Clinical trial NCT02942745: Testing the Effectiveness of a Betel Nut Cessation Program
Official title: NIH-NCI U54 University of Guam/Cancer Center of Hawaii Partnership Full Project II: The Betel Nut Intervention Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Betel Nut Chewer
Tobacco Cessation
Lead sponsor: University of Guam
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: University of Hawaii Cancer Research Center
First posted: 2016-10-24
Enrollment: 276
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Areca nut, also known as betel nut, is the fourth most commonly consumed psychoactive substance in the world, following only alcohol, nicotine, and caffeine in prevalence of consumption. Although betel nut is chewed by approximately 600 million people globally, its use is concentrated in South Asia, Southeast Asia, and some Pacific Islands. Betel nut has been classified as a Group 1 carcinogen by the International Agency for Research on Cancer. Despite the global significance and carcinogenicity of betel nut, there has been very little behavioral or psychological research about betel nut chewing, and there has been no systematic research on the topic of betel nut cessation interventions. The current intervention builds directly upon the National Institutes of Health - National Cancer Institute's U54 University of Guam/University of Hawaii Cancer Center Comprehensive Partnership to Advance Health Equity. Previous data collected through the partnership suggest that betel nut chewers, like smokers, generally want and intend to quit, but do not have specific plans of how or when they will quit. In addition, most betel nut chewers in the partnership's previous study already have tried to quit on one or more occasions. The findings suggest that betel nut chewers could benefit from cessation programs modeled after smoking cessation programs. During 2014, partnership investigators conducted a feasibility study of the betel nut cessation program. The program was well received and yielded surprisingly high rates of self-reported betel nut cessation.

Specific Aim 1. To test the efficacy of an intensive group-based betel nut cessation program.

Specific Aim 2. To quantitatively determine the efficacy of the group-based betel nut cessation intervention trial using bio-verification.

Detailed description: The general framework employed to guide the intervention is cognitive-behavioral therapy. The cognitive-behavioral therapy is goal-oriented and problem-focused. The goal of the intervention is to help betel nut chewers to quit chewing betel nut using structured sessions. The cognitive component addresses chewers' attitudes and beliefs about betel nut chewing. Preliminary data from a feasibility study revealed that most participants initially underestimated such negative health effects of betel nut. The behavioral component of the intervention aims to replace chewing-promoting behaviors with behaviors that are more conducive to quitting betel nut and staying quit, and preparing responses for social situations where pressure to chew is likely to occur.

The structure of the proposed betel nut cessation program is modeled after a specific group-based cognitive-behavioral smoking cessation program. The program was selected because it is a well-established and evidence-based group cessation program. The intervention will consist of a 22-day, five-session support and informational group program. Betel nut use will be evaluated via surveys and bio-verification at three points: at the initial group meeting, at the final group meeting, and six months following the final group meeting.

Group Intervention Format and Procedures

Five group sessions will be conducted over a period of 22 days per cohort. Group meetings will be approximately one hour in length and will be conducted by study investigators and staff. Surveys will be administered at the first and last group meetings, as well as six months after the last meeting. Surveys will be self-administered at the beginning of the intervention sessions. Confidentiality will be emphasized at all meetings, but especially so in the first session, and will be addressed specifically in the informed consent document. Participants will be reminded that participation is completely voluntary and that withdrawal without penalty is always an option. At most sessions, handouts will be provided and topical "homework" will be distributed.

Saliva Samples

Saliva samples (ca. 1-2 mL) for intervention condition participants will be collected at the same times as the three survey assessments (baseline, the final group intervention session, and the six-month follow-up). Saliva samples for control condition participants (also ca. 1-2 mL) will be collected on the same schedule as the intervention condition participants. From the saliva samples, Dr. Adrian Franke's laboratory will measure by liquid chromatography mass spectrometry levels of salivary biomarkers previously identified in the pilot study, which identified compounds specific for areca nuts and betel leaves that were extracted while chewing three different betel preparations. The studies also revealed that the compounds are secreted into saliva and appear in chewers' saliva up to eight hours after the chewing event. To verify self-reports of betel nut abstinence, the investigators will set cut-offs for levels of alkaloids specific for areca nuts as follows: arecoline 60 ng/mL, arecaidine 10 ng/mL, guvacoline 20 ng/mL, and guvacine 6 ng/mL). Levels above the values will indicate evidence of recent betel nut consumption. Participants whose saliva tests reveal values above the specified cut-offs will be considered current chewers for the purposes of bio-verified outcomes (i.e., chewer or non-chewer status). The biomarker results will be used to compare self-reports of recent chewing behavior (amount and recency) with biomarker data to assess dose-response effects.

