Vortioxetine in the Treatment of Depression Associated With Head and Neck Cancers Undergoing Radiotherapy

A Multicenter, Randomized, Double-blind, Controlled Clinical Trial of Votioxetine in the Treatment of Depression After Radiotherapy for Head and Neck Cancer

The purpose of this study is to evaluate the effects of vortioxetine, once daily (QD), on mood disorders and cognitive dysfunction in patients with head and neck cancers undergoing radiotherapy.

Study Overview

• Status: Recruiting
• Conditions: Radiation Injuries
• Intervention / Treatment: Drug: Vortioxetine 10 mg; Other: Placebo

Detailed Description

Head and neck cancer (HNC) is the fifth most common cancer in the world, especially in South China. The incidence of depression and anxiety in HNC patients after radiotherapy is as high as 12% - 45% due to appearance changes, decreased swallowing function, dry mouth, pain and other discomfort. At the same time, radiotherapy, as mainstay of therapy for HNC, also causes different degrees of damage to the brain around the tumor, leading to secondary cognitive dysfunction. Depression, anxiety and cognitive impairment seriously affect the quality of life of HNC patients after radiotherapy. Recent studies have found that votioxetine has multimodal pharmacodynamic activity, which can not only improve symptoms of depression, but also significantly improve the cognitive function of patients. In this study, investigators will discuss the therapeutic effect of vortioxetine on the depression after radiotherapy in HNC patients through a multi-center, randomized and double-blind comparative clinical trial.

• Study Type: Interventional
• Enrollment (Anticipated): 208
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Yamei Tang, M.D.; Phone Number: +86 13556001002; Email: yameitang@hotmail.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510120
      • Recruiting
      • Sun Yat-sen Memorial Hospital
      • Contact: Yamei Tang, M.D.; Phone Number: +86 13556001992; Email: yameitang@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• (1) Received radiation therapy due to head and neck cancer.
• (2) The patient have depression symptoms (PHQ-9 score ≥ 8) and meet the ICD-10 (version 2019) diagnostic criteria.
• (3) Age>/= 18 years and age</=65.
• (4) Estimated life expectancy ≥ 12 months.
• (5) Constant caregivers who well understand and have willingness to sign a written informed consent document.

Exclusion Criteria:

• (1) The researcher believe that the subjects have the tendency of suicide, self mutilation or the score of "suicide concept" in item 10 of MADRS was ≥5, or they had committed suicide, self mutilation within 6 months before enrollment;
• (2) History of depressive disorder before radiotherapy for head and neck tumors;
• (3) History of other serious mental disorders, such as generalized anxiety disorder, drug and alcohol abuse, etc;
• (4) History of central nervous diseases such as Alzheimer's disease, Parkinson's disease, Stroke, uncontrolled epilepsy, etc., which lead to emotional and cognitive impairment and other serious and uncontrolled systemic diseases (such as cardiopulmonary insufficiency, etc.);
• (5) Baseline Mini Mental State Examination (MMSE) score ≤ 23 points (University or above), MMSE ≤ 22 points (middle school), MMSE ≤ 20 points (primary school), MMSE ≤ 17 points (illiteracy);
• (6) The subject with brain metastasis;
• (7) Hematological examination of subject: White blood cell count < 3.5×10^9/L, Platelet count < 100×10^9/L, Hemoglobin < 110g/L, Abnormal range of coagulation function like fibrinogen < 1.5g/L, or other coagulation abnormalities with clinical significance；
• (8) Blood biochemical examination of patients: Total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT) > 2.0 x upper limit of normal value, Creatinine > 1.5x upper limit of normal value, Blood sodium < 130mmol/L;
• (9) The subject has a history of severe drug allergy or is known to be allergic to any excipient of the test drug;
• (10) The subjects who could not effectively complete the neuropsychological test during the follow-up.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: routine supportive psychotherapy and votioxetine; On the basis of general psychotherapy, cognitive behavior therapy and supportive psychotherapy, the patients were given votioxetine 10mg/tablet, one tablet each time, once a day, for 2 months.	Drug: Vortioxetine 10 mg; Vortioxetine will be used with a dosage of 10mg once a day, for 2 months.
Placebo Comparator: routine supportive psychotherapy and control; On the basis of general psychotherapy, cognitive behavior therapy and supportive psychotherapy, the patients were given placebo, one tablet each time, once a day, for 2 months.	Other: Placebo; Placebo will be used with a dosage of one tablet once a day for 2 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 8 in the MADRS Total Score	MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms with a total possible score range from 0 to 60. Higher scores indicate greater severity of symptoms.	Baseline to Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 8 in the Digit Symbol Substitution Test (DSST)	The DSST assesses relative contributions of speed, memory, executive function and visual scanning. Higher scores-correct number of symbols reflects greater objective cognitive functioning.	Baseline to Week 8
Change from baseline to 8 weeks in Rey Auditory Verbal Learning Test (RAVLT)	The purpose of the RAVLT is to assess verbal learning and memory. Specifically, it assesses immediate memory span, new learning, susceptibility to interference, and recognition memory.	Baseline to Week 8
Change From Baseline to Week 8 in the Trail Making Test (TMT-A)	TMT-A assesses cognitive processing speed and consists of 25 circles distributed over a sheet of paper. Lower scores represent better speed of processing.	Baseline to Week 8
Percentage of participants with MADRS response at week 8	MADRS response was defined as a ≥50% decrease in MADRS total score from baseline	Baseline to Week 8
Change from baseline to 8 weeks in the HAM-A (Hamilton Anxiety Rating Scale)	HAM-A is a widely used and well-validated tool for measuring the severity of a patient's anxiety, Higher scores indicate greater severity of symptoms.	Baseline to Week 8
Change in the quality of life	Change from baseline to 8 weeks and endpoint mean scores in FACT-H&N (the Functional Assessment of Cancer Therapy-Head and Neck) Scale，Higher scores indicate greater severity of symptoms.	Baseline to Week 8
Change From Baseline to Week 8 in CGI-S (the Clinical Global Impressions-Severity) Score	The CGI-S assesses the clinician's impression of the subject's current state of mental illness and consists of one question for the investigator: "Considering your total clinical experience with this particular population, how mentally ill is the patient at this time?" which is rated on a seven-point scale (1=normal, not ill at all; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill).	Baseline to Week 8
Dropouts due to adverse events	Number of participants who dropped out due to adverse events during the trial	Baseline to Week 8
Dropouts due to inefficacy	Number of participants who dropped out due to inefficacy during the trial	Baseline to Week 8

Collaborators and Investigators

• Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
• Collaborators: Sun Yat-sen University; Affiliated Cancer Hospital & Institute of Guangzhou Medical University; Brain Hospital Affiliated to Guangzhou Medical University
• Investigators: Principal Investigator: Yamei Tang, Sun Yat-sen Memorial Hospital，Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2020
• Primary Completion (Anticipated): October 10, 2023
• Study Completion (Anticipated): April 1, 2024

Study Registration Dates

• First Submitted: March 22, 2021
• First Submitted That Met QC Criteria: March 25, 2021
• First Posted (Actual): March 26, 2021

Study Record Updates

• Last Update Posted (Actual): March 26, 2021
• Last Update Submitted That Met QC Criteria: March 25, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Depression; Cognitive function; Head and Neck Cancers; Vortioxetine
• Additional Relevant MeSH Terms: Behavioral Symptoms; Neoplasms; Neoplasms by Site; Wounds and Injuries; Depression; Head and Neck Neoplasms; Radiation Injuries; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Tranquilizing Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Serotonin Antagonists; Anti-Anxiety Agents; Serotonin 5-HT3 Receptor Antagonists; Vortioxetine
• Other Study ID Numbers: 20200813

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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