Funded Projects

The growing opioid use epidemic in the U.S. has been associated with a significant increase in the prevalence of pregnant opioid-dependent women and neonatal abstinence syndrome, which is associated with adverse health effects for the infant and with costly hospitalizations. Maintenance with sublingual (SL) buprenorphine (BUP) is efficacious for opioid use disorder but has disadvantages that may be heightened in pregnant women, including the potential for poor adherence, treatment dropout, and negative maternal/fetal effects associated with daily BUP peak-trough cycles. Extended release (XR) formulations may address some of these disadvantages. The primary objective of CTN-0080 is to evaluate the impact of treating opioid use disorder in pregnant women (n = 300) with BUP-XR, compared to BUP-SL, on maternal-infant outcomes. Other objectives include testing a conceptual model of the mechanisms by which BUP-XR may improve maternal-infant outcomes, relative to BUP-SL; determining the economic value of BUP-XR, compared with BUP-SL, to treat OUD in pregnant women; and evaluating the impact of BUP-XR, relative to BUP-SL, on neurodevelopment when the infant/child is approximately 12 and 24 months of age. Ultimately, this study will help in increasing access to treatment as well as provide quality care for pregnant/postpartum women.

The growing opioid use epidemic in the U.S. has been associated with a significant increase in the prevalence of pregnant opioid-dependent women and neonatal abstinence syndrome, which is associated with adverse health effects for the infant and with costly hospitalizations. Maintenance with sublingual (SL) buprenorphine (BUP) is efficacious for opioid use disorder but has disadvantages that may be heightened in pregnant women, including the potential for poor adherence, treatment dropout, and negative maternal/fetal effects associated with daily BUP peak-trough cycles. Extended release (XR) formulations may address some of these disadvantages. The primary objective of CTN-0080 is to evaluate the impact of treating opioid use disorder in pregnant women (n = 300) with BUP-XR, compared to BUP-SL, on maternal-infant outcomes. Other objectives include testing a conceptual model of the mechanisms by which BUP-XR may improve maternal-infant outcomes, relative to BUP-SL; determining the economic value of BUP-XR, compared with BUP-SL, to treat OUD in pregnant women; and evaluating the impact of BUP-XR, relative to BUP-SL, on neurodevelopment when the infant/child is approximately 12 and 24 months of age. Ultimately, this study will help in increasing access to treatment as well as provide quality care for pregnant/postpartum women.

The growing opioid use epidemic in the U.S. has been associated with a significant increase in the prevalence of pregnant opioid-dependent women and neonatal abstinence syndrome, which is associated with adverse health effects for the infant and with costly hospitalizations. Maintenance with sublingual (SL) buprenorphine (BUP) is efficacious for opioid use disorder but has disadvantages that may be heightened in pregnant women, including the potential for poor adherence, treatment dropout, and negative maternal/fetal effects associated with daily BUP peak-trough cycles. Extended release (XR) formulations may address some of these disadvantages. The primary objective of CTN-0080 is to evaluate the impact of treating opioid use disorder in pregnant women (n = 300) with BUP-XR, compared to BUP-SL, on maternal-infant outcomes. Other objectives include testing a conceptual model of the mechanisms by which BUP-XR may improve maternal-infant outcomes, relative to BUP-SL; determining the economic value of BUP-XR, compared with BUP-SL, to treat OUD in pregnant women; and evaluating the impact of BUP-XR, relative to BUP-SL, on neurodevelopment when the infant/child is approximately 12 and 24 months of age. Ultimately, this study will help in increasing access to treatment as well as provide quality care for pregnant/postpartum women.

Emergency department (ED)-initiated buprenorphine/naloxone (BUP) with referral for ongoing BUP is superior to referral alone in engaging patients with untreated opioid use disorder (OUD) in treatment at 30 days and is cost-effective. However, logistical barriers exist in translating research into practice. New BUP formulations such as the extended-release injectable BUP (CAM2038, XR-BUP) hold promise in addressing many of the barriers more effectively than sublingual buprenorphine (SL-BUP) by treating the patients’ symptoms for up to seven days. This study will recruit, train and provide resources to 30 ED sites throughout the U.S. using implementation facilitation strategies to address stigma and provide ED-initiated BUP for patients presenting with OUD who are not receiving medications for OUD. Once implementation is adequately achieved, the sites will conduct a randomized controlled trial (RCT) to compare the effectiveness of SL-BUP versus XR-BUP on ED patients’ engagement in formal addiction treatment seven days after their ED visit. In addition, in an ancillary component of the study, the use of XR-BUP will be assessed in ED patients with Clinical Opioid Withdrawal Scale (COWS) scores of

