Defining TRPV4 Contribution of Schwann Cells to Oral Cancer Pain

NCT07095608 | Recruiting

• 2 other identifiers: 25-005311K23DE034496-01
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective study involving human participants. Pressure and stretch sensitivity measures between oral cancer patients and healthy subjects will be compared. Pain stimulation will be conducted on the site of the cancer in 40 oral cancer patients, and on the tongue in 40 healthy volunteers, using pressure and stretch sensitivity tests.

Conditions

Oral Cancer; Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (2)

• Pressure sensitivity

  Pressure pain thresholds will be measured in kilopascals with a digital pressure algometer. The average of three measurements will be used to determine each threshold. Lower thresholds signify higher pain levels.

  Baseline

• Stretch sensitivity

  Stretch sensitivity will be evaluated by assessing pain or discomfort associated with tongue range of motions (tongue protrusion, tongue elevation, right lateralization and left lateralization).To measure stretch sensitivity, visual analog scale (VAS) scores for participants' pain associated with tongue stretching will be recorded. Participants will perform tongue range of motions (ROM): protrusion, elevation, and right and left lateralization, and they will rate their sensitivity on the VAS scale after holding each position for five seconds. Subjects will also rate the quality of their pain. Stretch sensitivity will be defined as the sum of VAS scores for protrusion, elevation, and right and left lateralization. The VAS goes from 0-100, 0 representing no pain and 100 representing the most intense pain imaginable.

  Baseline

Secondary Outcomes (1)

• To determine whether patients with lower pressure pain thresholds report higher pain scores on the visual analog scale after tongue stretching.

  Baseline

Study Arms (2)

Oral Cancer Subjects

EXPERIMENTAL

Oral cancer patients will be tested for pressure and stretch sensitivity. Pressure sensitivity will be evaluated with a digital pressure algometer by applying the probe tip to the site of cancer in oral cancer patients. Stretch sensitivity will be evaluated with visual analog scale recording of pain scores associated with tongue range of motions in oral cancer patients.

Behavioral: Pressure and stretch sensitivity testing

Healthy Subjects

ACTIVE COMPARATOR

Healthy subjects will be tested for pressure and stretch sensitivity. Pressure sensitivity will be evaluated with a digital pressure algometer by applying the probe tip to the tongues of healthy subjects. Stretch sensitivity will be evaluated with visual analog scale recording of pain scores associated with tongue range of motions in healthy subjects.

Behavioral: Pressure and stretch sensitivity testing

Interventions

Pressure and stretch sensitivity testing BEHAVIORAL

We will measure pressure sensitivity by applying gradual pressure (50 kPa/s) at the site of testing using a digital pressure algometer. In healthy subjects, we will perform these measurements on the lateral tongue on the left and the right side. In cancer patients, we will first test on the unaffected contralateral matched site and then at the site of the cancer. We will define pressure sensitivity as the mean of three threshold measurements. For measuring stretch sensitivity, we will use a visual analog scale (VAS) recording of pain scores associated with tongue stretching. Participants will be asked to perform tongue range of motions (ROM): protrusion, elevation, right and left lateralization, and rate sensitivity score on the VAS scale after holding the tongue in position for five seconds. We will define stretch sensitivity as the sum of VAS scores for protrusion, elevation, right and left lateralization.

Healthy Subjects; Oral Cancer Subjects

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For healthy subjects to be eligible to participate in this study, an individual must meet all of the following criteria:
• Provide signed and dated informed consent form
• Willing to comply with all study procedures and be available for the duration of the study
• Male or female, at least 18 years of age
• In good general health as evidenced by medical history
• For oral cancer patients to be eligible to participate in this study, an individual must meet all of the following criteria:
• Provide signed and dated informed consent form
• Willing to comply with all study procedures and be available for the duration of the study
• Male or female, at least 18 years of age
• Biopsy-proven squamous cell carcinoma (SCC) of the oral cavity that requires surgical resection
• Lesion is at least 1 cm in greatest surface dimension

You may not qualify if:

• Healthy subjects who meet any of the following criteria will be excluded from participation in this study:
• Clinically and/or histologically proven oral pre-cancer, oral cancer
• Pregnancy or lactation (Female subjects of child-bearing potential will have a rapid urine pregnancy test)
• Anything that would place the individual at increased risk or preclude the individual's full compliance with or completion of the study.
• Oral cancer patients who meet any of the following criteria will be excluded from participation in this study:
• History of prior surgical, chemotherapeutic, or radiation treatment for head and neck cancer
• Pregnancy or lactation
• Anything that would place the individual at increased risk or preclude the individual's full compliance with or completion of the study.
• For participants with impaired kidney function (chronic kidney/renal disease) who wish to participate in the proposed research study, consultation with their primary care provider will be done prior to enrollment to determine safety

Sponsors & Collaborators

• New York University: lead
• National Institute of Dental and Craniofacial Research (NIDCR): collaborator

Study Sites (1)

NYU College of Dentistry

New York, New York, 10010, United States

RECRUITING

Related Publications (9)

• Gormley M, Creaney G, Schache A, Ingarfield K, Conway DI. Reviewing the epidemiology of head and neck cancer: definitions, trends and risk factors. Br Dent J. 2022 Nov;233(9):780-786. doi: 10.1038/s41415-022-5166-x. Epub 2022 Nov 11.

