TRV734 for Opioid Use Disorder
Palo Alto (17 mi)Overseen byDavid H Epstein, Ph.D.
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: National Institute on Drug Abuse (NIDA)
Prior Safety Data
Trial Summary
What is the purpose of this trial?Background:
People with opioid-use disorder (OUD) might benefit from having more treatment drugs to choose from. A new drug, TRV734, could be used like methadone to treat OUD. It might not have as many side effects.
Objective:
To test if TRV734 relieves withdrawal symptoms and has fewer side effects than oxycodone in people with OUD.
Eligibility:
People ages 18-75 who have been receiving daily treatment with methadone for opioid use disorder for at least 3 months
Design:
Participants will be screened under Protocol 415. They will be screened with:
Medical, social, and psychiatric history
Physical exam
Electrocardiogram (ECG). For this, sticky pads will be placed on the participant s chest to monitor their heartbeat.
Blood and urine tests
Participants will stay in a residential unit for 13-21 days.
Most days, participants will receive their regular daily dose of methadone.
On 4 or 5 occasions, 3-4 days apart, participants will skip two doses of methadone in a row. About 4 hours after they skip the second dose, they will have an IV catheter inserted with a needle so that blood samples can be taken. They will take capsules of either oxycodone, a placebo, or the study drug. They will have an ECG. They will complete questionnaires. Their blood pressure, pupil size, and alertness will be tested. They will then take their usual dose of methadone.
Participants will give daily urine and breath samples.
What safety data exists for TRV734 in treating opioid use disorder?The provided research does not contain specific safety data for TRV734 in treating opioid use disorder. The articles discuss general strategies for opioid safety, abuse-deterrent properties of opioids, and management of opioid use disorder, but do not mention TRV734 or its safety data.13568
Is the drug TRV734 a promising treatment for opioid use disorder?The information provided does not directly mention TRV734, so we cannot determine if it is a promising treatment for opioid use disorder based on the given research articles.3671011
What data supports the idea that TRV734 for Opioid Use Disorder is an effective drug?The available research does not provide specific data on the effectiveness of TRV734 for treating Opioid Use Disorder. Instead, it discusses other treatments like methadone, buprenorphine, and naltrexone, which are known to reduce opioid use and improve outcomes. Without specific data on TRV734, it's unclear how it compares to these established treatments.246912
Do I have to stop taking my current medications for the trial?The trial does not specify if you need to stop all current medications, but you must continue your methadone treatment. You cannot take medications that could alter the effects of the opioid agonists being studied, like strong CYP3A4 inhibitors or inducers, or medications that could reduce opioid withdrawal symptoms.
Eligibility Criteria
Adults aged 18-75 with opioid use disorder, on methadone treatment for at least 3 months, willing to skip doses and provide blood samples. Women must not be pregnant or breastfeeding and agree to contraception; men must practice abstinence or use barrier contraception.Inclusion Criteria
I am between 18 and 75 years old.
Exclusion Criteria
I have been diagnosed with severe depression that is not currently under control.
I was unable to pass the consent understanding test for the study.
I have no conditions that affect blood or urine tests.
I do not have any serious health issues that would make research participation unsafe.
I am not pregnant or breastfeeding.
Treatment Details
The trial is testing TRV734's effectiveness in relieving withdrawal symptoms compared to oxycodone, without as many side effects. Participants will stay in a unit for up to three weeks, receive their regular methadone dose, occasionally skip it for testing purposes, and take either the study drug, placebo or oxycodone.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: TRV734Experimental Treatment1 Intervention
TRV734 at different doses vs. oxycodone for withdrawal suppression
Group II: PlaceboPlacebo Group1 Intervention
Placebo capsule
Find a clinic near you
Research locations nearbySelect from list below to view details:
National Institute on Drug AbuseBaltimore, MD
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Who is running the clinical trial?
National Institute on Drug Abuse (NIDA)Lead Sponsor
References
Serious adverse events in the Australian National Evaluation of Pharmacotherapies for Opioid Dependence (NEPOD). [2022]The study estimated serious adverse event (SAE) rates among entrants to pharmacotherapies for opioid dependence, during treatment and after leaving treatment.
