Comparison of Vortioxetine Versus Other Antidepressants With Pregabalin Augmentation in Burning Mouth Syndrome

Sponsor

Federico II University (Other)

Overall Status

Recruiting

CT.gov ID

NCT06025474

Collaborator

(none)

203

Enrollment

Location

Arms

18.7

Anticipated Duration (Months)

10.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Background: The treatment of Burning Mouth Syndrome (BMS) presents a challenge in tailoring appropriate medication for individual patients. Antidepressants have demonstrated efficacy in alleviating symptoms in most cases; however, a subset of patients exhibit limited or no response to these treatments. The augmentation with pregabalin to conventional treatment has shown promising outcomes in relieving pain and improving quality of life in chronic pain conditions. This study aimed to compare the efficacy of vortioxetine with other antidepressants (SSRIs/SNRIs) in combination with pregabalin in a cohort of unresponsive BMS patients and to predict treatment response using clinical data.

Methods: A 52-week randomized, open-label, active-controlled study was conducted, enrolling 203 BMS patients previously treated with one antidepressant for 12 weeks and non-responder to the treatment. The study sample have included two groups: Group A (136) received vortioxetine, while Group B (67) received SSRIs/SNRIs. Pregabalin (75mg/day) was added to both groups, with a potential dosage increase to 150mg/day for inadequate responders after 12 weeks.

Treatment response was assessed by measuring reduction in VAS and SF-MPQ scores (>50 or 1-2) and HAM-A and HAM-D scores (>50% or ≤7) at 12, 24, 36 and 52 weeks. Classical logistic regression with a stepwise algorithm and Random Forest machine learning models were used to predict treatment response.

Condition or Disease	Intervention/Treatment	Phase
Burning Mouth Syndrome	Drug: Vortioxetine 20Mg Tab Drug: Paroxetine 20 Mg Oral Tablet Drug: Sertraline 50 MG Drug: Citalopram 20mg Drug: Escitalopram 10mg Drug: Duloxetine 60 MG Drug: Pregabalin 75mg	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

203 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Comparative Evaluation of Vortioxetine Versus Other Antidepressants With Pregabalin Augmentation in Treatment-resistant Burning Mouth Syndrome: a Prospective Longitudinal Clinical Trial With Treatment Response Prediction

Actual Study Start Date :

Jan 1, 2023

Anticipated Primary Completion Date :

Oct 30, 2023

Anticipated Study Completion Date :

Jul 24, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Vortioxetine+Pregabalin VO group(20mg)+ PGB (75mg) N= 136 Vortioxetine 20 mg, encapsulated tablets, orally, once daily, then pregabalin 75 mg, encapsulated tablets, orally, once daily. Pregabalin (75mg/day) was added, with a potential dosage increase to 150mg/day for inadequate responders after 12 weeks	Drug: Vortioxetine 20Mg Tab Encapsulated vortioxetine immediate release tablets, once daily Other Names: Brintellix Drug: Pregabalin 75mg Encapsulated pregabalin tablets, once daily
Active Comparator: Paroxetine+Pregabalin P group (20mg) + PGB (75mg); N= 10 Paroxetine 20 mg, encapsulated tablets, orally, once daily, then pregabalin 75 mg, encapsulated tablets, orally, once daily. Pregabalin (75mg/day) was added, with a potential dosage increase to 150mg/day for inadequate responders after 12 weeks	Drug: Paroxetine 20 Mg Oral Tablet Encapsulated paroxetine tablets, once daily Drug: Pregabalin 75mg Encapsulated pregabalin tablets, once daily
Active Comparator: Sertraline+Pregabalin S group (50mg) + PGB (75mg); N= 8 Sertraline 50 mg, encapsulated tablets, orally, once daily, then pregabalin 75 mg, encapsulated tablets, orally, once daily. Pregabalin (75mg/day) was added, with a potential dosage increase to 150mg/day for inadequate responders after 12 weeks	Drug: Sertraline 50 MG Encapsulated sertraline tablets, once daily Drug: Pregabalin 75mg Encapsulated pregabalin tablets, once daily
Active Comparator: Citalopram+Pregabalin C group (20mg)+ PGB (75mg) N= 8 Citalopram 20 mg, encapsulated tablets, orally, once daily, then pregabalin 75 mg, encapsulated tablets, orally, once daily. Pregabalin (75mg/day) was added, with a potential dosage increase to 150mg/day for inadequate responders after 12 weeks	Drug: Citalopram 20mg Encapsulated citalopram tablets, once daily Drug: Pregabalin 75mg Encapsulated pregabalin tablets, once daily
Active Comparator: Escitalopram+Pregabalin E group (10mg) + PGB (75mg); N= 8 Escitalopram 10 mg, encapsulated tablets, orally, once daily, then pregabalin 75 mg, encapsulated tablets, orally, once daily. Pregabalin (75mg/day) was added, with a potential dosage increase to 150mg/day for inadequate responders after 12 weeks	Drug: Escitalopram 10mg Encapsulated escitalopram tablets, once daily Drug: Pregabalin 75mg Encapsulated pregabalin tablets, once daily
Active Comparator: Duloxetine+Pregabalin D group (60mg)+ PGB (75mg) N= 33 Duloxetine 60 mg, encapsulated tablets, orally, once daily, then pregabalin 75 mg, encapsulated tablets, orally, once daily. Pregabalin (75mg/day) was added, with a potential dosage increase to 150mg/day for inadequate responders after 12 weeks	Drug: Duloxetine 60 MG Encapsulated duloxetine tablets, once daily Drug: Pregabalin 75mg Encapsulated pregabalin tablets, once daily