  PMID: 36369568 BACKGROUND

• Viet CT, Schmidt BL. Biologic mechanisms of oral cancer pain and implications for clinical therapy. J Dent Res. 2012 May;91(5):447-53. doi: 10.1177/0022034511424156. Epub 2011 Oct 4.

  PMID: 21972258 BACKGROUND

• Szczot M, Liljencrantz J, Ghitani N, Barik A, Lam R, Thompson JH, Bharucha-Goebel D, Saade D, Necaise A, Donkervoort S, Foley AR, Gordon T, Case L, Bushnell MC, Bonnemann CG, Chesler AT. PIEZO2 mediates injury-induced tactile pain in mice and humans. Sci Transl Med. 2018 Oct 10;10(462):eaat9892. doi: 10.1126/scitranslmed.aat9892.

  PMID: 30305456 BACKGROUND

• Nilius B, Voets T. The puzzle of TRPV4 channelopathies. EMBO Rep. 2013 Feb;14(2):152-63. doi: 10.1038/embor.2012.219. Epub 2013 Jan 11.

  PMID: 23306656 BACKGROUND

• Mikesell AR, Isaeva E, Schulte ML, Menzel AD, Sriram A, Prahl MM, Shin SM, Sadler KE, Yu H, Stucky CL. Increased keratinocyte activity and PIEZO1 signaling contribute to paclitaxel-induced mechanical hypersensitivity. Sci Transl Med. 2024 Dec 11;16(777):eadn5629. doi: 10.1126/scitranslmed.adn5629. Epub 2024 Dec 11.

  PMID: 39661703 BACKGROUND

• Suzuki M, Mizuno A, Kodaira K, Imai M. Impaired pressure sensation in mice lacking TRPV4. J Biol Chem. 2003 Jun 20;278(25):22664-8. doi: 10.1074/jbc.M302561200. Epub 2003 Apr 13.

  PMID: 12692122 BACKGROUND

• Mulpuri Y, Tu NH, Inoue K, Harden G, Nicholson SJ, Seenauth A, Huang Y, Escobar KG, Moayedi Y, Bunnett NW, Albertson DG, Schmidt BL. TRPV4 activation in Schwann cells mediates mechanically induced pain of oral cancer. Front Pain Res (Lausanne). 2025 Mar 12;6:1532885. doi: 10.3389/fpain.2025.1532885. eCollection 2025.

  PMID: 40144515 BACKGROUND

• Salvo E, Saraithong P, Curtin JG, Janal MN, Ye Y. Reciprocal interactions between cancer and Schwann cells contribute to oral cancer progression and pain. Heliyon. 2019 Feb 15;5(2):e01223. doi: 10.1016/j.heliyon.2019.e01223. eCollection 2019 Feb.

  PMID: 30815600 BACKGROUND

• Goyal N, Skrdla P, Schroyer R, Kumar S, Fernando D, Oughton A, Norton N, Sprecher DL, Cheriyan J. Clinical Pharmacokinetics, Safety, and Tolerability of a Novel, First-in-Class TRPV4 Ion Channel Inhibitor, GSK2798745, in Healthy and Heart Failure Subjects. Am J Cardiovasc Drugs. 2019 Jun;19(3):335-342. doi: 10.1007/s40256-018-00320-6.

  PMID: 30637626 BACKGROUND

MeSH Terms

Conditions

Mouth Neoplasms; Carcinoma, Squamous Cell

Interventions

Pressure

Condition Hierarchy (Ancestors)

Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Mouth Diseases; Stomatognathic Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Squamous Cell

Intervention Hierarchy (Ancestors)

Mechanical Phenomena; Physical Phenomena

Study Officials

• Brian L Schmidt, DDS

  NYU College of Dentistry

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yatendra Mulpuri, PhD

CONTACT

424-230-4222; ym2891@nyu.edu

Mariana Bucovsky, MHA

CONTACT

212-998-9389; mb10357@nyu.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 11, 2025
• First Posted: July 31, 2025
• Study Start: September 1, 2025
• Primary Completion (Estimated): June 30, 2029
• Study Completion (Estimated): December 30, 2029
• Last Updated: November 21, 2025

Record last verified: 2025-11

Locations

US (1)