RhinosinusitisNCT02766959
Allele-specific Expression of a Bitter Taste Receptor
An observational study of Rhinosinusitis, run by Monell Chemical Senses Center at 3 sites in United States.
Trial summary
This single-site, within-subject experimental basic research study is designed to analyze the hypothesis that allele-specific expression of the bitter taste receptor T2R38 in taste tissue of individuals heterozygous for the taste receptor gene TAS2R38 correlates with that in nasal epithelium, and is responsible for… Read more about this study
- Who is it for?
- Ages 21 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Rhinosinusitis
- What is being tested?
- Observational study
- How many people
- 57 participants
- Where
- 3 sitesUnited States
- Study dates
- Jan 2016to Aug 2018
- Phase
- Observational
- 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 21 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Study population: One hundred subjects will be tested for TAS2R38 genotype. Our typical subject population is approximately 82% of European descent and 35% female. All subjects will be recruited from those seen in the department of otorhinolaryngology's rhinology division and planning to undergo a sinonasal procedure for reconstructive purposes. The initial interview will occur in the clinic setting. From these 100 subjects, 25 who are heterozygous for TAS2R38 will be asked to perform a taste test, complete a beverage frequency questionnaire, have their tongue photographed, and provide nasal epithelium and taste tissue during their procedure. Key exclusion criteria include a history of chronic rhinosinusitis, oral disease, and any condition that would prevent them from completing the psychophysical testing.
Who may be able to join
- English speaking, and plans to undergo a sinonasal procedure for reconstructive purposes or other reasons.
Who cannot join
- Key exclusion criteria include a history of chronic rhinosinusitis
- Plans to undergo a procedure for reasons other than reconstruction
- Oral disease
- Pregnancy, or any condition that would prevent psychophysical testing.
- Subjects showing signs of oral disease, including tongue lesions or xerostomia, would be excluded from tongue sampling, and therefore excluded from the study.
- Subjects will not be excluded because of economic status, gender, race or ethnicity.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Monell Chemical Senses Center
Philadelphia, Pennsylvania, 19104
Philadelphia Veterans Affairs Medical Center
Philadelphia, Pennsylvania, 19104
About this study
Official title: Bitter Taste and Allele-specific Expression of the Human TAS2R38 Gene
This single-site, within-subject experimental basic research study is designed to analyze the hypothesis that allele-specific expression of the bitter taste receptor T2R38 in taste tissue of individuals heterozygous for the taste receptor gene TAS2R38 correlates with that in nasal epithelium, and is responsible for differences in acyl-homoserine lactone-induced respiratory defenses. Subjects will include 100 predominantly European adults without chronic rhinosinusitis who will be undergoing a sinonasal procedure for reconstructive purposes. All subjects will provide saliva samples for genotyping, from which 25 subjects heterozygous for TAS2R38 (AVI/PAV) will be identified. These individuals will be asked to complete a beverage frequency questionnaire and taste test prior to the procedure that will evaluate for a number of compounds, among them bitter ligands specific to T2R38. Their tongue will also be photographed to evaluate the anatomy of their fungiform papillae, the mushroom-like structures on the tongue which contain taste buds. Subjects will subsequently provide nasal epithelium and taste tissue, which will be processed to 1) evaluate for allele-specific expression of TAS2R38 mRNA in both the taste and nasal tissue, with the nasal tissue concurrently being cultured in an air-liquid interface system to 2) assess the AHL-induced respiratory defenses of ciliary beat frequency (CBF) and nitric oxide (NO) production. Should subjects require a subsequent sinonasal procedure for clinically-determined reasons, taste and nasal tissue will again be obtained and analyzed for TAS2R38 mRNA, allowing for 3) longitudinal evaluation of mRNA expression level.
