Clinical trial NCT06291337: Ibuprofen Inhibits Human Sweet Taste
Official title: Ibuprofen, a Phenylpropanoic Acid Nonsteroidal Anti-inflammatory Drug, Inhibits Human Sweet Taste and Glucose Detection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Treatment of Sweet Taste Receptors Without or With an Oral Rinse of Ibuprofen Solution in Healthy Participants
Treatment of Sweet Taste Receptors Without or With an Oral Rinse of Naproxen Solution in Healthy Participants
Lead sponsor: Rutgers, The State University of New Jersey
Sponsor class: OTHER
Collaborators: name: Monell Chemical Senses Center
First posted: 2024-03-04
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: We are testing individual sin a within subject control for their sweet taste ratings of sugars without and with oral rinses of ibuprofen and naproxen.
Primary purpose: BASIC_SCIENCE

Brief summary: The sweet taste receptor, TAS1R2-TAS1R3, is expressed both orally, where it signals sweet taste, and extraorally in the intestine and pancreas, where it may affect glucose absorption and metabolism. Recently, ibuprofen and naproxen have been identified to inhibit human T1R3 when heterologously expressed in cells. In the present study, the initial objective was to determine if ibuprofen and naproxen inhibit interactions of sugars with human sweet taste receptor under normal, physiological conditions. Ten healthy participants were asked to rate sweetness intensity for a range of sweet stimuli (sucrose, fructose, sucralose) after a prerinse of ibuprofen, naproxen or water. Both ibuprofen and naproxen inhibited sweet taste intensity in a dose-dependent manner. In association studies, ibuprofen use has been linked to preserved metabolic function, as its use is correlated with lower rates of Alzheimer's disease, diabetes and colon cancer. Here the investigators present a potential novel pathway for systemic ibuprofen to impact these metabolic diseases.

Detailed description: The sweet taste receptor, TAS1R2-TAS1R3, is expressed both orally, where it signals sweet taste, and extraorally in the intestine and pancreas, where it may affect glucose absorption and metabolism. Lactisole is a well characterized negative allosteric modulator of the transmembrane domain of T1R3. Lactisole binds with a phenylpropionic acid moiety. More recently, ibuprofen and naproxen, which are similar to lactisole in structure, have been identified to inhibit human T1R3 when heterologously expressed in cells. In the present study, the initial objective was to determine if ibuprofen and naproxen inhibit interactions of sugars with human sweet taste receptor under normal, physiological conditions. Ten healthy participants were asked to rate sweetness intensity for a range of sweet stimuli (sucrose, fructose, sucralose) after a prerinse of ibuprofen, naproxen or water. Both ibuprofen and naproxen inhibited sweet taste intensity in a dose-dependent manner. The experiment was repeated in vitro with TAS1R2-TAS1R3 expressing human cells, with ibuprofen reducing signaling of sucrose and sucralose. To explore ibuprofen's potential connection with glucose signaling and metabolism, the investigators next tested whether prerinses of lower concentrations of ibuprofen including a typical peak plasma concentrations (0.18 mM, 0.57 mM and 5.7 mM), would affect sweet taste intensity ratings of lower levels of glucose. Ibuprofen inhibited glucose sweetness in a dose dependent manner. Finally, the investigators tested whether prerinses of 0.12 mM and 0.24 mM ibuprofen (resulting from ingestion of two or three 200 mg pills respectively) affects detection thresholds of glucose, which are concentrations nearing post-prandial plasma glucose levels. Detection thresholds were significantly higher after rinsing with 0.24 mM ibuprofen compared to water rinses (p\<0.01, n=12). In association studies, ibuprofen use has been linked to preserved metabolic function, as its use is correlated with lower rates of Alzheimer's disease, diabetes and colon cancer. Here the investigators present a potential novel pathway for systemic ibuprofen to impact these metabolic diseases.

Eligibility criteria: Inclusion Criteria:

* Participant must be able to taste sugars as sweet
* Participant must be able to make ratings on a scale and follow instructions

Exclusion Criteria:

* Participant must not be on any medications that would preclude exposure to NSAIDS
* Participant must not be on any medications that are know to alter taste perception

Primary outcomes:
measure: Sweet taste ratings
timeFrame: 6 months
measure: Sugar detection thresholds
timeFrame: 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: New Brunswick
country: United States
facility: Food Science and Nutritional Sciences
state: New Jersey
Study officials:
affiliation: Rutgers University
name: Paul A Breslin, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: