Antitussive Effect of a Naturally Flavored Syrup Containing Diphenhydramine, Compared With Dextromethorphan and Placebo

Antitussive Effect of a Naturally Flavored, Multi-Component Syrup Containing Diphenhydramine, Compared With Dextromethorphan and Placebo

The purpose of this study is to evaluate the antitussive (cough-suppressing) effects of two liquid medications: a combination of diphenhydramine and phenylephrine in a naturally cocoa flavoring, and, dextromethorphan syrup, compared with placebo.

Study Overview

• Status: Completed
• Conditions: Cough Reflex Sensitivity
• Intervention / Treatment: Drug: diphenhydramine/phenylephrine/cocoa; dextromethorophan; placebo; Drug: diphenhydramine/phenylephrine/cocoa; placebo; dextromethorphan; Drug: dextromethorphan; diphenhydramine/phenylephrine/cocoa; placebo; Drug: dextromethorophan; placebo; diphenhydramine/phenylephrine/cocoa; Drug: placebo; diphenhydramine/phenylephrine/cocoa; dextromethorphan; Drug: placebo; dextromethorphan; diphenhydramine/phenylephrine/cocoa

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • Bronx, New York, United States, 10461
      • Einstein Division/Montefiore Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• healthy adult nonsmokers
• onset of acute, viral upper respiratory tract infection (common cold) within 72 hours of enrollment

Exclusion Criteria:

