Establishment of Cessation Therapy by Clinical Trials for Subjects With Betel-quid Dependence and Oral Pre-cancer

Study Overview
=================
Brief Summary
-----------------
No medication existed for BQ dependence. No clinical trials existed for the drug therapy. Previous study showed that BQ possessed the antidepressant effect via pathway of monoamine oxidase A (MAO-A). An animal model also found that the arecoline from BQ has a property as MAO-A inhibitor. Therefore, the investigators hypothesized that inhibition of the MAO-A or antidepressants might reduce the BQ addiction severity. The investigators will conduct the randomization and double blinded with placebo controlled study with 90 participants with BQ dependence from the Family Medicine and ear, nose, and throat (ENT) outpatient department (OPD). All participants shall agree the informed consent. The range of age is from 18 to 65 years old. The participants are diagnosed as BQ use disorder without other psychiatry co-morbidity, according to the Diagnostic and Statistical Manual (DSM)-V criteria. Those who have severe physical illness, psychiatric illness, and other substance use disorder except cigarettes are excluded. All participants receive the semi-structure interview by DSM-V, International Classification of Diseases (ICD)-10, and Mini International Neuropsychiatric Interview by the psychiatrist. Before the intervention, the participants will finish their basic data, daily amount of cigarettes, betel nut, medical history and psycho-social rating scales. Next, in addition to counseling, the investigators will continue or modify the optimal antidepressants based on the previous results. The investigators will evaluate their BQ use condition as what has been measured in the natural observation study of the first year. The investigators will check the outcome measurement by visual analog scale, betel quid withdrawal severity scale, Yale-Brown Obsessive-Compulsive (Y-BOCS) - betel quid (BQ) scale. The investigators also followed their hamilton depression scale; Beck depression index; and Beck anxiety index in the baseline, 2nd, 4th, 6th , and 8th week. The investigators also obtained the participants' gene type if the participants also agree for the prediction of oral cancers.

Detailed Description
-----------------
We'll conduct the betel-quid (BQ) dependence clinical trial since 2016. Eligible cases will be enrolled for the following 8 week double-blinded placebo controlled trial. The groups will be divided into three groups. Outcome measures include BQ use condition, addiction severity rating scale, emotional rating scale including Beck Anxiety Index (BAI), Beck Depression Index (BDI), Hamilton Depression Scales (HAMDs), and urine BQ metabolites.

Official Title
-----------------
Establishment of Cessation Therapy by Clinical Trials for Subjects With Betel-quid Dependence and Oral Pre-cancer

Conditions
-----------------
Addiction

Intervention / Treatment
-----------------
* Drug: escitalopram
* Drug: Moclobemide
* Drug: Placebo - Cap


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: DSM-V criteria suitable for betelnut use disorder No severe physical disorder No major psychiatric illness Chinese Speaker Exclusion Criteria: Severe physical disorder Major psychiatric illness Inability to understand the whole protocol

Ages Eligible for Study
-----------------
Minimum Age: 14 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

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: medication pills 1: escitalopram 10mg<br>10mg once daily, 8 weeks | Drug: escitalopram<br>* antidepressant use for the betel-quid abstinence<br>* Other names: Lexapro;|
| Experimental: medication pills 2: moclobemide 150mg<br>150mg once daily, 8 weeks | Drug: Moclobemide<br>* antidepressant use for the betel-quid abstinence<br>* Other names: yutac;|
| Experimental: medication pills 3: Placebo - Cap<br>placebo once daily, 8 weeks | Drug: Placebo - Cap<br>* Placebo - Cap<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| betelnut use severity rating scale for addiction severity of betelnut | The betelnut severity rating scale is a questionnaire rated by the psychiatrist or trained psychologist/nurse, containing 21 yes or no questions about betelnut use | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hamilton Depression Rating Scale for depression | for depression | 8 weeks | 
| Beck depression index, copyrighted in Chinese (The Psychological Cooperation, Harcourt Brace& Company) | self-rating for depression | 8 weeks | 
| Beck anxiety index, copyrighted in Chinese (The Psychological Cooperation, Harcourt Brace& Company) | self-rating for anxiety | 8 weeks | 
| betelnut use Yale-Brown Obsessive Compulsive Disorder-like Scale for the craving status | Yale-Brown Obsessive Compulsive Disorder-like Scale, translated in Chinese and betelnut use craving form, a questionnaires containing 10 questions rated by the psychiatrist or trained psychologist/nurse, severity from 0-4 | 8 weeks | 
| betelnut metabolites urinary analysis | arecoline, arecaidine, and N-methylnipecotic acid checked by liquid chromatography mass spectrometry (LC-MS) | 8 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
addiction, betel-quid, drug therapy, clinical trial