Doxepin Solution for Alleviation of Stubborn Breakthrough Pain Induced by Swallowing in Patients Receiving Radiotherapy for Nasopharyngeal Carcinoma

Doxepin Solution for Alleviation of Stubborn Breakthrough Pain Induced by Swallowing in Patient Receiving Radiotherapy for Nasopharyngeal Carcinoma: A Multicenter, Randomized, Controlled, Double-Blind Clinical Trial

The goal of this clinical trial is to explore the effectiveness and adverse reactions of doxepin solution spray for alleviation of stubborn breakthrough pain induced by swallowing in patients receiving radiotherapy for nasopharyngeal carcinoma.

Study Overview

• Status: Recruiting
• Conditions: Swallowing-induced Pain
• Intervention / Treatment: Drug: doxepin solution; Other: Placebo

Detailed Description

Patients with nasopharyngeal carcinoma receiving radical radiotherapy or chemoradiotherapy who developed oral mucositis and had a swallowing-induced pain score ≥ 4 were recruited and randomly assigned 1:1 to the experimental group and the control group.

Patients in the experimental group received a doxepin solution spray to the posterior pharyngeal wall 10 minutes before eating. At least 12 hours later, when the swallowing-induced pain score ≥4, a placebo spray was administered to the posterior pharyngeal wall 10 minutes before eating.

Patients in the control group received a placebo spray to the posterior pharyngeal wall 10 minutes before eating. At least 12 hours later, when the swallowing-induced pain score ≥4, a doxepin solution spray was administered to the posterior pharyngeal wall 10 minutes before eating.

The swallowing-induced pain and incidence of adverse events were assessed at 10 minutes, 20 minutes, 30 minutes, and 1 hour after medication using a patient-reported questionnaire, and safety evaluation was conducted 1 day after treatment.

• Study Type: Interventional
• Enrollment (Estimated): 178
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jian Guan, Ph.D.; Phone Number: +86-13632102247; Email: 51643930@qq.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Recruiting
      • Southern Medical University
      • Contact: Jian Guan, Ph.D.; Phone Number: 86+13632102247; Email: guanjian5461@163.com
      • Principal Investigator: Jian Guan, Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Provide informed written consent.
2. Age ≥ 18 years.
3. Histologically confirmed as nasopharyngeal carcinoma, and currently undergoing radical radiotherapy or chemoradiotherapy.
4. Physical examination demonstrating the presence of radiation-induced mucositis in the oral cavity and/or oropharynx.
5. At least 4 (out of 10) patient-reported swallowing-induced pain as measured by the numeric rating scale of pain.
6. Being able to complete the questionnaires independently or with assistance.
7. ECOG Performance Status 0, 1 or 2.

Exclusion Criteria:

1. Known allergy to doxepin, tricyclic antidepressants, or any known component of the drug formulation.
2. Use of a tricyclic antidepressant or monoamine oxidase inhibitor within 14 days prior to registration.
3. Current untreated or unhealed oral candidiasis or oral herpes simplex virus infection.
4. Untreated narrow angle glaucoma within 6 weeks prior to registration.
5. Untreated urinary retention within 6 weeks prior to registration.
6. Administration of cryotherapy to prevent oral mucositis within 6 weeks prior to registration.
7. Current serious heart disease or a recent history of myocardial infarction.
8. Current untreated or unresolved conditions like epilepsy, hyperthyroidism, hepatic dysfunction, delirium, and neutropenia.
9. Pregnant or lactating women.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: doxepin solution; Patients received a doxepin solution spray to the posterior pharyngeal wall 10 minutes before eating. At least 12 hours later, when the swallowing-induced pain score ≥4, a placebo spray was administered to the posterior pharyngeal wall 10 minutes before eating.	Drug: doxepin solution; 2.0 mL doxepin solution (5mg/mL) sprayed to the posterior pharyngeal wall
Placebo Comparator: placebo; Patients received a placebo spray to the posterior pharyngeal wall 10 minutes before eating. At least 12 hours later, when the swallowing-induced pain score ≥4, a doxepin solution spray was administered to the posterior pharyngeal wall 10 minutes before eating.	Other: Placebo; 2.0 mL placebo sprayed to the posterior pharyngeal wall

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Redution of swallowing-induced pain	The redution of swallowing-induced pain was measured by the numerical analogue scale of 0 to 10, with 0=no pain and 10=worst pain in the questionnaires taken at baseline, and 10, 20, 30, 60 minutes after assigned administration.	Baseline, and 10, 20, 30, 60 minutes after administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Drowsiness Increase	The total drowsiness increase was measured by the numerical analogue scale of 0 to 10, with 0=no drowsiness and 10=extreme drowsiness in the questionnaires taken at baseline, and 10, 20, 30, 60 minutes after assigned administration.	Baseline, and 10, 20, 30, 60 minutes after administration
Total Taste of the Agent	The total taste of the agent was measured by the numerical analogue scale of 0 to 10, with 0=acceptable and 10=terrible in the questionnaires taken at 10, 20, 30 and 60 minutes after assigned administration.	10, 20, 30 and 60 minutes after administration
Total Stinging or Burning From the Agent	The stinging or burning of the oral cavity/oropharynx was measured by the numerical analogue scale of 0 to 10, with 0=no stinging or burning and 10=worst stinging or burning in the questionnaires taken at 10, 20, 30 and 60 minutes after assigned administration.	10, 20, 30 and 60 minutes after administration
Difficulty in Swallowing Different Food	The difficulty in swallowing liquids, pureed food and solid food was measured respectively by the numerical analogue scale of 0 to 10, with 0=not at all and 10=very much in the questionnaires taken at 10, 20, 30 and 60 minutes after assigned administration.	Baseline, and 10, 20, 30, 60 minutes after administration
Patient Preference for Continuing Therapy With the Agent	Patients were asked if they would like to continue treatment with that particular agent at 60 minutes after assigned administration.	60 minutes after administration
Adverse Event Profiles	Adverse events were assessed and record using the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0.	up to one day after administration

Collaborators and Investigators

• Sponsor: Nanfang Hospital, Southern Medical University
• Investigators: Principal Investigator: Jian Guan, Ph.D., Nanfang Hospital, Southern Medical University

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2023
• Primary Completion (Estimated): August 30, 2024
• Study Completion (Estimated): September 15, 2024

Study Registration Dates

• First Submitted: August 24, 2023
• First Submitted That Met QC Criteria: August 24, 2023
• First Posted (Actual): August 30, 2023

Study Record Updates

• Last Update Posted (Estimated): November 21, 2023
• Last Update Submitted That Met QC Criteria: November 19, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Radiotherapy; Oral mucositis; Nasopharyngeal carcinoma; Doxepin; Swallowing-induced pain
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Pain; Neurologic Manifestations; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Nasopharyngeal Neoplasms; Carcinoma; Nasopharyngeal Carcinoma; Breakthrough Pain; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Psychotropic Drugs; Antidepressive Agents; Hypnotics and Sedatives; Antidepressive Agents, Tricyclic; Sleep Aids, Pharmaceutical; Histamine Antagonists; Histamine Agents; Doxepin
• Other Study ID Numbers: NFEC-2023-351

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: No
• Studies a U.S. FDA-regulated device product: No