First-generation OTC Antihistamine Use and Voice Function: A Preliminary Study

The goal of this clinical trial is to learn about voice function before and 3 hours after administration of first generation over-the-counter antihistamine in individuals who have been medically diagnosed with allergies and routinely take over-the-counter (OTC) antihistamines for allergy symptoms. The main questions are:

1. Do first generation OTC antihistamines make voice function worse as measured via voice acoustic and aerodynamic measures? It is hypothesized that all objectives measures will reflect a negative change in voice function.
2. Do first generation OTC antihistamines make voice function worse as measured via participant and researcher perceptual measures? It is hypothesized that participants will rate their vocal function as more effortful after taking the antihistamine and researchers will rate voice quality as worse.

Participants ages 18-35 who have been diagnosed with allergies, are free of laryngeal pathology, and meet inclusion criteria will be consented. Participation in the study involves a pretrial visit and one day of data collection. The initial visit will obtain informed consent and train the trial measures. The 2nd day involves determination of systemic hydration (<1.02 g/ml), administration of the OTC antihistamine (Chlor-Trimeton), and measures taken at baseline and 3 hours after antihistamine administration. This antihistamine was selected for its lower sedation and anticholinergic effects than its other first-generation options. Each participant will take one, 12mg tablet. Onset action time for this antihistamine is 3 hours. Participants will be given water to consume during the 3 hour wait for the 2nd data time point to maintain hydration. Measures include routine clinical perceptual, acoustic, aerodynamic, and laryngeal imaging measures.

Study Overview

• Status: Completed
• Conditions: Voice Disorder Due to Iatrogenic Factor
• Intervention / Treatment: Drug: Chlor-Trimeton.

Detailed Description

Using a within-participant repeated measures design, ten 18-35-year-old males and females will be recruited locally to participate in this preliminary study. This age range was selected to assure laryngeal maturity following adolescence and avoid musculoskeletal/hormonal changes secondary to perimenopause. Informed consent will be obtained from each participant prior to screening for eligibility. Inclusion criteria: the ability to match pitch on a screening task, have diagnosed allergies of the upper airway, a Sino-nasal Outcome Test( SNOT-22) score of 20 or greater, pass videostroboscopic prescreening for laryngeal pathologies, no history of voice disorder, ability to comfortably breathe through both their nose and mouth, no history of drying medications other than the antihistamine, reflux, respiratory diseases, diabetes, neurological problems, hormone imbalance, pregnancy, breastfeeding over the preceding 6 months, or active smoker at the time of investigation. Participation in the study involves a pretrial visit and one day of data collection.

At the pretrial visit the participants will be screened for fever, cough, and other flu like symptoms using the screening questions outlined via Auburn's Human Research COVID-19 matrix. If a participant answers "yes" to any of the questions, the pretrial visit will be cancelled or postponed to a later day.

The pre-trial training visit will take place in the Auburn University Department of Speech, Language, and Hearing Sciences Voice Physiology Laboratory. If the participant passes the screener the pre-trial visit will include 1) the informed consent process, 2) collection of demographic data (age, sex, racial and ethnic identity, medications, time of day for medication intake), 3) the participant completing the SNOT-22, 4) completion of a routine laryngeal and vocal fold screening, and 5) training for the routine clinical acoustic and aerodynamic tasks. The laryngeal screening will be done by a trained speech-language pathologist in accordance with standard and routine laryngeal imaging procedures. Volunteers will be asked if they are allergic to topical Hurricaine spray. Volunteers unable to tolerate the procedure without application of topical anesthetic Hurricaine spray or allergic to Hurricaine spray will be thanked for their interest and dismissed from the study. Volunteers showing evidence of laryngeal pathology will be dismissed from the investigation and referred to their primary care provider.

The day prior to the trial visit the participants will be screened remotely via phone for fever, cough, and other flu like symptoms using the screening questions outlined via Auburn's Human Research COVID-19 matrix. If a participant answers "yes" to any of the questions, the trial visit will be cancelled and postponed to a later day. Participants will be reminded to wear a mask and/or face covering should that be required via application of the Auburn University COVID-19 matrix.

The trial visit will occur in Auburn University Speech and Hearing Clinic in the Voice Physiology Lab. Trial visits will be completed close to the same time of day across all participants to avoid variables associated with circadian rhythm.

