowledge of the contribution of TRPV1 and TRPA1 to oral cancer pain holds considerable promise for the development of novel, non-opioid treatment strategies that specifically address the unique pain experience of individual patients.
There is a lack of published data characterizing the sensory phenotype of tumor-related cancer pain, which has significant implications for understanding the underlying pathophysiological mechanisms of cancer pain. Quantitative sensory testing can provide insight into the mechanism(s) responsible for pain. In this proposal, we will test our hypothesis that the quality of pain experienced by oral cancer patients is dependent on the level of activation of specific channels on nociceptors. We will perform mechanical (von Frey testing) and chemical sensitivity tests (sensitivity to capsaicin, TRPV1 agonist, and AITC (TRPA1 agonist) on oral cancer patients, and compare the sensitivities to healthy subjects. For cancer patients, we will administer the validated University of California San Francisco (UCSF) Oral Cancer Pain Questionnaire to evaluate the correlation between mechanical and chemical thresholds with relevant aspects of pain.
We propose that the quality of pain experienced by oral cancer patients is quantifiable and dependent on the level of sensitization and activation of specific channels on nociceptors.
- Conditions
- Oral Squamous Cell Carcinoma
- Being tested
- Chemical sensitivity, Mechanical sensitivity
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Chemical sensitivityOther
Chemical sensitivity will be evaluated with paper taste strips embedded with varying concentrations of capsaicin solutions (activates TRPV1) and allyl isothiocyanate solutions (activates TRPA1) applied to the tongues of healthy subjects and site of cancer in oral cancer patients.
Mechanical sensitivityOther
Mechanical sensitivity will be evaluated via von Frey filaments applied to the tongues of healthy subjects and and site of cancer in oral cancer patients.
What is being measured
The primary outcome is the main question the study is designed to answer.
Mechanical Sensitivity
Pain will be evaluated using verbal feedback from participants for mechanical sensitivity testing.
Measured: Baseline visit
Chemical Sensitivity
Pain will be evaluated using a visual analogue scale for chemical sensitivity testing.
Measured: Baseline visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Aug 2021
- Study start30 Sep 2021
- Primary completionDec 2025 (estimated)
- Study completionDec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Oral Squamous Cell CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single arm study design with group comparisons
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- NYU College of Dentistry
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Brian L. Schmidt, NYU College of Dentistry
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05024383
- Sponsor's protocol ID
- i21-00964
- Status last verified
- Sep 2022
- First submitted
- 23 Aug 2021
- Last updated
- 28 Sep 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Schmidt BL, Hamamoto DT, Simone DA, Wilcox GL. Mechanism of cancer pain. Mol Interv. 2010 Jun;10(3):164-78. doi: 10.1124/mi.10.3.7.
PubMed 20539035Schmidt BL. The neurobiology of cancer pain. Neuroscientist. 2014 Oct;20(5):546-62. doi: 10.1177/1073858414525828. Epub 2014 Mar 24.
PubMed 24664352Yang F, Zheng J. Understand spiciness: mechanism of TRPV1 channel activation by capsaicin. Protein Cell. 2017 Mar;8(3):169-177. doi: 10.1007/s13238-016-0353-7. Epub 2017 Jan 2.
PubMed 28044278Jordt SE, Bautista DM, Chuang HH, McKemy DD, Zygmunt PM, Hogestatt ED, Meng ID, Julius D. Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1. Nature. 2004 Jan 15;427(6971):260-5. doi: 10.1038/nature02282. Epub 2004 Jan 7.
PubMed 14712238
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dissecting the Heterogeneity of Oral Cancer Pain
- ClinicalTrials.gov ID
- NCT05024383
- Acronym / sponsor ID
- i21-00964
- Conditions
- Oral Squamous Cell Carcinoma
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- NYU College of DentistryUniversity, hospital or other
- Study start
- 30 Sep 2021 (actual)
- Primary completion
- Dec 2025 (estimated)
- Study completion
- Dec 2025 (estimated)
- First posted
- 27 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Oral squamous cell carcinoma (SCC) produces a higher prevalence and more severe pain than all other cancers. Orofacial pain is one of the most common initial symptoms of oral cancer and often leads to the diagnosis of oral cancer. However, the character, severity, and unique features of oral cancer widely differ between patients. There is currently no effective and lasting treatment available to alleviate suffering from oral cancer pain.
A significant obstacle to effectively treating cancer pain is that the relative contributions of nociceptive mediators and their mechanisms of action (i.e., responsible receptors) are largely unknown. There is, therefore, a critical need to define the neurobiologic mechanisms responsible for oral cancer pain. Without such information, the promise of non-opioid therapy for the treatment of oral cancer pain will remain unfulfilled.
The primary objective of this study is to define and quantify the phenotype of oral cancer pain in patients, by comparing mechano- and chemosensitivity in oral cancer patients with healthy subjects. Pain will be stimulated on the site of cancer in 40 oral cancer patients and on the tongue in 40 healthy volunteers utilizing chemical sensitivity and mechanical sensitivity tests.
Detailed description
Oral squamous cell carcinoma (SCC) is the sixth most common cancer worldwide. The majority of patients with oral SCC suffer from severe, chronic, function-induced pain. Despite the severity of pain in many patients, the presentation of oral cancer pain is variable. Opioids are the only treatment available for oral cancer pain. Opioids are often ineffective and associated with tolerance, constipation, somnolence, respiratory depression, and addiction, which is now a national crisis.
The current hypothesis for the etiology of oral cancer pain, which is based on clinical studies utilizing questionnaires and preclinical studies, is that cancer cells and cells within the microenvironment produce mediators that activate and sensitize nociceptors. Published and preliminary data indicate that cancer-secreted mediators induce mechano- and chemosensitivity. For example, preliminary clinical studies demonstrate that oral cancer patients experience preoperative sensitivity to capsaicin (i.e., chemosensitivity) and report greater functional (i.e., mechanosensitivity) pain. Capsaicin activates transient receptor potential vanilloid 1 (TRPV1). TRPV1 is activated by temperatures above 43°C and endogenous lipid metabolic products. Mice deficient in TRPV1 respond to mechanical stimuli, suggesting that TRPV1 is not involved in the detection of mechanical stimulation. By contrast, TRP ankyrin repeat 1 (TRPA1), co-localized with TRPV1, is responsive to mechanical stimuli, in addition to irritants such as allyl isothiocyanate (AITC). Both TRPV1 and TRPA1 have been reported to play important roles in orofacial pain. Improved knowledge of the contribution of TRPV1 and TRPA1 to oral cancer pain holds considerable promise for the development of novel, non-opioid treatment strategies that specifically address the unique pain experience of individual patients.
There is a lack of published data characterizing the sensory phenotype of tumor-related cancer pain, which has significant implications for understanding the underlying pathophysiological mechanisms of cancer pain. Quantitative sensory testing can provide insight into the mechanism(s) responsible for pain. In this proposal, we will test our hypothesis that the quality of pain experienced by oral cancer patients is dependent on the level of activation of specific channels on nociceptors. We will perform mechanical (von Frey testing) and chemical sensitivity tests (sensitivity to capsaicin, TRPV1 agonist, and AITC (TRPA1 agonist) on oral cancer patients, and compare the sensitivities to healthy subjects. For cancer patients, we will administer the validated University of California San Francisco (UCSF) Oral Cancer Pain Questionnaire to evaluate the correlation between mechanical and chemical thresholds with relevant aspects of pain.
We propose that the quality of pain experienced by oral cancer patients is quantifiable and dependent on the level of sensitization and activation of specific channels on nociceptors.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Model description
- Single arm study design with group comparisons
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Biopsy-proven squamous cell carcinoma (SCC) of the oral cavity that requires surgical resection
- Lesion is at least 1 cm in greatest surface dimension
- In good general health as evidenced by medical history
Key exclusion criteria (4 listed)
- History of prior surgical, chemotherapeutic, or radiation treatment for head and neck cancer
- Pregnancy or lactation
- Clinically and/or histologically proven oral pre-cancer, oral cancer
- Pregnancy or lactation
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Chemical sensitivityChemical sensitivity will be evaluated with paper taste strips embedded with varying concentrations of capsaicin solutions (activates TRPV1) and allyl isothiocyanate solutions (activates TRPA1) applied to the tongues of healthy subjects and site of cancer in oral cancer patients. | Other | – |
| Mechanical sensitivityMechanical sensitivity will be evaluated via von Frey filaments applied to the tongues of healthy subjects and and site of cancer in oral cancer patients. | Other | – |
Primary outcome
Mechanical Sensitivity
Time frame: Baseline visit
Pain will be evaluated using verbal feedback from participants for mechanical sensitivity testing.
Chemical Sensitivity
Time frame: Baseline visit
Pain will be evaluated using a visual analogue scale for chemical sensitivity testing.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2022.
- Background: PubMed 20539035Schmidt BL, Hamamoto DT, Simone DA, Wilcox GL. Mechanism of cancer pain. Mol Interv. 2010 Jun;10(3):164-78. doi: 10.1124/mi.10.3.7.
- Background: PubMed 24664352Schmidt BL. The neurobiology of cancer pain. Neuroscientist. 2014 Oct;20(5):546-62. doi: 10.1177/1073858414525828. Epub 2014 Mar 24.
- Background: PubMed 28044278Yang F, Zheng J. Understand spiciness: mechanism of TRPV1 channel activation by capsaicin. Protein Cell. 2017 Mar;8(3):169-177. doi: 10.1007/s13238-016-0353-7. Epub 2017 Jan 2.
- Background: PubMed 14712238Jordt SE, Bautista DM, Chuang HH, McKemy DD, Zygmunt PM, Hogestatt ED, Meng ID, Julius D. Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1. Nature. 2004 Jan 15;427(6971):260-5. doi: 10.1038/nature02282. Epub 2004 Jan 7.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Chemical sensitivity and Mechanical sensitivity in people with Oral Squamous Cell Carcinoma, run by NYU College of Dentistry at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 28 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Brian Schmidt, MD, DDS, PhD (212-995-4843, bls322@nyu.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mechanical Sensitivity (time frame: Baseline visit). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05024383, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Sep 2022.