Read the detailed description
The Basic Biology of Bitter Taste. The perception of bitter taste is thought to have evolved as a mechanism to protect against the ingestion of toxic materials, and is the result of ligand-activation of one of more than 25 different bitter taste receptors, so-called T2Rs (1). These receptors are found on the tongue in what are called fungiform papillae, mushroom-like structures that contain taste buds with receptors responding to a variety of tastes including sweet, salty, sour, umami, and bitter. A prototypical example of one of these bitter ligands is phenylthiocarbamide (PTC), which actives the T2R38 receptor. While initially identified in type II taste cells, T2R38 is also expressed in nasal epithelium, where it participates in innate immune defense responses to invading bacteria (2-6).
TAS2R38: A Model System for Genotype-Phenotype Studies. Prior studies have identified two main forms of T2R38, active and inactive, which are characterized by three genetic variants in the TAS2R38 gene. These variants result in three amino acid changes, proline (P) to alanine (A) at position 49, alanine (A) to valine (V) at position 262, and valine (V) to isoleucine (I) at position 296 in the T2R38 receptor. Individuals who are homozygous for the active (PAV/PAV) form detect bitterness in compounds containing a thiourea (-N-C=S) moiety, including PTC, 6-n-propylthiouracil (PROP), and the plant compound goitrin, common in foods such as green vegetables (7-9). They also respond to acyl-homoserine lactones (AHLs), a class of compounds produced as signaling molecules by certain bacteria, triggering a rapid defense reaction consisting of increased ciliary beat frequency (CBF) to facilitate mucociliary clearance, and generation of nitric oxide (NO), a gas that can diffuse into the airway and kill bacteria (4). In contrast, those who are homozygous for all three variants (AVI/AVI) consume these compounds without perceiving them as bitter and do not appear to respond to AHLs (10). The frequency of both the active and inactive forms of TAS2R38 is at a near balance of 50:50 in many human racial groups, including Americans of European and African descent.
The Heterozygote Hypothesis. Interestingly, individuals heterozygous for the active form of the receptor (AVI/PAV) exhibit highly variable phenotypes, with some people very sensitive to bitter compounds, and others needing high concentrations to taste them at all (11). While the investigators know that taste papillae density plays at least some role in this variability
, our preliminary taste data suggest that the range of response is tied to how much mRNA is expressed from the active (PAV) form of the receptor, a concept called allele-specific expression (12). For example, this is the case when analyzing caffeine consumption, which strongly correlates with active mRNA expression (12). The investigators therefore hypothesize that the abundance of active TAS2R38 mRNA in heterozygous individuals also predicts the biologically significant change in magnitude of defensive responses in the presence of AHLs (13-15). The proposed study will determine whether this is in fact the case, and whether those people who have high mRNA abundance in taste tissue (fungiform papillae) also have correspondingly high abundance in nasal epithelium, or whether regulation is tissue-dependent. This will allow us to determine whether taste tests could provide a reliable representation of receptor function in other tissues and cell types. Should mRNA abundance prove to be a key factor, the investigators will determine whether high expressers sustain this expression over time.
Of note, a study performed by Dr. Reed and collaborators found that the population in Philadelphia contained 18% of individuals in the homozygous nontaster (AVI) group, 17% in the homozygous taster (PAV) group and 37% in the common heterozygous group (AVI/PAV) (16). The remaining 28% were distributed among ten other less common genotypes, which will not be analyzed in this study. Thus, as the majority of the population is heterozygous, a thorough understanding of their ability to fight infection is clinically important.
Clinical Significance. As one of the most common chronic conditions in the United States, chronic rhinosinusitis invokes a direct treatment cost of $3.5-5 billion annually. Its incidence is 146 per 1,000 and increasing (17). Our prior studies have shown that individuals with two copies of the active form of T2R38 have nasal epithelium that defends very effectively against certain bacteria, such as Pseudomonas aeruginosa, and are less likely to develop severe chronic rhinosinusitis requiring surgery, while those with two inactive forms cannot defend themselves as effectively, and are more likely to develop severe chronic rhinosinusitis requiring surgical intervention. Because the treatment of chronic rhinosinusitis involves multiple rounds of antibiotics and often surgical management through functional endoscopic sinus surgery (FESS), this research has significant implications for antibiotic stewardship, surgical morbidity and mortality, and health care expenditures.