Outcome Measures

Primary Outcome Measures

Visual Analog Scale (VAS) [4 times evaluation: time 0: 0 week; time 1: 12 weeks; time 2: 24 weeks; time 3: 36 weeks; time 4: 52 weeks]
The Visual Analog Scale (VAS) (Hayes and Patterson, 1921) is a well-validated unidimensional instrument for the measure of pain intensity (Hawker et al., 2011). The score is determined by measuring the distance on the line between the "no pain" and the mark of a patient mark, providing a range of scores from 0 to 10 (0 = no oral symptoms and 10 = the worst imaginable discomfort).
Short-form McGill Pain Questionnaire (SF-MPQ) [4 times evaluation: time 0: 0 week; time 1: 12 weeks; time 2: 24 weeks; time 3: 36 weeks; time 4: 52 weeks]
the short form of the McGill Pain Questionnaire (SF-MPQ) is a measure of the quality of pain and is a multidimensional pain questionnaire, which measures the sensory, affective, and evaluative aspects of the perceived pain (Hawker et al., 2011). It comprises 15 items from the original MPQ, each scored from 0 (none) to 3 (severe). The SF-MPQ score is obtained by summing the item scores (range 0-45). There are no established critical cutoff points for the interpretation of the scores and, as for the MPQ, a higher score indicates the worse pain.

Secondary Outcome Measures

Hamilton rating scale for Depression (HAM-D) [4 times evaluation: time 0: 0 week; time 1: 12 weeks; time 2: 24 weeks; time 3: 36 weeks; time 4: 52 weeks]
The HAM-D is a clinician-administered depression assessment scale; it contains 21 items pertaining to the affective field. The scores can range from 0 to 54. A score > 7 indicates an impairment. The scores in the range of 7-17 indicate a mild depression, the scores between 18 and 24 indicate a moderate depression, and the scores >24 indicate a severe depression
Hamilton rating scale for Anxiety (HAM-A) [4 times evaluation: time 0: 0 week; time 1: 12 weeks; time 2: 24 weeks; time 3: 36 weeks; time 4: 52 weeks]
The HAM-A (Hamilton, 1959) is a clinician-administered anxiety assessment scale. It comprises 14 items to measure both psychic anxiety and somatic anxiety. Each item is scored on a scale of 0-4, a total score <17 indicates a mild severity, 18-24 mild to moderate, and 25-30 moderate to severe (Hamilton, 1967).
Pittsburgh Sleep Quality Index (PSQI) [4 times evaluation: time 0: 0 week; time 1: 12 weeks; time 2: 24 weeks; time 3: 36 weeks; time 4: 52 weeks]
The PSQI (Buysse et al., 1989) explores the quality of sleep over a 1-month time interval generating seven "component" scores (0-3): subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication and daytime dysfunction (Carpenter and Andrykowski, 1998). The total score is obtained by the sum of all the sub-scores and ranges between 0 and 21. A total score greater than five discriminates poor sleepers from good sleepers with a high sensitivity (90%-99%) and specificity (84%-87%) (Curcio et al., 2013).

Other Outcome Measures

Clinical Global Impression Scale - Improvement (CGI-I) and Severity (CGI-S) [3 times evaluation: time 1: 12 weeks; time 2: 24 weeks; time 3: 36 weeks; time 4: 52 weeks]
CGI-I scale assesses the participant's improvement (or worsening) as assessed by the clinician relative to Baseline on a 7-point scale: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. Clinical Global Impression Scale-Severity of Illness (CGI-S) score-by-week as fixed effects.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

patients with a confirmed diagnosis of BMS based on the International Classification of Orofacial Pain, 1st edition [International Classification of Orofacial Pain, 1st edition (ICOP) Cephalalgia, 2020]
patients of any race or gender; complaining of oral burning recurring daily for >2 h per day for >3 months;
normal blood test findings (including blood count, blood glucose levels, glycated hemoglobin, serum iron, ferritin and transferrin).
BMS patients previously treated with one antidepressant for 12 weeks and non-responder to the treatment

Exclusion Criteria:

the presence of any disease that could be recognized as a causative factor of BMS,
a history of a psychiatric disorder or a neurological or organic brain disorder,
a history of alcohol or substance abuse,
the presence of Obstructive Sleep Apnea Syndrome (OSAS)
uncontrolled hypertension, diabetes, HIV, narrow-angle glaucoma, or participants enrolled in other investigational studies.
participants requiring continued treatment with medications that adversely interact with the study medications (eg, quinolone antibiotics, warfarin, agents inhibiting serotonin reuptake) or with hereditary problems of fructose intolerance, glucose galactose malabsorption, or sucrose isomaltase insufficiency
pregnancy and lactation were exclusion criteria, and women of childbearing potential were required to receive a highly effective form of contraception.