Saliva samples will be collected in Guam and Saipan in 20 mL conical polypropylene tubes which will be initially stored at -20°C. Aggregated samples will be shipped to Hawaii via FedEx. Shipments will be performed whenever 50-60 samples are successfully collected. After arriving in Hawaii, samples will be stored in Dr. Adrian Franke's lab at -80°C until analysis. All samples available at Dr. Adrian Franke's lab will be analyzed in one batch at the end of each annual cycle of the study.

Survey Assessments

Baseline Survey

The baseline survey will be administered during the first group session. Saliva samples will be collected.

First Follow-Up Survey

The first follow-up survey will be administered during the final group session. Participants will indicate any attempt to quit chewing betel nut since starting the intervention program, current chewing status (chewer or ex-chewer), number of group sessions attended (and reasons for absence, if applicable), and quid composition (if still chewing). The participants will also be asked several questions to measure satisfaction with the cessation program. Saliva samples will be collected for a second time.

Second Follow-Up Survey

Six months post-cessation, participants will arrange to meet with study staff to complete a final survey assessment. Participants will be asked again to evaluate the program, as well as follow-up questions regarding current chewing status and betel quid composition. Saliva samples will be collected for a final time.

Measurement of Cessation Outcomes

Primary cessation outcomes will be assessed by self-reported 7-day point prevalence abstinence bio-verified by the saliva tests. Participants who self-report chewing cessation but who test positive for the betel nut biomarker will be classified as chewers.

Data Analysis

The data analysis plan was designed under the direct guidance of the U54 Biostatistics Core. The goal of the analysis is to determine if the proposed intervention strategy affects cessation of betel nut chewing. Information on chewing behavior will be collected at baseline, month 1, and month 6 for the intervention (IN0, IN1, IN6) and control conditions (C0, C1, C6). The efficacy of the cessation program will be assessed by estimation and comparison of cessation prevalence over time, defined as the proportion who are not chewing betel nut. The first test of efficacy will compare the cessation status between randomization groups at month 1 and month 6, using a logistic mixed model, which will account for the repeated (correlated) measures within each individual. The independent variables will include randomization group (defined as intent-to- treat), time (parameterized as two indicator variables), location (Guam/Saipan), and interaction terms between group and time. Potential confounders, such as gender, ethnicity and age, will be added to the models. The F-test for the interaction term for 6 months will be the test of efficacy. Statistics of interest from the model include the odds ratio and 95% confidence interval (CI) comparing randomization groups, and the covariate-adjusted probabilities of cessation and their 95% CIs, predicted by group from the model. The data will be analyzed within subgroups, such as location (Guam or Saipan) to provide information on whether the intervention was more effective in select groups. The investigators will model treatment as the number of sessions attended to determine if the program was more effective in more compliant participants. The mixed model uses all available data points at each time point. If there is evidence of non-random missingness, such as by differential drop-out between groups, multiple imputation will be used to determine if missing data led to biased results.

Eligibility criteria: Inclusion Criteria:

* Self-described betel nut chewer (chewed betel nut for at least 1 year, and at a rate of at least 3 days per week). Must chew a quid consisting of areca nut, slaked lime, betel leaf, tobacco, and/or other optional ingredients.
* Age ≥ 18 years
* Reside in Guam or Saipan
* Able to understand, speak, and read English
* Provide signed informed consent and agree to comply with all protocol-specified procedures (e.g., providing saliva samples, participating in five one-hour group sessions over a period of 22 days) and follow-up evaluations

Exclusion Criteria:

* Chews betel nut without tobacco
* Does not speak, read, and/or write English
* Women who are pregnant or nursing
* Psychiatric illness/social situations that would limit compliance with study requirements
* Other illness that in the opinion of the investigator would exclude the patient from participating in this study

Primary outcomes:
measure: Change in number of participants who self-report that they quit chewing betel nut to be measured via survey
timeFrame: 22 days
measure: Change in number of participants who self-report that they quit chewing betel nut to be measured via survey
timeFrame: 6 months
Secondary outcomes:
measure: Levels of cotinine and betel nut biomarkers in saliva samples to be tested via liquid chromatography mass spectrometry
timeFrame: 22 days
measure: Levels of cotinine and betel nut biomarkers in saliva samples to be tested via liquid chromatography mass spectrometry
timeFrame: 6 months
Other outcomes:
Locations:
city: Mangilao Village
country: Guam
facility: University of Guam
Study officials:
affiliation: University of Guam, University of Hawaii
name: Yvette C Paulino, PhD, CPH
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Hawaii
name: Thaddeus A Herzog, PhD
role: PRINCIPAL_INVESTIGATOR
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