- Conditions
- Rhinosinusitis
- Being tested
- Observational study
- Keywords
- chronic rhinosinusitis, airway physiology, taste receptors, tas2r, epithelial biology, upper respiratory disease
- Medical subject headings
- Rhinosinusitis, Respiration Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Observational studyOther
| Study group | Role | What they receive |
|---|---|---|
| PAV/PAV Tasters | Individuals homozygous for the taster allele of the TAS2R38 gene, PAV/PAV. | |
| AVI/PAV. | Individuals heterozygous for the taster allele of the TAS2R38 gene, AVI/PAV. Receives: Other: Observational study | |
| AVI/AVI | Individuals homozygous for the non-taster allele of the TAS2R38 gene, AVI/AVI. |
What is being measured
The primary outcome is the main question the study is designed to answer.
TAS2R38 genotype
A participant's genotype will be identified on enrollment in the study, the results of which could take up to 1 month to be performed.
Measured: Up to 1 month after enrollment.
TAS2R38 mRNA expression levels measured by RT-qPCR
Measured approximately 6 weeks after enrollment, based on the date of the participant's procedure.
Measured: Approximately 6 weeks after subject enrollment
Ciliary beat frequency
Measured approximately 6 weeks after enrollment, based on the date of the participant's procedure.
Measured: Approximately 6 weeks after subject enrollment
Production of nitric oxide by a participant's nasal epithelium culture measured in fold change of 4,5-diaminofluorescence diacetate
The production of nitric oxide (NO) by a patient's nasal epithelium culture will be measured approximately 6 weeks after enrollment, based on the date of his or her procedure. This will be measured by quantifying the fold change in fluorescence by using the NO-sensitive marker 4,5-diaminofluorescence diacetate (DAF-2).
Measured: Approximately 6 weeks after subject enrollment
Secondary outcomes (3)
Bitter taste perception as measured by a visual analog scale
Psychophysical bitter taste perception will be assessed by asking participants to taste a solution and rate its bitterness on a visual analog scale ranging from no intensity at all to extremely intense. This will be assessed at participant's post-procedure follow-up appointment, on average 6 weeks after enrollment.
Measured: Approximately 6 weeks after subject enrollment
Caffeine intake measured by number caffeinated beverages consumed per week (normalized to 1 cup = 180 mg caffeine)
The scale will be normalized to 1 cup = 180 mg caffeine. This will be assessed at participant's post-procedure follow-up appointment, on average 6 weeks after enrollment.
Measured: Approximately 6 weeks after subject enrollment
Taste papillae density
Papillae density will be assessed at participant's post-procedure follow-up appointment, on average 6 weeks after enrollment.
Measured: Approximately 6 weeks after subject enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 May 2016 (estimated)
- Study startJan 2016
- Primary completionAug 2017
- Study completionAug 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (19)Papers the sponsor has linked to this study.
- Other trials for RhinosinusitisStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 57 participants (actual)
Sponsor and investigators
- Lead sponsor
- Monell Chemical Senses Center
- Sponsor type
- University, hospital or other
- Collaborators
- University of Pennsylvania, Corporal Michael J. Crescenz VA Medical Center
- Responsible party
- Sponsor
- Investigators
- Danielle R. Reed, Ph.D., Principal investigator, Monell Chemical Senses CenterNoam A. Cohen, M.D., Ph.D., Principal investigator, Monell Chemical Senses Center, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02766959
- Sponsor's protocol ID
- 823078
- Status last verified
- Jan 2018
- First submitted
- 5 May 2016
- Last updated
- 18 Sep 2018
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Drewnowski A, Gomez-Carneros C. Bitter taste, phytonutrients, and the consumer: a review. Am J Clin Nutr. 2000 Dec;72(6):1424-35. doi: 10.1093/ajcn/72.6.1424.
