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Allele-specific Expression of a Bitter Taste Receptor

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ClinicalTrials.gov Identifier: NCT02766959
Recruitment Status : Completed
First Posted : May 10, 2016
Last Update Posted : September 18, 2018
Sponsor:
Collaborators:
University of Pennsylvania
Corporal Michael J. Crescenz VA Medical Center
Information provided by (Responsible Party):
Monell Chemical Senses Center

Brief 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 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.

Condition or disease Intervention/treatment
Rhinosinusitis Other: Observational study

  Show Detailed Description

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Study Type : Observational
Actual Enrollment : 57 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Bitter Taste and Allele-specific Expression of the Human TAS2R38 Gene
Study Start Date : January 2016
Actual Primary Completion Date : August 2017
Actual Study Completion Date : August 2018

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
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.
Other: Observational study
AVI/AVI
Individuals homozygous for the non-taster allele of the TAS2R38 gene, AVI/AVI.



Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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).


Secondary Outcome Measures :
  1. Bitter taste perception as measured by a visual analog scale [ Time Frame: Approximately 6 weeks after subject enrollment ]
    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.

  2. 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 ]
    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.

  3. Taste papillae density [ Time Frame: Approximately 6 weeks after subject enrollment ]
    Papillae density will be assessed at participant's post-procedure follow-up appointment, on average 6 weeks after enrollment.


Biospecimen Retention:   Samples With DNA
In part one of the study, each subject will provide a saliva sample. DNA will be isolated, purified, and quantitated for alleles of TAS2R38, a bitter taste receptor gene. Based on the results of the genetic screen, 25 individuals with the heterozygous genotype will be invited to return for part two of the study. In part two of the study, subject will provide nasal epithelium and taste tissue in the form of fungiform papillae. One half of each set of tissue will be placed in saline on ice in preparation for cell culture and assessment of AHL-induced defensive responses, while the second half will be placed in RNA preservative for mRNA isolation.


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Ages Eligible for Study:   21 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
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.
Criteria

Inclusion Criteria:

  • Key inclusion criteria include age 21-50 years
  • English speaking, and plans to undergo a sinonasal procedure for reconstructive purposes or other reasons.

Exclusion Criteria:

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02766959


Locations
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United States, Pennsylvania
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Monell Chemical Senses Center
Philadelphia, Pennsylvania, United States, 19104
Philadelphia Veterans Affairs Medical Center
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Monell Chemical Senses Center
University of Pennsylvania
Corporal Michael J. Crescenz VA Medical Center
Investigators
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Principal Investigator: Danielle R. Reed, Ph.D. Monell Chemical Senses Center
Principal Investigator: Noam A. Cohen, M.D., Ph.D. Monell Chemical Senses Center, University of Pennsylvania

Publications:

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Responsible Party: Monell Chemical Senses Center
ClinicalTrials.gov Identifier: NCT02766959     History of Changes
Other Study ID Numbers: 823078
First Posted: May 10, 2016    Key Record Dates
Last Update Posted: September 18, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Monell Chemical Senses Center:
chronic rhinosinusitis
airway physiology
taste receptors
tas2r
epithelial biology
upper respiratory disease