CTN - 0051: Extended-Release Naltrexone vs. Buprenorphine for Opioid Treatment (X:BOT)
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA824589 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:CTN - 0051: Extended-Release Naltrexone vs. Buprenorphine for Opioid Treatment (X:BOT)
| PRJNA824587 | ENA
Project description:IntroductionFor opioid-dependent patients in the US and elsewhere, detoxification and counseling-only aftercare are treatment mainstays. Long-term abstinence is rarely achieved; many patients relapse and overdose after detoxification. Methadone, buprenorphine-naloxone (BUP-NX) and extended-release naltrexone (XR-NTX) can prevent opioid relapse but are underutilized. This study is intended to develop an evidence-base to help patients and providers make informed choices and to foster wider adoption of relapse-prevention pharmacotherapies.MethodsThe National Institute on Drug Abuse's Clinical Trials Network (CTN) study CTN-0051, X:BOT, is a comparative effectiveness study of treatment for 24weeks with XR-NTX, an opioid antagonist, versus BUP-NX, a high affinity partial opioid agonist, for opioid dependent patients initiating treatment at 8 short-term residential (detoxification) units and continuing care as outpatients. Up to 600 participants are randomized (1:1) to XR-NTX or BUP-NX.ResultsThe primary outcome is time to opioid relapse (i.e., loss of persistent abstinence) across the 24-week treatment phase. Differences between arms in the distribution of time-to-relapse will be compared (construction of the asymptotic 95% CI for the hazard ratio of the difference between arms). Secondary outcomes include proportions retained in treatment, rates of opioid abstinence, adverse events, cigarette, alcohol, and other drug use, and HIV risk behaviors; opioid cravings, quality of life, cognitive function, genetic moderators, and cost effectiveness.ConclusionsXR-NTX and BUP-NX differ considerably in their characteristics and clinical management; no studies to date have compared XR-NTX with buprenorphine maintenance. Study design choices and compromises inherent to a comparative effectiveness trial of distinct treatment regimens are reviewed.Clinical trial registrationNCT02032433.
| S-EPMC5416469 | biostudies-literature
Project description:The opioid epidemic represents a national crisis. Oxycodone is one of the most prescribed opioid medications in the United States, whereas buprenorphine is currently the most prescribed medication for opioid use disorder (OUD) pharmacotherapy. Given the extensive use of prescription opioids and the global opioid epidemic, it is essential to understand how opioids modulate brain cell type function at the single-cell level. We performed single nucleus RNA-seq (snRNA-seq) using iPSC-derived forebrain organoids from three male OUD subjects in response to oxycodone, buprenorphine, or vehicle for seven days. We utilized the snRNA-seq data to identify differentially expressed genes following drug treatment using the Seurat integrative analysis pipeline. We utilized iPSC-derived forebrain organoids and single-cell sequencing technology as an unbiased tool to study cell-type-specific and drug-specific transcriptional responses. After quality control filtering, we analyzed 25787 cells and identified sixteen clusters using unsupervised clustering analysis. Our results reveal distinct transcriptional responses to oxycodone and buprenorphine by iPSC-derived brain organoids from patients with OUD. Specifically, buprenorphine displayed a significant influence on transcription regulation in glial cells. However, oxycodone induced type I interferon signaling in many cell types, including neural cells in brain organoids. Finally, we demonstrate that oxycodone, but not buprenorphine activated STAT1 and induced the type I interferon signaling in patients with OUD. These data suggest that elevation of STAT1 expression associated with OUD might play a role in transcriptional regulation in response to oxycodone. In summary, our results provide novel mechanistic insight into drug action at single-cell resolution.
2024-07-18 | GSE210206 | GEO
Project description:Opioids are commonly prescribed to patients with advanced clear cell renal cell carcinoma for extended periods of time in assistance for pain management. Because extended opioid exposure has been shown to affect the vasculature and to be immunosuppressive, we investigated how it may affect the metabolism and physiology of advanced clear cell renal cell carcinoma. RNA sequencing of archived patient’s specimens with extended opioid exposure or non-opioid exposure were peformed.
2023-08-30 | GSE214563 | GEO
Project description:The opioid receptors are important regulators of pain, reward, and addiction. Limited evidence suggests the mu and delta opioid receptors form a heterodimer (MDOR), which may act as a negative feedback brake on opioid-induced analgesia. However, evidence for the MDOR in vivo is indirect and limited, and there are few selective tools available. We recently published the first MDOR-selective antagonist, D24M, allowing us to test the role of the MDOR in mice. We thus co-treated CD-1 mice with D24M and opioids in tail flick, paw incision, and chemotherapy-induced peripheral neuropathy pain models. D24M treatment enhanced oxymorphone anti-nociception in all models by 52.3%-628%. This enhancement could not be replicated with the mu and delta selective antagonists CTAP and naltrindole, and D24M had a mild transient effect in the Rotarod test, suggesting this increase is selective to the MDOR. However, D24M had no effect on morphine or buprenorphine, suggesting that only specific opioids interact with the MDOR. To find a mechanism we performed phosphoproteomic analysis on brainstems of mice. We found that the kinases Src and CaMKII were repressed by oxymorphone, which was restored by D24M. We were able to confirm the role of Src and CaMKII in D24M-enhanced anti-nociception using small molecule inhibitors (KN93, Src-I1). Together these results provide direct in vivo evidence that the MDOR acts as an opioid negative feedback brake, which occurs via the repression of Src and CaMKII signal transduction. These results further suggest that MDOR antagonism could be a means to improve clinical opioid therapy.
2023-03-10 | PXD022106 | Pride
Project description:In this study, we aimed to adopt the transcriptome sequencing technology to obtain the different changes of transcriptome profiles after infecting with CTN in human neuroblastoma cell line SH-SY5Y. And then, through systematic bioinformatics analysis, we hope to find useful clues for the pathogenesis of Rabies.
2021-08-24 | GSE151890 | GEO
Project description:Opioid-use disorder (OUD) during pregnancy has increased in the United States to critical levels and is a leading cause of maternal morbidity and mortality. Untreated OUD is associated with pregnancy complications in particular, preterm birth. Medications for OUD, such as buprenorphine, are recommended with the added benefit that treatment during pregnancy increases treatment post-partum. However, the rate of preterm birth in individuals using illicit opioids or being treated with opioid agonist therapeutics is double that of the general population. Since inflammation in the placenta and fetal membranes (FM) is a common underlying cause of preterm birth, we sought to determine if the opioid, buprenorphine, induces sterile inflammation in human FMs and to examine the mechanisms involved. Using an established in vitro human FM explant system, we report that buprenorphine significantly increased FM secretion of the inflammatory cytokine IL-6; the neutrophilic chemokine IL-8; and the inflammasome-mediated cytokine IL-1b, mirroring the inflammatory profile commonly seen at the maternal-fetal interface in preterm birth. Other factors that were elevated in FMs exposed to buprenorphine included the mediators of membrane weakening, prostaglandin E2 (PGE2), and the matrix metalloproteinases, MMP1 and MMP9. Furthermore, this sterile inflammatory and weakening FM response induced by buprenorphine was mediated in part by innate immune Toll-like receptor 4 (TLR4), the NLRP3 inflammasome, the m-opioid receptor, and downstream NFkB and ERK/JNK/MAPK signaling. This may provide the mechanistic link between opioid use in pregnancy and the elevated risk for preterm birth. Since there are adverse consequences of not treating OUD, our findings may help identify ways to mitigate the impact opioids have on pregnancy outcomes while allowing the continuation of maintenance therapy.
2025-02-07 | GSE282727 | GEO
Project description:Helicobacter cinaedi MRY12-0051 genome sequencing project
| PRJDB5659 | ENA
Project description:We report the transcriptome and miRNAome of human embryonic kidney 293 cells upon the administration of ochratoxin A (OTA) and citrinin (CTN), to compare the individual and combined toxicity of these two mycotoxins. We identified largely differentially expressed miRNAs and corresponding genes, and the correlations between miRNAs and their target genes associated with apoptotic signaling were furthermore analyzed by pmi-RB-REPORT luciferase assay system. We concluded that hsa-miR-1-3p plays an essential role in promoting OTA and CTN-induced renal cytotoxicity.
2017-12-31 | GSE93148 | GEO
Project description:Transcriptome analysis induced by CTN infection
| PRJNA637596 | ENA