Funded Projects

NOFO Title: Opioid Use Disorder in Pregnancy (R01)
NOFO Number: RFA-HD-18-036
Summary:

This study will challenge current clinical approaches to managing the pregnant woman with opioid use disorder. Dosing of buprenorphine (BUP) in pregnant women is based on studies in non-pregnant subjects, which suggests that symptoms of withdrawal occur when plasma BUP concentrations are < 1ng/ml. No such data exist for pregnant women, but this is a prerequisite for defining an appropriate dosing regimen of BUP in pregnant women. We will define this threshold by monitoring women undergoing mild, medically directed withdrawal. The Clinical Opioid Withdrawal Scale score and the Finnegan score for NAS are key to defining when withdrawal occurs and thus dictate treatment in mother and baby. Neither scoring system is based on plasma BUP concentrations and thus, may not reflect true opioid withdrawal. This proposal aims to develop physiologic-based scoring systems that refine the accuracy of diagnosis and optimize treatment.

NOFO Title: Development of a Device to Objectively Measure Pain (R43/R44)
NOFO Number: RFA-DA-18-012
Summary:

One of the most widely used treatments for chronic pain is opioid analgesics. Importantly, there is evidence of a pathological interaction between opioids and the immune system that can contribute to both opioid tolerance and elevated levels of pain. Chronic pain conditions for which opioids are most often prescribed have been shown to involve dysregulation of the immune system, which may contribute to pathological effects of opioid use in these patients. To address this unmet need, this study aims to develop a reliable, cost-effective, and non-invasive in vitro diagnostic assay for chronic pain with an underlying inflammatory pathology, as a blood test available in primary care settings, with the hope that doctors can use the test to identify which patients might benefit less from opioids and be more likely to become addicted.

NOFO Title: Mentored Research Scientist Development Award (Parent K01)
NOFO Number: PA-16-190
Summary:

Quality implementation of evidence-based programs (EBPs) in community settings for youth is critical for reducing the burden of alcohol, tobacco and other drug (ATOD) use and its consequences. EBPs delivered in schools are an efficient way to reach large populations of young people, including those underserved by other settings, and reduce and prevent ATOD use. Yet youth rarely receive EBPs as intended in community settings, including schools. This training and research plan will prepare the investigator to become an independent scholar in the implementation of theories and frameworks to better understand factors related to program delivery—approaches to enhancing ATOD programs for youth in community settings. More specifically, the training will allow him to expand the application of Consolidated Framework for Implementation Research (CFIR) to inform approaches to enhancing effective EBP delivery. The proposed training and research plan extends current implementation research to focus applying implementation theories, frameworks and strategies in other community settings (schools) and on economic evaluation of implementation strategies. The results are expected to improve current efforts to deliver EBPs in diverse community settings and aid in applying evidence-based implementation strategies in the school context to ultimately reduce and prevent ATOD use among youth.

NOFO Title: NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)
NOFO Number: PA-18-484
Summary:

Deaths from opioid overdose continue to rise; from 2015 to 2016, there was a 28 percent increase in the number of fatal overdoses. Currently available pharmacotherapies include MOR agonists (e.g., buprenorphine) and antagonists (e.g., naloxone), all of which suffer from specific and clear limitations. To address the main deficits in these treatments, the researchers will develop and optimize medications with longer duration of action that prevent and reverse the effects of opioids in a manner that is not surmounted by increasing doses of agonist. Their pilot studies in monkeys show that the pseudo irreversible MOR selective antagonist methocinnamox (MCAM) decreases heroin but not cocaine self-administration, decreases choice for remifentanil in a food/drug choice procedure, and reverses—as well as protects against—respiratory depression by heroin, with a single injection being effective for a week or longer. Bringing a medication like this to marketable fruition could significantly improve the treatment of OUD and save lives by providing insurmountable extended protection after rescue from overdose, including from ultra-potent fentanyl analogs.

NOFO Title: Loyalty and Reward-Based Technologies to Increase Adherence to Substance Use Disorder Pharmacotherapies (R43/R44 - Clinical Trial Optional)
NOFO Number: RFA-DA-19-014
Summary:

While effective treatments exist for substance use disorders, adhering to treatment and retaining patients in treatment can be a challenge. The objectives of this project are to facilitate the implementation of loyalty/reward-based programs to increase adherence to medical treatment among patients with substance use disorders through innovative solutions to common challenges. Building on experience developing software to promote patient appointment attendance, the project will build a new tool to test on a sample of 10 providers and 10 patients who are prescribed but not fully adherent to substance use disorder treatment. Patients will receive tailored text messages (in English or Spanish) encouraging adherence, self-report their treatment adherence (which will be verified through smart pill caps and biological testing), earn points for adherence that can be exchanged for rewards customized for them based on a baseline survey, and report their satisfaction with the program and process at the end of the 4-week study. This pilot will assess the feasibility and perceived usefulness of the product in support of eventual larger-scale testing in a clinical trial.