The growing opioid use epidemic in the U.S. has been associated with a significant increase in the prevalence of pregnant opioid-dependent women and neonatal abstinence syndrome, which is associated with adverse health effects for the infant and with costly hospitalizations. Maintenance with sublingual (SL) buprenorphine (BUP) is efficacious for opioid use disorder but has disadvantages that may be heightened in pregnant women, including the potential for poor adherence, treatment dropout, and negative maternal/fetal effects associated with daily BUP peak-trough cycles. Extended release (XR) formulations may address some of these disadvantages. The primary objective of CTN-0080 is to evaluate the impact of treating opioid use disorder in pregnant women (n = 300) with BUP-XR, compared to BUP-SL, on maternal-infant outcomes. Other objectives include testing a conceptual model of the mechanisms by which BUP-XR may improve maternal-infant outcomes, relative to BUP-SL; determining the economic value of BUP-XR, compared with BUP-SL, to treat OUD in pregnant women; and evaluating the impact of BUP-XR, relative to BUP-SL, on neurodevelopment when the infant/child is approximately 12 and 24 months of age. Ultimately, this study will help in increasing access to treatment as well as provide quality care for pregnant/postpartum women.

Hospital inpatient stays due to opioid-related health problems are a reachable moment for increasing access to treatment with medications for opioid use disorder (MOUD). Hospitalized patients with opioid use disorder (OUD) are at particularly high risk for morbidity, mortality, and high medical costs in the U.S. This study will substantially inform the care management of OUD in hospitalized patients. The project includes a comparative effectiveness research trial and an implementation research trial, which will lead to models of broad dissemination for treatment approaches to this largely unaddressed population. They will examine whether (1) in hospitals with addiction medicine consultation services, hospital-initiated extended-release buprenorphine (XR-BUP), compared with other OUD medications, results in increased engagement in treatment with MOUD following hospital discharge and (2) training hospitals without such consultation services on best practices for initiating MOUD using consultation service hubs improves medication uptake in hospitals and increased MOUD treatment engagement following discharge.

Emergency department (ED)-initiated buprenorphine/naloxone (BUP) with referral for ongoing BUP is superior to referral alone in engaging patients with untreated opioid use disorder (OUD) in treatment at 30 days and is cost-effective. However, logistical barriers exist in translating research into practice. New BUP formulations such as the extended-release injectable BUP (CAM2038, XR-BUP) hold promise in addressing many of the barriers more effectively than sublingual buprenorphine (SL-BUP) by treating the patients’ symptoms for up to seven days. This study will recruit, train and provide resources to 30 ED sites throughout the U.S. using implementation facilitation strategies to address stigma and provide ED-initiated BUP for patients presenting with OUD who are not receiving medications for OUD. Once implementation is adequately achieved, the sites will conduct a randomized controlled trial (RCT) to compare the effectiveness of SL-BUP versus XR-BUP on ED patients’ engagement in formal addiction treatment seven days after their ED visit. In addition, in an ancillary component of the study, the use of XR-BUP will be assessed in ED patients with Clinical Opioid Withdrawal Scale (COWS) scores of

Hospital inpatient stays due to opioid-related health problems are a reachable moment for increasing access to treatment with medications for opioid use disorder (MOUD). Hospitalized patients with opioid use disorder (OUD) are at particularly high risk for morbidity, mortality, and high medical costs in the U.S. This study will substantially inform the care management of OUD in hospitalized patients. The project includes a comparative effectiveness research trial and an implementation research trial, which will lead to models of broad dissemination for treatment approaches to this largely unaddressed population. They will examine whether (1) in hospitals with addiction medicine consultation services, hospital-initiated extended-release buprenorphine (XR-BUP), compared with other OUD medications, results in increased engagement in treatment with MOUD following hospital discharge and (2) training hospitals without such consultation services on best practices for initiating MOUD using consultation service hubs improves medication uptake in hospitals and increased MOUD treatment engagement following discharge.