PubMed 11101467Adler E, Hoon MA, Mueller KL, Chandrashekar J, Ryba NJ, Zuker CS. A novel family of mammalian taste receptors. Cell. 2000 Mar 17;100(6):693-702. doi: 10.1016/s0092-8674(00)80705-9.
PubMed 10761934Chandrashekar J, Mueller KL, Hoon MA, Adler E, Feng L, Guo W, Zuker CS, Ryba NJ. T2Rs function as bitter taste receptors. Cell. 2000 Mar 17;100(6):703-11. doi: 10.1016/s0092-8674(00)80706-0.
PubMed 10761935Lee RJ, Xiong G, Kofonow JM, Chen B, Lysenko A, Jiang P, Abraham V, Doghramji L, Adappa ND, Palmer JN, Kennedy DW, Beauchamp GK, Doulias PT, Ischiropoulos H, Kreindler JL, Reed DR, Cohen NA. T2R38 taste receptor polymorphisms underlie susceptibility to upper respiratory infection. J Clin Invest. 2012 Nov;122(11):4145-59. doi: 10.1172/JCI64240. Epub 2012 Oct 8.
PubMed 23041624Lee RJ, Kofonow JM, Rosen PL, Siebert AP, Chen B, Doghramji L, Xiong G, Adappa ND, Palmer JN, Kennedy DW, Kreindler JL, Margolskee RF, Cohen NA. Bitter and sweet taste receptors regulate human upper respiratory innate immunity. J Clin Invest. 2014 Mar;124(3):1393-405. doi: 10.1172/JCI72094. Epub 2014 Feb 17.
PubMed 24531552Tizzano M, Gulbransen BD, Vandenbeuch A, Clapp TR, Herman JP, Sibhatu HM, Churchill ME, Silver WL, Kinnamon SC, Finger TE. Nasal chemosensory cells use bitter taste signaling to detect irritants and bacterial signals. Proc Natl Acad Sci U S A. 2010 Feb 16;107(7):3210-5. doi: 10.1073/pnas.0911934107. Epub 2010 Jan 26.
PubMed 20133764Mueller KL, Hoon MA, Erlenbach I, Chandrashekar J, Zuker CS, Ryba NJ. The receptors and coding logic for bitter taste. Nature. 2005 Mar 10;434(7030):225-9. doi: 10.1038/nature03352.
PubMed 15759003Bufe B, Breslin PA, Kuhn C, Reed DR, Tharp CD, Slack JP, Kim UK, Drayna D, Meyerhof W. The molecular basis of individual differences in phenylthiocarbamide and propylthiouracil bitterness perception. Curr Biol. 2005 Feb 22;15(4):322-7. doi: 10.1016/j.cub.2005.01.047.
PubMed 15723792Wooding S, Bufe B, Grassi C, Howard MT, Stone AC, Vazquez M, Dunn DM, Meyerhof W, Weiss RB, Bamshad MJ. Independent evolution of bitter-taste sensitivity in humans and chimpanzees. Nature. 2006 Apr 13;440(7086):930-4. doi: 10.1038/nature04655.
PubMed 16612383Kim UK, Jorgenson E, Coon H, Leppert M, Risch N, Drayna D. Positional cloning of the human quantitative trait locus underlying taste sensitivity to phenylthiocarbamide. Science. 2003 Feb 21;299(5610):1221-5. doi: 10.1126/science.1080190.
PubMed 12595690Mennella JA, Pepino MY, Duke FF, Reed DR. Psychophysical dissection of genotype effects on human bitter perception. Chem Senses. 2011 Jan;36(2):161-7. doi: 10.1093/chemse/bjq106. Epub 2010 Oct 27.
PubMed 20980355Lipchock SV, Mennella JA, Spielman AI, Reed DR. Human bitter perception correlates with bitter receptor messenger RNA expression in taste cells. Am J Clin Nutr. 2013 Oct;98(4):1136-43. doi: 10.3945/ajcn.113.066688. Epub 2013 Sep 11.
