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

• ClinicalTrials.gov Identifier: NCT06017895
• Recruitment Status: Recruiting
• First Posted: August 30, 2023
• Last Update Posted: November 21, 2023
• Sponsor: Nanfang Hospital, Southern Medical University
• Information provided by (Responsible Party): Nanfang Hospital, Southern Medical University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Swallowing-induced Pain	Drug: doxepin solution; Other: Placebo	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 178 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Supportive Care
• Official Title: 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
• Actual Study Start Date: November 1, 2023
• Estimated Primary Completion Date: August 30, 2024
• Estimated Study Completion Date: September 15, 2024

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Redution of swallowing-induced pain [ Time Frame: Baseline, and 10, 20, 30, 60 minutes after administration ]
   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.

Secondary Outcome Measures :

1. Total Drowsiness Increase [ Time Frame: Baseline, and 10, 20, 30, 60 minutes after administration ]
   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.
2. Total Taste of the Agent [ Time Frame: 10, 20, 30 and 60 minutes after administration ]
   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.
3. Total Stinging or Burning From the Agent [ Time Frame: 10, 20, 30 and 60 minutes after administration ]
   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.
4. Difficulty in Swallowing Different Food [ Time Frame: Baseline, and 10, 20, 30, 60 minutes after administration ]
   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.
5. Patient Preference for Continuing Therapy With the Agent [ Time Frame: 60 minutes after administration ]
   Patients were asked if they would like to continue treatment with that particular agent at 60 minutes after assigned administration.
6. Adverse Event Profiles [ Time Frame: up to one day after administration ]
   Adverse events were assessed and record using the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Contacts

Contact: Jian Guan, Ph.D.; +86-13632102247; 51643930@qq.com

Locations

China, Guangdong

Southern medical university; Recruiting

Guangzhou, Guangdong, China, 510515

Contact: Jian Guan, Ph.D. 86+13632102247 guanjian5461@163.com

Principal Investigator: Jian Guan, Ph.D.

Sponsors and Collaborators

Nanfang Hospital, Southern Medical University

Investigators

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

More Information

• Responsible Party: Nanfang Hospital, Southern Medical University
• ClinicalTrials.gov Identifier: NCT06017895
• Other Study ID Numbers: NFEC-2023-351
• First Posted: August 30, 2023
• Last Update Posted: November 21, 2023
• Last Verified: November 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Nanfang Hospital, Southern Medical University:

Nasopharyngeal carcinoma; Oral mucositis; Radiotherapy; Swallowing-induced pain; Doxepin

Additional relevant MeSH terms:

Carcinoma; Nasopharyngeal Carcinoma; Breakthrough Pain; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Nasopharyngeal Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Pain; Neurologic Manifestations; Doxepin; Sleep Aids, Pharmaceutical; Hypnotics and Sedatives; Central Nervous System Depressants; Physiological Effects of Drugs; Antidepressive Agents, Tricyclic; Antidepressive Agents; Psychotropic Drugs; Histamine Antagonists; Histamine Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action