Funded Projects

NOFO Title: Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)
NOFO Number: PA-18-591
Summary:

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.

NOFO Title: Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)
NOFO Number: PA-18-591
Summary:

Effective treatment for OUD has been shown to improve patient outcomes and reduce health care costs; however, evidence of this effect in primary care settings is severely limited. The health economic findings from this study will supplement the parent PROUD trial’s results regarding clinical effectiveness and implementation outcomes and provide critical contextual information for health systems and other health care stakeholders. The study will evaluate the economic viability of the PROUD collaborative care model for OUD—that is, from the perspective of the health care sector, to what extent do the downstream cost savings associated with improved patient outcomes offset the additional costs of the PROUD intervention? The specific aims are to (1) estimate the start-up and ongoing management costs of the PROUD intervention, (2) assess costs associated with health care utilization for patients who receive primary care treatment in PROUD and usual care clinics and have been identified with recognized OUDs before clinic randomization, and (3) estimate the economic value of the PROUD intervention, measured as net monetary benefit (NMB, incremental benefit minus incremental cost), from the health care sector perspective.

NOFO Title: HEAL Initiative: Effectiveness Trials to Optimize, Implement, Scale, and Sustain the Collaborative Care Model for Individuals with Opioid Use Disorders and Mental Health Conditions (U01 Clinical Trial Required)
NOFO Number: RFA-MH-19-525
Summary:

Some medications for opioid use disorder (MOUD) can be provided in primary care (PC). Systems of team-based PC show promise for improving access and retention in OUD treatment. One such model, collaborative care (CC), includes a care manager, supervised by experts, who help provide evidence-based high-quality OUD care. While CC improves outcomes of depression, other mental health and substance use (MH/SU) disorders and pain, it is unknown how to optimally integrate CC for OUD with other MH/SU disorders. This pragmatic trial tests whether our model of CC for OUD and comorbid conditions increases engagement in MOUD treatment and improves depression symptoms in PC patients with OUD and depression. Innovative pragmatic elements include inclusion of all eligible patients in participating PC clinics, random recruitment and consent, and measurement of main outcomes using only secondary data. These pragmatic elements avoid studying only motivated patients and avoid activating patients randomized to usual care.

NOFO Title: PHS 2016-02 Omnibus Solicitation of the NIH, CDC, FDA, and ACF for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44])
NOFO Number: PA-16-302
Summary:

Since 2002, persons with opioid use disorders who desire medication-assisted treatment can be treated with buprenorphine, which has been shown to be efficacious. Buprenorphine treatment can occur in any medical office-based setting, is prescribed by any physician who seeks to become waivered, and is taken by patients at home unsupervised. However, without visual confirmation of medication ingestion, providers remain unsure if patients divert part or all of their buprenorphine medication. This project will develop the technical and logistical workflow needed to implement a video-­based application, miDOT, for office-­based buprenorphine monitoring during the initial months of care, which will allow health care providers to monitor whether patients ingest the drug and adhere to treatment. The project will configure a video-based DOT platform, evaluate its effectiveness in securing medication ingestion and care retention for illicit opiate users, and solidify routes of sustainable commercial viability with commercial partners.

NOFO Title: HEAL Initiative: America’s Startups and Small Businesses Build Technologies to Stop the Opioid Crisis (R43/R44 - Clinical Trial Optional)
NOFO Number: RFA-DA-19-019
Summary:

Chronic pain affects more than 100 million adults in the United States, resulting in disability, loss of work productivity, and overall reductions in health, making chronic pain a major public health problem with an economic burden estimated at $560–635 billion annually. Opioids, the most frequently prescribed class of drugs to control pain, lack evidence supporting their long-term efficacy and carry a 15% to 26% risk of misuse and abuse among pain patients. Guided imagery (GI) is an effective non-pharmacological intervention for reducing pain, but its effectiveness is limited by patients’ imaging abilities. This project will develop and assess the feasibility of an at-home virtual reality system, Limbix VR Kit, to reduce chronic pain and opioid reliance, as well as improve other functional outcomes, by delivering an immersive GI experience.

NOFO Title: HEAL Initiative: America’s Startups and Small Businesses Build Technologies to Stop the Opioid Crisis (R43/R44 - Clinical Trial Optional)
NOFO Number: RFA-DA-19-019
Summary:

Opioids have been found to be ineffective for chronic lower back pain (CLBP), yet they are still commonly prescribed. TAMADÉ, LLC aims to leverage a novel and validated technology based on virtual reality (VR) to provide therapy to CLBP patients on a daily opioid dosage with an opioid-sparing pain management tool aiming to increase pain management efficacy and decrease health complications. The intervention uses VR to stimulate patients’ visual, auditory, and haptic fields in order to simultaneously distract and actively engage patients in biofeedback therapy, where patients consciously self-regulate their nervous system by paring down their sympathetic tone through exercises in controlling respiration and heart rate. The study will compare patients receiving the proposed VR-based intervention with a group receiving either just opioids or opioids with sham VR. All groups will receive the same opioid tapering guidelines.

NOFO Title: PHS 2018-02 Omnibus Solicitation of the NIH, CDC, and FDA for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44] Clinical Trial Not Allowed)
NOFO Number: PA-18-574
Summary:

Newborn Abstinence Syndrome, which results from maternal opioid drug use prior to birth, is a serious condition that affects approximately 6% of all neonates born today in the U.S. and which is increasing rapidly in incidence because of this epidemic. Availability of a rapid screening test that can be administered at the point of care to all neonates would allow for early intervention, reducing costs of treatment and reducing pain and suffering for this vulnerable and helpless patient population. Providing a platform to accurately monitor actual levels of these drugs and their metabolites in such patients would allow better-controlled use of these pain management treatments, personalized to the needs of the individual neonate, and would reduce the probability of addiction and resulting complications, which include deleterious neurological effects. The purpose of this FastTrack SBIR project is to expand upon preliminary results that a device can sensitively and accurately detect opioids and their primary urinary metabolites in one-microliter urine samples, in less than a minute after sample introduction into the device, and adapt the device into a point-of-care instrument for use in hospitals, clinics, and other venues in which such tests are likely to be deployed.

NOFO Title: HEAL Initiative: Effectiveness Trials to Optimize, Implement, Scale, and Sustain the Collaborative Care Model for Individuals with Opioid Use Disorders and Mental Health Conditions (U01 Clinical Trial Required)
NOFO Number: RFA-MH-19-525
Summary:

This study will refine and test a collaborative care model for patients with opioid use disorder (OUD) and major depression, post-traumatic stress disorder, or an anxiety disorder in primary care. The primary aims of the study are: (1) prototype and test elements of the research team’s collaborative care models; (2) conduct a randomized study of three collaborative care conditions to determine which is most effective in improving outcomes for people with OUD and mental health conditions: Augmented Usual Care, Collaborative Care, or Collaborative Care + Social Worker; (3) measure clinician and organizational-level factors associated with implementation to increase success; (4) conduct a cost evaluation of each collaborative care model; and (5) work with smaller and rural practices to develop and test effective strategies to manage OUD. Successful completion of this study will provide evidence regarding the elements of integrated collaborative care required to maximize outcomes for individuals with OUD and psychiatric disorders.

NOFO Title: HEAL Initiative: HEALthy Brain and Child Development Study (HEALthy BCD) (R34 Clinical Trial Not Allowed)
NOFO Number: RFA-DA-19-036
Summary:

Structural and functional neuroimaging measures are prone to errors induced by subject motion. Many comorbid features of opioid exposure are likely to increase children’s in-scanner motion. In total, this raises substantial concern that existing neuroimaging methods are not sufficiently motion-robust to be used in studies of children ages 3–5. Researchers will address these concerns with a feasibility study, comparing the existing methods developed for the Adolescent Brain Cognitive Development (ABCD) study with novel methods we will develop and optimize for young children. They will evaluate research methods in a sample of 100 children and test whether novel technologies improve the quality of the raw imaging data and reduce motion biases in the derived measures. Researchers will determine predictors of successful imaging to inform sampling strategies in future studies. The primary outcomes will be novel, validated structural and functional neuroimaging imaging methods for young children and feasibility data to inform the design of future studies addressing developmental questions, particularly those related to opioid exposure.

NOFO Title: HEAL Initiative: Neonatal Opioid Withdrawal Syndrome Pharmacological Treatments Comparative Effectiveness Trial - Clinical Sites (UG1 Clinical Trial Required)
NOFO Number: RFA-HD-21-031
Summary:

Neonatal Opioid Withdrawal Syndrome (NOWS) is a condition that occurs when newborns are exposed to opioids during pregnancy. Symptoms often include tremors, excessive crying, sleep deprivation, and swallowing difficulties. Cases are rising, with a newborn affected by NOWS approximately every 15 minutes. Currently, healthcare providers in the United States lack standard, evidence-based treatments for NOWS. 

This project is part of a multi-center, randomized controlled clinical trial that directly compares NOWS treatments—morphine, methadone, and buprenorphine—and takes into account other types of non-drug therapies, such as behavioral interventions. The goal is to generate results that can inform clinical practice guidelines and give newborns with NOWS the best start possible. 

Thomas Jefferson University has more than 40 years of experience optimizing approaches to the care of opioid use disorder in pregnancy and conducts clinical research on NOWS treatments. The hospital provides a robust continuum of care that supports women with opioid use disorders before, during, and after delivery. This supportive culture has resulted in a relatively high rate of clinical trial participation that will enable long-term follow up of mothers and infants.

NOFO Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
NOFO Number: RFA-DA-19-002
Summary:

The adverse effects of morphine and other mu-opioid receptor (MOR) agonists are linked to the ?-arrestin pathway, while analgesia is tied to the G-protein pathway. Pathway specific or “biased” drug development can target G-protein specific agonists that avoid the negative consequences of ?-arrestin signaling activation and produce analgesia. Highly “biased” MOR agonists have promise as effective analgesics but devoid of opioid-induced adverse effects. Preclinical studies compared two compounds, MEB-1166 and MEB-1170, against Oliceridine and morphine. Both compounds displayed no respiratory depression, even at high doses, while morphine and Oliceridine significantly reduced respiratory function. In contrast to morphine, neither MEB-1166 nor MEB-1170 produced conditioned place preference, suggesting an absence of abuse liability. This study will characterize the pharmaceutical and pharmacological profiles and perform liability studies for these compounds.

NOFO Title: HEAL Initiative: America’s Startups and Small Businesses Build Technologies to Stop the Opioid Crisis (R43/R44 - Clinical Trial Optional)
NOFO Number: RFA-DA-19-019
Summary:

Effective medication-based treatment could prevent overdose deaths and help individuals recover from opioid use disorder, but only a fraction of those in need access treatment or receive a medication approved by the U.S. Food and Drug Administration. One way to improve people’s choice to seek and stay in treatment is to improve training for addiction treatment counselors beyond current methods that rely on brief online or in-person workshops. The goal of this research project is to develop and evaluate the technical feasibility and commercial viability of a scalable digital program to train behavioral addiction professionals in Community Reinforcement and Family Training (CRAFT), an evidence-based approach to increase treatment entry, using ongoing counselor training with feedback and coaching.