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

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.

Study Overview

• Status: Terminated
• Conditions: Addiction
• Intervention / Treatment: Drug: escitalopram; Drug: Moclobemide; Drug: Placebo - Cap

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.

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 70 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: medication pills 1: escitalopram 10mg; 10mg once daily, 8 weeks	Drug: escitalopram; antidepressant use for the betel-quid abstinence; Other Names: Lexapro
EXPERIMENTAL: medication pills 2: moclobemide 150mg; 150mg once daily, 8 weeks	Drug: Moclobemide; antidepressant use for the betel-quid abstinence; Other Names: yutac
EXPERIMENTAL: medication pills 3: Placebo - Cap; placebo once daily, 8 weeks	Drug: Placebo - Cap; Placebo - Cap

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

Collaborators and Investigators

• Sponsor: China Medical University Hospital
• Investigators: Study Director: Ko Ying-Chin, PHD, China Medical University Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 14, 2016
• Primary Completion (ACTUAL): January 31, 2018
• Study Completion (ACTUAL): January 31, 2018

Study Registration Dates

• First Submitted: July 25, 2016
• First Submitted That Met QC Criteria: January 4, 2017
• First Posted (ESTIMATE): January 5, 2017

Study Record Updates

• Last Update Posted (ACTUAL): July 24, 2019
• Last Update Submitted That Met QC Criteria: July 22, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: addiction; clinical trial; drug therapy; betel-quid
• Additional Relevant MeSH Terms: Compulsive Behavior; Impulsive Behavior; Behavior, Addictive; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Antidepressive Agents, Second-Generation; Monoamine Oxidase Inhibitors; Citalopram; Moclobemide
• Other Study ID Numbers: C103RE1059

Plan for Individual participant data (IPD)

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