Study protocol for a cluster randomized trial of a school, family, and community intervention for preventing drug misuse among older adolescents in the Cherokee Nation
Authors: Komro Kelli A. , Kominsky Terrence K. , Skinner Juli R. , Livingston Melvin D. , Livingston Bethany J. , Avance Kristin , Lincoln Ashley N. , Barry Caroline M. , Walker Andrew L. , Pettigrew Dallas W. , Merlo Lisa J. , Cooper Hannah L. F. , Wagenaar Alexander C. 
Published: February 2022

Abstract
Background
The national opioid crisis has disproportionately burdened rural White populations and American Indian/Alaska Native (AI/AN) populations. Therefore, Cherokee Nation and Emory University public health scientists have designed an opioid prevention trial to be conducted in rural communities in the Cherokee Nation (northeast Oklahoma) with AI and other (mostly White) adolescents and young adults. Our goal is to implement and evaluate a theory-based, integrated multi-level community intervention designed to prevent the onset and escalation of opioid and other drug misuse. Two distinct intervention approaches—community organizing, as implemented in our established Communities Mobilizing for Change and Action (CMCA) intervention protocol, and universal school-based brief intervention and referral, as implemented in our established Connect intervention protocol—will be integrated with skill-based training for adults to strengthen social support for youth and also with strategic media. Furthermore, we will test systems for sustained implementation within existing organizational structures of the Cherokee Nation and local schools and communities. This study protocol describes the cluster randomized trial, designed to measure implementation and evaluate the effectiveness on primary and secondary outcomes.

Methods
Using a cluster randomized controlled design and constrained randomization, this trial will allocate 20 high schools and surrounding communities to either an intervention or delayed-intervention comparison condition. With a proposed sample of 20 high schools, all enrolled 10th grade students in fall 2021 (ages 15 to 17) will be eligible for participation. During the trial, we will (1) implement interventions through the Cherokee Nation and measure implementation processes and fidelity, (2) measure opioid and other drug use and secondary outcomes every 6 months among a cohort of high school students followed over 3 years through their transition out of high school, (3) test via a cluster randomized trial the effect of the integrated CMCA-Connect intervention, and (4) analyze implementation costs. Primary outcomes include the number of days during the past 30 days of (1) any alcohol use, (2) heavy alcohol use (defined as having at least four, among young women, or five, among young men, standard alcoholic drinks within a couple of hours), (3) any marijuana use, and (4) prescription opioid misuse (defined as “without a doctor’s prescription or differently than how a doctor or medical provider told you to use it”).

Discussion
This trial will expand upon previous research advancing the scientific evidence regarding prevention of opioid and other drug misuse during the critical developmental period of late adolescent transition to young adulthood among a sample of American Indian and other youth living within the Cherokee Nation reservation.

Trial registration
ClinicalTrials.gov NCT04839978. Registered on April 9, 2021. Version 4, January 26, 2022