PubMed 24025627Bartoshuk LM, Duffy VB, Miller IJ. PTC/PROP tasting: anatomy, psychophysics, and sex effects. Physiol Behav. 1994 Dec;56(6):1165-71. doi: 10.1016/0031-9384(94)90361-1.
PubMed 7878086Delwiche JF, Buletic Z, Breslin PA. Relationship of papillae number to bitter intensity of quinine and PROP within and between individuals. Physiol Behav. 2001 Oct;74(3):329-37. doi: 10.1016/s0031-9384(01)00568-6.
PubMed 11714496Melis M, Atzori E, Cabras S, Zonza A, Calo C, Muroni P, Nieddu M, Padiglia A, Sogos V, Tepper BJ, Tomassini Barbarossa I. The gustin (CA6) gene polymorphism, rs2274333 (A/G), as a mechanistic link between PROP tasting and fungiform taste papilla density and maintenance. PLoS One. 2013 Sep 9;8(9):e74151. doi: 10.1371/journal.pone.0074151. eCollection 2013.
PubMed 24040192
Study at a glance
From the registry record, last updated by the sponsor on 18 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bitter Taste and Allele-specific Expression of the Human TAS2R38 Gene
- ClinicalTrials.gov ID
- NCT02766959
- Acronym / sponsor ID
- 823078
- Conditions
- Rhinosinusitis
- Keywords
- chronic rhinosinusitis, airway physiology, taste receptors, tas2r, epithelial biology, upper respiratory disease
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 57 participants (actual)
- Lead sponsor
- Monell Chemical Senses CenterUniversity, hospital or other
- Collaborators
- University of Pennsylvania, Corporal Michael J. Crescenz VA Medical Center
- Study start
- Jan 2016
- Primary completion
- Aug 2017 (actual)
- Study completion
- Aug 2018 (actual)
- First posted
- 10 May 2016 (estimated)
- 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.
This single-site, within-subject experimental basic research study is designed to analyze the hypothesis that allele-specific expression of the bitter taste receptor T2R38 in taste tissue of individuals heterozygous for the taste receptor gene TAS2R38 correlates with that in nasal epithelium, and is responsible for differences in acyl-homoserine lactone-induced respiratory defenses. Subjects will include 100 predominantly European adults without chronic rhinosinusitis who will be undergoing a sinonasal procedure for reconstructive purposes. All subjects will provide saliva samples for genotyping, from which 25 subjects heterozygous for TAS2R38 (AVI/PAV) will be identified. These individuals will be asked to complete a beverage frequency questionnaire and taste test prior to the procedure that will evaluate for a number of compounds, among them bitter ligands specific to T2R38. Their tongue will also be photographed to evaluate the anatomy of their fungiform papillae, the mushroom-like structures on the tongue which contain taste buds. Subjects will subsequently provide nasal epithelium and taste tissue, which will be processed to 1) evaluate for allele-specific expression of TAS2R38 mRNA in both the taste and nasal tissue, with the nasal tissue concurrently being cultured in an air-liquid interface system to 2) assess the AHL-induced respiratory defenses of ciliary beat frequency (CBF) and nitric oxide (NO) production. Should subjects require a subsequent sinonasal procedure for clinically-determined reasons, taste and nasal tissue will again be obtained and analyzed for TAS2R38 mRNA, allowing for 3) longitudinal evaluation of mRNA expression level.
Detailed description
The Basic Biology of Bitter Taste. The perception of bitter taste is thought to have evolved as a mechanism to protect against the ingestion of toxic materials, and is the result of ligand-activation of one of more than 25 different bitter taste receptors, so-called T2Rs (1). These receptors are found on the tongue in what are called fungiform papillae, mushroom-like structures that contain taste buds with receptors responding to a variety of tastes including sweet, salty, sour, umami, and bitter. A prototypical example of one of these bitter ligands is phenylthiocarbamide (PTC), which actives the T2R38 receptor. While initially identified in type II taste cells, T2R38 is also expressed in nasal epithelium, where it participates in innate immune defense responses to invading bacteria (2-6).