Pharmacological enhancement of naltrexone treatment for opioid dependence: a review. [2021]PURPOSE: Opioid dependence (OD) is a serious and growing clinical condition with increasing social costs that requires expanding treatment beyond opioid agonist substitution. The opioid antagonist naltrexone has displayed a remarkable association of theoretical effectiveness and poor clinical utility in treating OD due to noncompliant behavior and low acceptability among patients, only partly modified by psychosocial interventions. We reviewed pharmacological studies, including naltrexone depot formulations and combination treatments. METHOD: We searched PubMed for clinical studies on the use of naltrexone implants and slow-release injections in OD, and investigations using adjunct medications to improve naltrexone maintenance therapy of OD. We discussed the results in view of their application to the clinical practice. RESULTS: Significant reduction in opioid use and improved retention in treatment have been found in several studies using depot naltrexone formulations, some of which are controlled clinical trials. Pilot investigations have gathered initial positive results on the use of naltrexone in combination with serotonin reuptake inhibitors, α-2 adrenergic, opioid, and γ-aminobutyric acid agonist medications. CONCLUSION: Current evidence suggests that more research on effectiveness and safety is needed in support of depot naltrexone treatment for OD. Further research comparing slow-release with oral naltrexone and opioid agonist medications will help characterize the role of opioid antagonist-mediated treatment of OD. Preliminary investigations on naltrexone combination treatments suggest the opportunity to continue study of new mixed receptor activities for the treatment of OD and other drug addictions.
Coupling Genetic Addiction Risk Score (GARS) with Electrotherapy: Fighting Iatrogenic Opioid Dependence. [2021]The endemic of legal opioid iatrogenic induced prescription drug abuse is of major world-wide concern. Understanding pain pathways and the role of dopaminergic tone in the neurophysiology of pain relief provides potential therapeutic solutions. A 2011 NIDA report indicated that approximately 8.7% of the entire US population above the age of 12 years has used a psychoactive drug within the past 30 days. It has been reported that the overall genetic contribution to the variance of Substance Use Disorder (SUD) was approximately 60% but each candidate gene evaluated by GWAS was relatively small. In an attempt to combat this global endemic we are proposing a number of alternative strategies. Prevention of death due to opioid overdose and attenuation of prescription abuse should focus on strategies that target 1) high-dosage medical users; 2) persons who seek care from multiple doctors; 3) persons involved in "drug diversion"; 4) genetic testing for addiction liability and severity indices; 5) non-pharmacolgical analgesic treatments such as electrotherapy.
Effect of Buprenorphine Implants on Illicit Opioid Use Among Abstinent Adults With Opioid Dependence Treated With Sublingual Buprenorphine: A Randomized Clinical Trial. [2016]The effectiveness of buprenorphine treatment of opioid dependence is limited by suboptimal medication adherence, abuse, and diversion.
Opioids with abuse-deterrent properties: A regulatory and technological overview. [2018]Three concurrent public health problems coexist in the United States: endemic nonmedical use/misuse of opioid analgesics, epidemic overdose fatalities involving opioid analgesics, and endemic chronic pain in adults. These intertwined issues comprise an opioid crisis that has spurred the development of formulations of opioids with abuse-deterrent properties and label claims (OADP). To reduce abuse and misuse of prescription opioids, the federal Food and Drug Administration (FDA) has issued a formal Guidance to drug developers that delineates four categories of testing to generate data sufficient for a description of a product's abuse-deterrent properties, along with associated claims, in its Full Prescribing Information (FPI). This article reviews the epidemiology of the crisis as background for the development of OADP, summarizes the FDA Guidance for Industry regarding abuse-deterrent technologies, and provides an overview of some technologies that are currently employed or are under study for incorporation into OADP. Such technologies include physical and chemical barriers to abuse, combined formulations of opioid agonists and antagonists, inclusion of aversive agents, use of delivery systems that deter abuse, development of new molecular entities and prodrugs, and formulation of products that include some combination of these approaches. Opioids employing these novel technologies are one part of a comprehensive intervention strategy that can deter abuse of prescription opioid analgesics without creating barriers to the safe use of prescription opioids. The maximal public health contribution of OADP will probably occur only when all opioids have FDA-recognized abuse-deterrent properties and label claims.
Management of opioid use disorder in the USA: present status and future directions. [2019]Opioid use disorder is characterised by the persistent use of opioids despite the adverse consequences of its use. The disorder is associated with a range of mental and general medical comorbid disorders, and with increased mortality. Although genetics are important in opioid use disorder, younger age, male sex, and lower educational attainment level and income, increase the risk of opioid use disorder, as do certain psychiatric disorders (eg, other substance use disorders and mood disorders). The medications for opioid use disorder, which include methadone, buprenorphine, and extended-release naltrexone, significantly improve opioid use disorder outcomes. However, the effectiveness of medications for opioid use disorder is limited by problems at all levels of the care cascade, including diagnosis, entry into treatment, and retention in treatment. There is an urgent need for expanding the use of medications for opioid use disorder, including training of health-care professionals in the treatment and prevention of opioid use disorder, and for development of alternative medications and new models of care to expand capabilities for personalised interventions.
The association between the OPRM1 A118G polymorphism and addiction in a Turkish population. [2020]Susceptibility to addiction has a complex genetic basis that includes genes associated with the action and metabolism of drugs of abuse. One important gene in that respect is OPRM1, which codes for the μ-opioid receptor and has an important role in mediating the rewarding effects of addiction substances. The aim of our study was to assess the prevalence of the OPRM1 A118G polymorphism (rs1799971) in Turkish population and to investigate its association with opioid and other substance addiction. In addition, we examined the association of rs1799971 in addicted patients who were also diagnosed with psychiatric disorders. The study included 103 patients addicted to opioids, cocaine, ecstasy, alcohol, lysergic acid diethylamide (LSD), cannabis, and sedative/hypnotic substances and 83 healthy volunteers with similar demographic features as controls. rs1799971 polymorphisms were identified with the polymerase chain reaction restriction fragment length polymorphism method (PCR-RFLP). The genotype frequencies were significantly higher in the addicted patients than controls (32.0 % vs 16.9 %, respectively; p=0.027). The prevalence of the G allele was 16.1 % in the addicted group and 8.4 % in the control group (p=0.031). Our study confirmed the association between the rs1799971(G) allele frequency and opioid and other substance addiction, but not with psychiatric disorders.
A Research Agenda for Advancing Strategies to Improve Opioid Safety: Findings from a VHA State of the Art Conference. [2021]US military Veterans have been disproportionately impacted by the US opioid overdose crisis. In the fall of 2019, the Veterans Health Administration (VHA) convened a state-of-the-art (SOTA) conference to develop research priorities for advancing the science and clinical practice of opioid safety, including both use of opioid analgesics and managing opioid use disorder. We present the methods and consensus recommendations from the SOTA. A core group of researchers and VA clinical stakeholders defined three areas of focus for the SOTA: managing opioid use disorder, long-term opioid therapy for pain including consideration for opioid tapering, and treatment of co-occurring pain and substance use disorders. The SOTA participants divided into three workgroups and identified key questions and seminal studies related to those three areas of focus. The strongest recommendations included testing implementation strategies in the VHA for expanding access to medication treatment for opioid use disorder, testing collaborative tapering programs for patients prescribed long-term opioids, and larger trials of behavioral and exercise/movement interventions for pain among patients with substance use disorders.
Prior National Drug Abuse Treatment Clinical Trials Network (CTN) opioid use disorder trials as background and rationale for NIDA CTN-0100 "optimizing retention, duration and discontinuation strategies for opioid use disorder pharmacotherapy (RDD)". [2021]Opioid use disorder continues to be a significant problem in the United States and worldwide. Three medications-methadone, buprenorphine, and extended-release injectable naltrexone,- are efficacious for treating opioid use disorder (OUD). However, the utility of these medications is limited, in part due to poor rates of retention in treatment. In addition, minimum recovery milestones and other factors that influence when and whether individuals can safely discontinue medications are unknown. The National Drug Abuse Treatment Clinical Trials Network (CTN) study "Optimizing Retention, Duration, and Discontinuation Strategies for Opioid Use Disorder Pharmacotherapy" (RDD; CTN-0100) will be among the largest clinical trials on treatment of OUD yet conducted, consisting of two phases, the Retention phase, and the Duration-Discontinuation phase. The Retention phase, open to patients initiating treatment, will test different doses and formulations of buprenorphine (standard dose sublingual, high dose sublingual, or extended-release injection), and a digital therapeutic app delivering contingency management and cognitive behavioral counseling on the primary outcome of retention in treatment. The Discontinuation phase, open to patients in stable remission from OUD and choosing to discontinue medication (including participants from the Retention phase or from the population of patients treated at the clinical site, referred by an outside prescriber or self-referred) will study different tapering strategies for buprenorphine (sublingual taper vs taper with injection buprenorphine), and a digital therapeutic app which provides resources to promote recovery, on the primary outcome of relapse-free discontinuation of medication. This paper describes how the RDD trial derives from two decades of research in the CTN. Initial trials (CTN-0001; CTN-0002; CTN-0003) focused on opioid detoxification, showing buprenorphine-naloxone was effective for detoxification, but that acute detoxification did not appear to be an effective treatment strategy. Trials on comparative effectiveness of medications for opioid use disorder (MOUD) (CTN-0027; CTN-0030; and CTN-0051) highlighted the problem of dropout from treatment and few trials defined retention on MOUD as the primary outcome. Long-term follow-up studies on those patient samples demonstrated the importance of long-term continuation of medication for many patients to sustain remission. Overall, these trials highlight the potential of a stable research infrastructure such as CTN to advance treatment effectiveness through a programmatic succession of large clinical trials.
Quantification of opioid dependence and abuse prevalence in the United States between 2017 and 2018. [2022]To quantify the prevalence of opioid drug dependence and abuse in United States between 2017 and 2018 and identify which opioid molecules are associated with a higher level of dependence and abuse.
Inhibitory Effects of a Novel μ-Opioid Receptor Nonpeptide Antagonist, UD-030, on Morphine-Induced Conditioned Place Preference. [2023]Although opioids are widely used to treat moderate to severe pain, opioid addiction and the opioid overdose epidemic are becoming more serious. Although opioid receptor antagonists/partial agonists, such as naltrexone and buprenorphine, have relatively low selectivity for the μ-opioid receptor (MOP), they have been used for the management of opioid use disorder. The utility of highly selective MOP antagonists remains to be evaluated. Here, we biologically and pharmacologically evaluated a novel nonpeptide ligand, UD-030, as a selective MOP antagonist. UD-030 had more than 100-fold higher binding affinity for the human MOP (Ki = 3.1 nM) than for δ-opioid, κ-opioid, and nociceptin receptors (Ki = 1800, 460, and 1800 nM, respectively) in competitive binding assays. The [35S]-GTPγS binding assay showed that UD-030 acts as a selective MOP full antagonist. The oral administration of UD-030 dose-dependently suppressed the acquisition and expression of morphine-induced conditioned place preference in C57BL/6J mice, and its effects were comparable to naltrexone. These results indicate the UD-030 may be a new candidate for the treatment of opioid use disorder, with characteristics that differ from traditional medications that are in clinical use.
Novel Therapeutic and Program-Based Approaches to Opioid Use Disorders. [2023]Opioid use disorder continues to drive overdose deaths in many countries, including the United States. Illicit fentanyl and its analogues have emerged as key contributors to the complications and mortality associated with opioid use disorder. Medications for opioid use disorder treatment, such as methadone and buprenorphine, are safe and substantially reduce opioid use, infectious complications, and mortality risk, but remain underutilized. Polysubstance use and emerging substances such as xylazine and designer benzodiazepines create additional treatment challenges. Recent clinical and policy innovations in treatment delivery, including telemedicine, bridge clinics, and expanded models for accessing methadone have the potential to increase access to life-saving care for people living with opioid use disorder. Expected final online publication date for the Annual Review of Medicine, Volume 75 is January 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.