• smokers
• history of asthma or other respiratory disorders

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A, B, then C; Subjects received the following: Period 1: single oral dose of diphenhydramine 25 mg and phenylephrine 10 mg, in naturally-flavored cocoa syrup (treatment A). Period 2: dextromethorphan syrup 30 mg (treatment B); Period 3: placebo liquid, dextrose in water, 20 mL (treatment C). Intervention: capsaicin cough challenge testing 2 hours after study drug ingestion.Each dosing period separated by 1-2 day washout period.	Drug: diphenhydramine/phenylephrine/cocoa; dextromethorophan; placebo; diphenhydramine 25 mg and phenylephrine 10 mg; dextromethorphan 30 mg; placebo.; Drug: diphenhydramine/phenylephrine/cocoa; placebo; dextromethorphan; diphenhydramine 25 mg and phenylephrine 10 mg; placebo; dextromethorphan 30 mg.; Drug: dextromethorphan; diphenhydramine/phenylephrine/cocoa; placebo; dextromethorphan 30 mg; diphenhydramine 25 mg and phenylephrine 10 mg; placebo; Drug: dextromethorophan; placebo; diphenhydramine/phenylephrine/cocoa; dextromethorphan 30 mg; placebo; diphenhydramine 25 mg and phenylephrine 10 mg; Drug: placebo; diphenhydramine/phenylephrine/cocoa; dextromethorphan; placebo; diphenhydramine 25 mg and phenylephrine 10 mg; dextromethorphan 30 mg; Drug: placebo; dextromethorphan; diphenhydramine/phenylephrine/cocoa; placebo; dextromethorphan 30 mg; diphenhydramine 25 mg and phenylephrine 10 mg
Experimental: A, C, then B; Subjects received the following: Period 1: single oral doce of diphenhydramine 25 mg and phenylephrine 10 mg, in naturally-flavored cocoa syrup (treatment A); Period 2: placebo liquid, dextrose in watwer, 20 mL (treatment C); Period 3: dextromethorphan syrup 30 mg (treatment B). Intervention: capsaicin cough challenge testing 2 hours after study drug ingestion.Each dosing period separated by 1-2 day washout period.	Drug: diphenhydramine/phenylephrine/cocoa; dextromethorophan; placebo; diphenhydramine 25 mg and phenylephrine 10 mg; dextromethorphan 30 mg; placebo.; Drug: diphenhydramine/phenylephrine/cocoa; placebo; dextromethorphan; diphenhydramine 25 mg and phenylephrine 10 mg; placebo; dextromethorphan 30 mg.; Drug: dextromethorphan; diphenhydramine/phenylephrine/cocoa; placebo; dextromethorphan 30 mg; diphenhydramine 25 mg and phenylephrine 10 mg; placebo; Drug: dextromethorophan; placebo; diphenhydramine/phenylephrine/cocoa; dextromethorphan 30 mg; placebo; diphenhydramine 25 mg and phenylephrine 10 mg; Drug: placebo; diphenhydramine/phenylephrine/cocoa; dextromethorphan; placebo; diphenhydramine 25 mg and phenylephrine 10 mg; dextromethorphan 30 mg; Drug: placebo; dextromethorphan; diphenhydramine/phenylephrine/cocoa; placebo; dextromethorphan 30 mg; diphenhydramine 25 mg and phenylephrine 10 mg
Experimental: B, A, then C; Subjects received the following: Period 1: dextromethorphan syrup 30 mg (treatment B); Period 2: single dose of oral diphenhydramine 25 mg and phenylephrine 10 mg, in a naturally-flavored cocoa syrup (treatment A); Period 3: placebo liquid, dextrose in water, 20 mL (treatment C). Intervention: capsaicin cough challenge testing 2 hours after study drug ingestion. Each dosing period separated by 1-2 day washout period.	Drug: diphenhydramine/phenylephrine/cocoa; dextromethorophan; placebo; diphenhydramine 25 mg and phenylephrine 10 mg; dextromethorphan 30 mg; placebo.; Drug: diphenhydramine/phenylephrine/cocoa; placebo; dextromethorphan; diphenhydramine 25 mg and phenylephrine 10 mg; placebo; dextromethorphan 30 mg.; Drug: dextromethorphan; diphenhydramine/phenylephrine/cocoa; placebo; dextromethorphan 30 mg; diphenhydramine 25 mg and phenylephrine 10 mg; placebo; Drug: dextromethorophan; placebo; diphenhydramine/phenylephrine/cocoa; dextromethorphan 30 mg; placebo; diphenhydramine 25 mg and phenylephrine 10 mg; Drug: placebo; diphenhydramine/phenylephrine/cocoa; dextromethorphan; placebo; diphenhydramine 25 mg and phenylephrine 10 mg; dextromethorphan 30 mg; Drug: placebo; dextromethorphan; diphenhydramine/phenylephrine/cocoa; placebo; dextromethorphan 30 mg; diphenhydramine 25 mg and phenylephrine 10 mg
Experimental: B, C, then A; Subjects received the following: Period 1: dextromethorphan 30 mg syrup (treatment B); Period 2: placebo liquid, dextrose in water, 20 mL (treatment C); Period 3: single dose of oral diphenhydramine 25 mg and phenylephrine 10 mg in a naturally-flavored cocoa syrup (treatment A). Intervention: capsaicin cough challenge testing 2 hours after study drug ingestion. Each dosing period separated by 1-2 day washout period.	Drug: diphenhydramine/phenylephrine/cocoa; dextromethorophan; placebo; diphenhydramine 25 mg and phenylephrine 10 mg; dextromethorphan 30 mg; placebo.; Drug: diphenhydramine/phenylephrine/cocoa; placebo; dextromethorphan; diphenhydramine 25 mg and phenylephrine 10 mg; placebo; dextromethorphan 30 mg.; Drug: dextromethorphan; diphenhydramine/phenylephrine/cocoa; placebo; dextromethorphan 30 mg; diphenhydramine 25 mg and phenylephrine 10 mg; placebo; Drug: dextromethorophan; placebo; diphenhydramine/phenylephrine/cocoa; dextromethorphan 30 mg; placebo; diphenhydramine 25 mg and phenylephrine 10 mg; Drug: placebo; diphenhydramine/phenylephrine/cocoa; dextromethorphan; placebo; diphenhydramine 25 mg and phenylephrine 10 mg; dextromethorphan 30 mg; Drug: placebo; dextromethorphan; diphenhydramine/phenylephrine/cocoa; placebo; dextromethorphan 30 mg; diphenhydramine 25 mg and phenylephrine 10 mg
Experimental: C, A, then B; Subjects received the following: Period 1: placebo liquid, dextrose in water, 20 mL (treatment C); Period 2: a single oral dose of diphenhydramine 25 mg and phenylephrine 10 mg in a naturally-flavored cocoa syrup (treatment A); Period 3: dextromethorphan 30 mg syrup (treatment B). Intervention: capsaicin cough challenge testing 2 hours after study drug ingestion. Each dosing period separated by 1-2 day washout period.	Drug: diphenhydramine/phenylephrine/cocoa; dextromethorophan; placebo; diphenhydramine 25 mg and phenylephrine 10 mg; dextromethorphan 30 mg; placebo.; Drug: diphenhydramine/phenylephrine/cocoa; placebo; dextromethorphan; diphenhydramine 25 mg and phenylephrine 10 mg; placebo; dextromethorphan 30 mg.; Drug: dextromethorphan; diphenhydramine/phenylephrine/cocoa; placebo; dextromethorphan 30 mg; diphenhydramine 25 mg and phenylephrine 10 mg; placebo; Drug: dextromethorophan; placebo; diphenhydramine/phenylephrine/cocoa; dextromethorphan 30 mg; placebo; diphenhydramine 25 mg and phenylephrine 10 mg; Drug: placebo; diphenhydramine/phenylephrine/cocoa; dextromethorphan; placebo; diphenhydramine 25 mg and phenylephrine 10 mg; dextromethorphan 30 mg; Drug: placebo; dextromethorphan; diphenhydramine/phenylephrine/cocoa; placebo; dextromethorphan 30 mg; diphenhydramine 25 mg and phenylephrine 10 mg
Experimental: C, B, then A; Subjects received the following: Period 1: placebo liquid, dextrose in water, 20 mL (treatment C); Period 2: dextromethorphan 30 mg syrup (treatment B); Period 3: a single oral dose of diphenhydramine 25 mg and phenylephrine 10 mg in a naturally-flavored cocoa syrup (treatment A). Intervention: capsaicin cough challenge testing 2 hours after study drug ingestion. Each dosing period separated by 1-2 day washout period.	Drug: diphenhydramine/phenylephrine/cocoa; dextromethorophan; placebo; diphenhydramine 25 mg and phenylephrine 10 mg; dextromethorphan 30 mg; placebo.; Drug: diphenhydramine/phenylephrine/cocoa; placebo; dextromethorphan; diphenhydramine 25 mg and phenylephrine 10 mg; placebo; dextromethorphan 30 mg.; Drug: dextromethorphan; diphenhydramine/phenylephrine/cocoa; placebo; dextromethorphan 30 mg; diphenhydramine 25 mg and phenylephrine 10 mg; placebo; Drug: dextromethorophan; placebo; diphenhydramine/phenylephrine/cocoa; dextromethorphan 30 mg; placebo; diphenhydramine 25 mg and phenylephrine 10 mg; Drug: placebo; diphenhydramine/phenylephrine/cocoa; dextromethorphan; placebo; diphenhydramine 25 mg and phenylephrine 10 mg; dextromethorphan 30 mg; Drug: placebo; dextromethorphan; diphenhydramine/phenylephrine/cocoa; placebo; dextromethorphan 30 mg; diphenhydramine 25 mg and phenylephrine 10 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Cough Reflex Sensitivity to Capsaicin	increase in C5 (decrease in cough reflex sensitivity). Capsaicin cough challenge involves subjects breathing in incremental doubling concentrations of aerosolized capsaicin, 1 minute apart, until the concentration of capsaicin (micromolar) inducing 5 or more coughs (C5) is reached.	2 hours after study drug administration