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

The Family School Partnership (FSP) and classroom-centered (CC) interventions targeted aggressive-coercive behavior and poor academic achievement as antecedents of the distal outcomes of antisocial behavior, substance abuse/dependence, psychiatric symptoms/disorders, high-risk sexual behavior and successful adaptation to the relevant developmental demands of the educational, work, romantic relationships and family (both family of procreation and origin/orientation) social fields/contexts. The participants of the FSP and CC original prevention trial were a population (n = 798) of urban, predominately African-American young adults, who began first grade in the fall of 1993 in nine elementary schools in predominantly low- to lower-middle-income Baltimore areas. The central purpose of the proposed study is to extend through ages 31-35 an examination of normal and pathogenic development and the impact of these two universal first-grade preventive interventions on the distal targets mentioned above. We will continue to study the role of phenotypic and genetic factors (and their interactions) as well as the impact of the interventions on the development and course of substance use/abuse/dependence, psychiatric symptoms/disorders, antisocial behavior/disorder and high-risk sexual behavior through young adulthood. The knowledge accrued over the course of the proposed assessments should serve to inform the nature, targets and timing of our future preventive intervention efforts.

NOFO Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
NOFO Number: DA19-002

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:

Maternal use and addiction to opioids or other drugs has resulted in an unprecedented rise in drug withdrawal complications in newborns known as neonatal abstinence syndrome (NAS). While there is no accepted standard for treating NAS, non-pharmacological bundles are recommended as an initial course of treatment. Unfortunately, non-pharmacological care (swaddling, rocking, frequent feedings, and skin contact) require significant use of human resources. This project studies the technical feasibility of a stochastic vibrotactile stimulation (SVS) technology incorporated into the hospital bassinet pad, which provides gentle vibrating sensory stimulation to soothe infants with NAS. Building on preliminary evidence that this type of stimulation calms NAS infants without altering their sleep, this study aims to develop a commercially viable bassinet pad that could be used in a hospital setting.

NOFO Title: Clinical Trials or Observational Studies of Behavioral Interventions for Prevention of Opioid Use Disorder or Adjunct to Medication Assisted Treatment-SAMHSA Opioid STR Grants (R21/R33)
NOFO Number: RFA-AT-18-002
Summary:

New Hampshire can anticipate as many as 1,000 infants born with prenatal opioid exposure each year. Pain management is complicated for pregnant women with opioid use disorder (OUD), and undermanagement of pain is a strong risk factor for relapse. Contemplative interventions, such as yoga and mindfulness, may reduce risks for relapse for pregnant and parenting women with OUD. This project represents a partnership with New Hampshire stakeholders to develop and pilot evaluation of a trauma-informed yoga and mindfulness relapse prevention intervention (Mindful Moms in Recovery: MMORE). It aims to: 1) identify needs and areas of adaptation of trauma-informed yoga and mindfulness-based relapse prevention protocols through formative work with pregnant and parenting woman; 2) develop an integrated 10-session intervention protocol with iterative feedback from client stakeholders; and 3) evaluate feasibility, acceptability, and efficacy trends of MMORE in a pre-post pilot with pregnant women.

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:

There is a need for longer-acting prophylactic pharmacologic options for opioid use disorder (OUD) patients during maintenance therapy. This study tests a titanium implant loaded with a formulation of naltrexone and a naturally occurring carboxylic acid. The device is implanted subcutaneously with local anesthetic during an in-office procedure. The technology is based on a unique formulation that keeps the pH within the reservoir low and promotes passive diffusion of naltrexone. The benefits of the product include complete medication adherence for one year after administration, fewer relapses, smooth profile ensuring complete prophylaxis without sub-therapeutic plasma troughs, full reversibility, and similar efficacy with less drug exposure. This technology has been validated clinically with another drug and tested preclinically with naltrexone. This project will finalize the chemistry manufacturing and controls, produce IND supplies, conduct an IND-enabling safety study, and submit the IND.

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

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:

As the opioid crisis claims more and more lives, there is a need to develop new, safer analgesics. Biased agonists could activate beneficial signaling pathways while avoiding those that cause adverse effects. This project aims to speed the discovery of non-addictive analgesics by providing drug discovery teams with simpler, more robust, more quantitative assays for agonist bias. The goal is to optimize and test new assays for agonist bias at NOP, D3 dopamine, CB1 cannabinoid, and OPRM1 opioid receptors, which couple to both the Gi and ?-arrestin signaling pathway, and create new tools to improve the analysis of structure/activity relationships that can be used in drug discovery and distribute to researchers who are developing new drugs for OUD.

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

This study will (1) test pharmacologic and behavioral strategies to improve OUD pharmacotherapy treatment retention and to improve outcomes among patients who have been successfully stabilized on OUD medications and want to stop medication and (2) identify predictors of successful outcome and develop a stage model of relapse risk.