1. A urine sample will be obtained for specific gravity analysis, a routine objective measurement of systemic hydration, via reagent strip for urinalysis (Siemens Multistix® 10 Specific Gravity Urine Test Strips, USA). A value of ≤ 1.020g/ml is a well-established threshold of appropriate systematic hydration. It is critical that adequate systemic hydration be established to ensure that the research variables of interest are due to the antihistamine drying effects. If a participant is not adequately hydrated, they will be asked to drink water until hydration criterion is achieved.
2. Participants will then complete a routine laryngeal and vocal fold screening. The laryngeal screening will be done in accordance with standard and routine laryngeal imaging procedures and will be completed by a speech-language pathologist who routinely conducts this procedure.
3. Participants will then complete the OMNI-Vocal Effort Scale (OMNI-VES) and the Rating-of-Fatigue Scale (ROF).
4. Acoustic parameters will then be collected using routine clinical measures within PRAAT (version 6.1.03), using a headset microphone placed 2 cm from the corner of the mouth. The participant will read standard sentences at conversational pitch and loudness and the following measures will be derived: speaking fundamental frequency and cepstral peak prominence (CPP). The participant will also be asked to sustain the vowel "a" at normal pitch and conversational loudness to determine the following: harmonic to noise ratio and mean fundamental frequency. All acoustic files will be saved under participant number and saved on a password protected share drive.
5. Aerodynamic measures will be collected using the PENTAX Phonatory Aerodynamic System (PAS) to assess phonation threshold pressure (PTP) using well-established standard routine clinical procedures. Aerodynamic measures are collected with a face mask and oral pressure tube that collect airflow and air pressure for a standard task.

After collecting the baseline measures for the participant, they will be administered the first-generation antihistamine, Chlor-Trimeton, at the recommended packaging dose, one, 12mg tablet. The onset of action time, the length of time it takes for the medication to start to work, for this antihistamine is 3 hours. During the 3 hours, the participant will be asked to sit and remain as quiet as possible. The participant is free to study or quietly use electronic during this period. The participant will also be instructed to drink a bottle of water to maintain their baseline hydration based on their age and sex. After the 3 hour time period has concluded, all perceptual, acoustic, aerodynamic, and laryngeal imaging measures will be completed again. This trial visit will take 4 hours. Total participant time will be approximately 5 hours for this study.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Auburn, Alabama, United States, 36849
      • Department of Speech, Language & Hearing Sciences, Auburn University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• the ability to match pitch on a screening task
• have diagnosed allergies of the upper airway
• a SNOT-22 score of 20 or greater (19)
• pass videostroboscopic prescreening for laryngeal pathologies
• no history of voice disorder
• ability to comfortably breathe through both their nose and mouth
• no history of drying medications other than the antihistamine, reflux, respiratory diseases, diabetes, neurological problems, hormone imbalance, pregnancy, breastfeeding over the preceding 6 months, or active smoker at the time of investigation.

Exclusion Criteria:

-

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Chlor-Trimeton; Package recommended dose of over the counter Chlor-Trimeton will be administered to assess voice function before and 3 hours after taking it.	Drug: Chlor-Trimeton.; Package dose of Chlor-Trimeton will be administered

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urine specific gravity (g/ml)	Objective measurement of systemic hydration	Start of trial
Fundamental frequency (Hertz)	Sustained "a" task from which the cycles of vocal fold vibration per second are extracted.	Change from Baseline Fundamental Frequency at 3 hours
Speaking fundamental frequency (Hertz)	Standard reading task from which the average cycles per second of vocal fold vibration are extracted.	Change from Baseline Fundamental Frequency at 3 hours
Harmonic-to-Noise ratio (decibels, dB)	Sustained "a" task from which a ratio of the harmonic acoustic components of the signal relative to the noise components of the acoustic signal are determined	Change from Baseline Fundamental Frequency at 3 hours
Cepstral peak prominence (decibels, dB)	An acoustic measurement of voice quality deviation that is extracted from a recorded speech sample.	Change from Baseline Fundamental Frequency at 3 hours
Phonation threshold pressure (cm/H20)	An aerodynamic measurement of the minimum amount of subglottal pressure required to initiate vocal fold vibration for voicing	Change from Baseline Fundamental Frequency at 3 hours
Videostroboscopy (video of vocal fold vibration)	Standard clinical endoscopic imaging of laryngeal structure and function	Change from Baseline Fundamental Frequency at 3 hours
OMNI-Vocal Effort Scale (scaled score)	A validated scale of perceived vocal effort that provides a scale of 1-10 from which to determine how much vocal effort was produced.	Change from Baseline Fundamental Frequency at 3 hours
Rating-of-Fatigue (ROF; scaled score)	A validated scale of perceived voice fatigue	Change from Baseline Fundamental Frequency at 3 hours

Collaborators and Investigators

• Sponsor: Auburn University
• Investigators: Principal Investigator: Mary J Sandage, PhD, Auburn University

Study record dates

Study Major Dates

• Study Start (Actual): June 13, 2023
• Primary Completion (Actual): April 15, 2024
• Study Completion (Actual): April 23, 2024

Study Registration Dates

• First Submitted: April 26, 2023
• First Submitted That Met QC Criteria: May 4, 2023
• First Posted (Actual): May 15, 2023

Study Record Updates

• Last Update Posted (Actual): April 24, 2024
• Last Update Submitted That Met QC Criteria: April 23, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Neurologic Manifestations; Otorhinolaryngologic Diseases; Laryngeal Diseases; Voice Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Dermatologic Agents; Anti-Allergic Agents; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Antipruritics; Chlorpheniramine
• Other Study ID Numbers: 23-175

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes