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

Study Overview
=================
Brief Summary
-----------------
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.

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.

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

Conditions
-----------------
Radiation Injuries

Intervention / Treatment
-----------------
* Drug: Vortioxetine 10 mg
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: routine supportive psychotherapy and votioxetine<br>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<br>* Vortioxetine will be used with a dosage of 10mg once a day, for 2 months.<br>|
| Placebo Comparator: routine supportive psychotherapy and control<br>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<br>* Placebo will be used with a dosage of one tablet once a day for 2 months.<br>|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Vortioxetine, Depression, Cognitive function, Head and Neck Cancers