Collaborators and Investigators

• Sponsor: Montefiore Medical Center

Publications and helpful links

General Publications

• Dicpinigaitis PV, Dhar S, Johnson A, Gayle Y, Brew J, Caparros-Wanderley W. Inhibition of cough reflex sensitivity by diphenhydramine during acute viral respiratory tract infection. Int J Clin Pharm. 2015 Jun;37(3):471-4. doi: 10.1007/s11096-015-0081-8. Epub 2015 Feb 12.

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): June 1, 2014

Study Registration Dates

• First Submitted: January 31, 2014
• First Submitted That Met QC Criteria: February 12, 2014
• First Posted (Estimate): February 14, 2014

Study Record Updates

• Last Update Posted (Actual): February 28, 2018
• Last Update Submitted That Met QC Criteria: February 26, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: diphenhydramine; placebo; cough; phenylephrine; dextromethorphan; capsaicin; cough reflex
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Cough; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Antiemetics; Gastrointestinal Agents; Protective Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Cardiotonic Agents; Dermatologic Agents; Hypnotics and Sedatives; Anesthetics, Local; Respiratory System Agents; Anti-Allergic Agents; Sleep Aids, Pharmaceutical; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Antipruritics; Antitussive Agents; Sympathomimetics; Vasoconstrictor Agents; Mydriatics; Nasal Decongestants; Adrenergic alpha-1 Receptor Agonists; Diphenhydramine; Promethazine; Dextromethorphan; Phenylephrine; Oxymetazoline
• Other Study ID Numbers: MMC-IRB-13-10-170