TAS2R38: A Model System for Genotype-Phenotype Studies. Prior studies have identified two main forms of T2R38, active and inactive, which are characterized by three genetic variants in the TAS2R38 gene. These variants result in three amino acid changes, proline (P) to alanine (A) at position 49, alanine (A) to valine (V) at position 262, and valine (V) to isoleucine (I) at position 296 in the T2R38 receptor. Individuals who are homozygous for the active (PAV/PAV) form detect bitterness in compounds containing a thiourea (-N-C=S) moiety, including PTC, 6-n-propylthiouracil (PROP), and the plant compound goitrin, common in foods such as green vegetables (7-9). They also respond to acyl-homoserine lactones (AHLs), a class of compounds produced as signaling molecules by certain bacteria, triggering a rapid defense reaction consisting of increased ciliary beat frequency (CBF) to facilitate mucociliary clearance, and generation of nitric oxide (NO), a gas that can diffuse into the airway and kill bacteria (4). In contrast, those who are homozygous for all three variants (AVI/AVI) consume these compounds without perceiving them as bitter and do not appear to respond to AHLs (10). The frequency of both the active and inactive forms of TAS2R38 is at a near balance of 50:50 in many human racial groups, including Americans of European and African descent.
The Heterozygote Hypothesis. Interestingly, individuals heterozygous for the active form of the receptor (AVI/PAV) exhibit highly variable phenotypes, with some people very sensitive to bitter compounds, and others needing high concentrations to taste them at all (11). While the investigators know that taste papillae density plays at least some role in this variability
, our preliminary taste data suggest that the range of response is tied to how much mRNA is expressed from the active (PAV) form of the receptor, a concept called allele-specific expression (12). For example, this is the case when analyzing caffeine consumption, which strongly correlates with active mRNA expression (12). The investigators therefore hypothesize that the abundance of active TAS2R38 mRNA in heterozygous individuals also predicts the biologically significant change in magnitude of defensive responses in the presence of AHLs (13-15). The proposed study will determine whether this is in fact the case, and whether those people who have high mRNA abundance in taste tissue (fungiform papillae) also have correspondingly high abundance in nasal epithelium, or whether regulation is tissue-dependent. This will allow us to determine whether taste tests could provide a reliable representation of receptor function in other tissues and cell types. Should mRNA abundance prove to be a key factor, the investigators will determine whether high expressers sustain this expression over time.
Of note, a study performed by Dr. Reed and collaborators found that the population in Philadelphia contained 18% of individuals in the homozygous nontaster (AVI) group, 17% in the homozygous taster (PAV) group and 37% in the common heterozygous group (AVI/PAV) (16). The remaining 28% were distributed among ten other less common genotypes, which will not be analyzed in this study. Thus, as the majority of the population is heterozygous, a thorough understanding of their ability to fight infection is clinically important.
Clinical Significance. As one of the most common chronic conditions in the United States, chronic rhinosinusitis invokes a direct treatment cost of $3.5-5 billion annually. Its incidence is 146 per 1,000 and increasing (17). Our prior studies have shown that individuals with two copies of the active form of T2R38 have nasal epithelium that defends very effectively against certain bacteria, such as Pseudomonas aeruginosa, and are less likely to develop severe chronic rhinosinusitis requiring surgery, while those with two inactive forms cannot defend themselves as effectively, and are more likely to develop severe chronic rhinosinusitis requiring surgical intervention. Because the treatment of chronic rhinosinusitis involves multiple rounds of antibiotics and often surgical management through functional endoscopic sinus surgery (FESS), this research has significant implications for antibiotic stewardship, surgical morbidity and mortality, and health care expenditures.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| PAV/PAV Tasters | – | –Individuals homozygous for the taster allele of the TAS2R38 gene, PAV/PAV. |
| AVI/PAV. | – | Other: Observational studyIndividuals heterozygous for the taster allele of the TAS2R38 gene, AVI/PAV. |
| AVI/AVI | – | –Individuals homozygous for the non-taster allele of the TAS2R38 gene, AVI/AVI. |
Who may qualify
- Ages
- 21 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- One hundred subjects will be tested for TAS2R38 genotype. Our typical subject population is approximately 82% of European descent and 35% female. All subjects will be recruited from those seen in the department of otorhinolaryngology's rhinology division and planning to undergo a sinonasal procedure for reconstructive purposes. The initial interview will occur in the clinic setting. From these 100 subjects, 25 who are heterozygous for TAS2R38 will be asked to perform a taste test, complete a beverage frequency questionnaire, have their tongue photographed, and provide nasal epithelium and taste tissue during their procedure. Key exclusion criteria include a history of chronic rhinosinusitis, oral disease, and any condition that would prevent them from completing the psychophysical testing.
Key inclusion criteria (1 listed)
- English speaking, and plans to undergo a sinonasal procedure for reconstructive purposes or other reasons.
Key exclusion criteria (6 listed)
- Key exclusion criteria include a history of chronic rhinosinusitis
- Plans to undergo a procedure for reasons other than reconstruction
- Oral disease
- Pregnancy, or any condition that would prevent psychophysical testing.
- Subjects showing signs of oral disease, including tongue lesions or xerostomia, would be excluded from tongue sampling, and therefore excluded from the study.
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 |
|---|---|---|
| Observational study | Other | AVI/PAV. |
Primary outcome
TAS2R38 genotype
Time frame: Up to 1 month after enrollment.
A participant's genotype will be identified on enrollment in the study, the results of which could take up to 1 month to be performed.
TAS2R38 mRNA expression levels measured by RT-qPCR
Time frame: Approximately 6 weeks after subject enrollment
Measured approximately 6 weeks after enrollment, based on the date of the participant's procedure.
Ciliary beat frequency
Time frame: Approximately 6 weeks after subject enrollment
Measured approximately 6 weeks after enrollment, based on the date of the participant's procedure.
Production of nitric oxide by a participant's nasal epithelium culture measured in fold change of 4,5-diaminofluorescence diacetate
Time frame: Approximately 6 weeks after subject enrollment
The production of nitric oxide (NO) by a patient's nasal epithelium culture will be measured approximately 6 weeks after enrollment, based on the date of his or her procedure. This will be measured by quantifying the fold change in fluorescence by using the NO-sensitive marker 4,5-diaminofluorescence diacetate (DAF-2).
3 secondary outcomes
Bitter taste perception as measured by a visual analog scale
Time frame: Approximately 6 weeks after subject enrollment
Caffeine intake measured by number caffeinated beverages consumed per week (normalized to 1 cup = 180 mg caffeine)
Time frame: Approximately 6 weeks after subject enrollment
Taste papillae density
Time frame: Approximately 6 weeks after subject enrollment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2018.
- Background: PubMed 11101467Drewnowski A, Gomez-Carneros C. Bitter taste, phytonutrients, and the consumer: a review. Am J Clin Nutr. 2000 Dec;72(6):1424-35. doi: 10.1093/ajcn/72.6.1424.
- Background: PubMed 10761934Adler E, Hoon MA, Mueller KL, Chandrashekar J, Ryba NJ, Zuker CS. A novel family of mammalian taste receptors. Cell. 2000 Mar 17;100(6):693-702. doi: 10.1016/s0092-8674(00)80705-9.
- Background: PubMed 10761935Chandrashekar J, Mueller KL, Hoon MA, Adler E, Feng L, Guo W, Zuker CS, Ryba NJ. T2Rs function as bitter taste receptors. Cell. 2000 Mar 17;100(6):703-11. doi: 10.1016/s0092-8674(00)80706-0.
- Background: PubMed 23041624Lee RJ, Xiong G, Kofonow JM, Chen B, Lysenko A, Jiang P, Abraham V, Doghramji L, Adappa ND, Palmer JN, Kennedy DW, Beauchamp GK, Doulias PT, Ischiropoulos H, Kreindler JL, Reed DR, Cohen NA. T2R38 taste receptor polymorphisms underlie susceptibility to upper respiratory infection. J Clin Invest. 2012 Nov;122(11):4145-59. doi: 10.1172/JCI64240. Epub 2012 Oct 8.
- Background: PubMed 24531552Lee RJ, Kofonow JM, Rosen PL, Siebert AP, Chen B, Doghramji L, Xiong G, Adappa ND, Palmer JN, Kennedy DW, Kreindler JL, Margolskee RF, Cohen NA. Bitter and sweet taste receptors regulate human upper respiratory innate immunity. J Clin Invest. 2014 Mar;124(3):1393-405. doi: 10.1172/JCI72094. Epub 2014 Feb 17.
- Background: PubMed 20133764Tizzano M, Gulbransen BD, Vandenbeuch A, Clapp TR, Herman JP, Sibhatu HM, Churchill ME, Silver WL, Kinnamon SC, Finger TE. Nasal chemosensory cells use bitter taste signaling to detect irritants and bacterial signals. Proc Natl Acad Sci U S A. 2010 Feb 16;107(7):3210-5. doi: 10.1073/pnas.0911934107. Epub 2010 Jan 26.
- Background: PubMed 15759003Mueller KL, Hoon MA, Erlenbach I, Chandrashekar J, Zuker CS, Ryba NJ. The receptors and coding logic for bitter taste. Nature. 2005 Mar 10;434(7030):225-9. doi: 10.1038/nature03352.
- Background: PubMed 15723792Bufe B, Breslin PA, Kuhn C, Reed DR, Tharp CD, Slack JP, Kim UK, Drayna D, Meyerhof W. The molecular basis of individual differences in phenylthiocarbamide and propylthiouracil bitterness perception. Curr Biol. 2005 Feb 22;15(4):322-7. doi: 10.1016/j.cub.2005.01.047.
- Background: PubMed 16612383Wooding S, Bufe B, Grassi C, Howard MT, Stone AC, Vazquez M, Dunn DM, Meyerhof W, Weiss RB, Bamshad MJ. Independent evolution of bitter-taste sensitivity in humans and chimpanzees. Nature. 2006 Apr 13;440(7086):930-4. doi: 10.1038/nature04655.
- Background: PubMed 12595690Kim UK, Jorgenson E, Coon H, Leppert M, Risch N, Drayna D. Positional cloning of the human quantitative trait locus underlying taste sensitivity to phenylthiocarbamide. Science. 2003 Feb 21;299(5610):1221-5. doi: 10.1126/science.1080190.
- Background: PubMed 20980355Mennella JA, Pepino MY, Duke FF, Reed DR. Psychophysical dissection of genotype effects on human bitter perception. Chem Senses. 2011 Jan;36(2):161-7. doi: 10.1093/chemse/bjq106. Epub 2010 Oct 27.
- Background: PubMed 24025627Lipchock SV, Mennella JA, Spielman AI, Reed DR. Human bitter perception correlates with bitter receptor messenger RNA expression in taste cells. Am J Clin Nutr. 2013 Oct;98(4):1136-43. doi: 10.3945/ajcn.113.066688. Epub 2013 Sep 11.
- Individual participant dataSharing planned: No
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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.
Danielle R. Reed, Ph.D. principal investigator
Monell Chemical Senses Center
Noam A. Cohen, M.D., Ph.D. principal investigator
Monell Chemical Senses Center, University of Pennsylvania
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Rhinosinusitis, run by Monell Chemical Senses Center at 3 sites 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 1 inclusion and 6 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: finished, as of the sponsor's last update on 18 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
TAS2R38 genotype (time frame: Up to 1 month after enrollment.). The study lists 4 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 NCT02766959, which also lists 19 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 18 Sep 2018.