People who use opioids in rural areas suffer worse health and less insurance coverage. The opioid problem in rural areas is of particular concern, as rural areas have higher overdose rates despite equivalent rates of OUD. This is because rural areas have a scant number of clinics and clinicians who provide medication treatment for OUD. Thus, people living in rural areas must travel long distances to access clinics that may or may not have expertise in providing treatment to patients with OUD. Telemedicine (TM) could efficiently increase capacity for delivery of buprenorphine in rural areas and may increase the number of patients receiving medication treatment and improve treatment retention and outcomes. While the development of medication treatments for opioid use disorder (MOUD) capacity in primary care settings with optimal/comprehensive services is desirable, the current opioid crisis with escalating overdose death rates in rural areas suggests a need to implement an efficient, cost-effective system of MOUD services that can be scaled up quickly. The use of a centralized and Medicare-covered TM vendor utilizing a developed methodology and established organizational infrastructure offers the great potential for a rapid rollout to increase access to MOUD and improve treatment retention in rural areas. This cluster randomized clinical trial with two phases will test expanded treatment access to improve retention on MOUD in highly affected rural areas. Phase I will include implementing telemedicine in a limited number of rural sites with varying levels of office-based opioid treatment (OBOT) to inform implementation strategies for the main trial, and Phase II will include evaluate comparative effectiveness between OBOT alone and OBOT + TM at 30 sites.

Very little research has been conducted on better understanding of phenotypic characterization of individuals with OUD (beyond DSM-5 diagnoses) and how these features predict illness severity, treatment retention or outcomes. The primary objective of the deep phenotyping study is to provide a comprehensive phenotypic characterization (e.g., domains of negative affect, reward salience, cognitive control, mental health) of a heterogeneous sample of individuals (n = 1,000) who currently meet one or more DSM-5 diagnostic criteria for OUD and are in treatment for OUD. In a subset of this sample (n = 100), the investigators conduct digital phenotyping to examine the utility of ecological momentary assessment (EMA), digital sensing and social media to predict retention, medication adherence and opioid use outcomes in patients receiving buprenorphine for OUD. It is anticipated that this foundational study will inform the feasibility and utility of such assessments that can be successfully embedded into imminent and future CTN and other OUD clinical trials.

The U.S. is in the midst of a devastating opioid epidemic. Since 1999, the number of overdose (OD) deaths involving opioids has quadrupled. These trends are magnified among American Indians/Alaska Natives (AI/ANs) compared to other racial/ethnic groups. AI/ANs are second only to Whites in the rate of OD mortality (8/100,000 versus 12/100,000 deaths, respectively). Medications for opioid use disorder (OUD; i.e., methadone, buprenorphine and naltrexone) are considered the most effective treatment, reducing mortality and increasing abstinence and retention. However, numerous barriers limit the uptake of medications for OUD in tribal communities and within urban treatment settings serving AI/AN individuals. This is a two-phase formative research study to develop and test an implementation intervention for programs to provide medications to treat OUD specifically with AI/AN consumers. The objective of Phase I (12 months) is to develop a culturally centered implementation intervention to integrate medications for opioid use disorder (MOUD) into health care/addiction specialty settings. The objective of Phase II (24 months) is to conduct a preliminary test of the implementation intervention at four sites serving AI/AN communities. Community-based participatory research (CBPR) methods will be used throughout both phases. This study will help with decreasing stigma and increase the utilization of MOUD in health care settings that serve AI/AN populations.

A persistent problem in the dissemination of medications for opioid use disorder (MOUD) is patient dropout, and matching patients to suitable medication early has the potential to minimize dropout. The overall objective of this secondary data analysis study is to develop and disseminate individual level risk prediction models using harmonized data collected from three multi-site clinical trials from the CTN, in order to predict specific clinical outcomes (e.g., dropout, relapse) for patients treated with MOUD, including methadone, buprenorphine or extended-release depot naltrexone. The relative importance of predictors in the best predictive models will be estimated, which may facilitate refinement of common data elements for future OUD studies. The comprehensive, harmonized database of treatment data created in this study can be used for future secondary data analysis studies and will provide a replicable data pipeline to process and validate OUD data in future protocols.

A persistent problem in the dissemination of medications for opioid use disorder (MOUD) is patient dropout, and matching patients to suitable medication early has the potential to minimize dropout. The overall objective of this secondary data analysis study is to develop and disseminate individual level risk prediction models using harmonized data collected from three multi-site clinical trials from the CTN, in order to predict specific clinical outcomes (e.g., dropout, relapse) for patients treated with MOUD, including methadone, buprenorphine or extended-release depot naltrexone. The relative importance of predictors in the best predictive models will be estimated, which may facilitate refinement of common data elements for future OUD studies. The comprehensive, harmonized database of treatment data created in this study can be used for future secondary data analysis studies and will provide a replicable data pipeline to process and validate OUD data in future protocols.