A PHASE II CLINICAL TRIAL FOR THE EVALUATION OF THE EFFICACY OF DISULFIRAM/COPPER COMBINATION AS AN ADJUVANT AND CONCURRENT CHEMOTHERAPY IN THE TREATMENT OF NEWLY DIAGNOSED GLIOBLASTOMA MULTIFORM

Glioblastoma multiform (GBM) is the most common malignant primary brain tumor in adults. Despite maximal treatment tumor relapse occurs regularly accompanied by unfavourable prognosis. Among other reasons, it is believed that this could be in part due to the existence of the so-called tumor stem cells (TSCs), a cellular subfraction within GBM which escape therapy by being highly resistant to irradiation and chemotherapy and thus constituting the source of tumor recurrence.
GBM, like many other cancers, show a sub-population of aldehyde dehydrogenase (ALDH) overexpressing TSCs. More specifically, ALDH1A1, a cytoplasmatic isoform of ALDH, proved to be a novel stem cell marker in human GBM. In addition, ALDH1A1 has been shown to be a mediator for resistance of GBM to temozolomide (TMZ) and a reliable predictor of clinical outcome; prognosis of patients with a high level of ALDH1A1 expression was poor compared with that of patients with low levels. Consequently, ALDH1A1 may serve as a potential target to improve treatment of human GBM through inhibition of the enzyme.
Disulfiram (DSF) has been used for more than sixty years in the treatment of chronic alcoholism because of the unpleasant symptoms it provokes after ethanol intake. The underlying mechanism is believed to be the accumulation of acetaldehyde in the blood, due to inhibition of the liver ALDHs. Actually, DSF is a strong inhibitor of ALDH1A1 and relatively non-toxic at therapeutic (for chronic alcoholism) doses that can penetrate the blood-brain barrier. In addition, DSF has been shown to be cytotoxic on GBM stem-like cells, inhibiting the growth of TMZ resistant GBM cells and blocking self-renewal by
100% , while it has been identified as an inhibitor of human GBM stem cells in high-throughput chemical screens. Interestingly, a number of these actions were copper-dependent.
In the current Phase II clinical trial, DSF/copper combination will be tested as an adjunctive and concurrent chemotherapy in the treatment of newly diagnosed GBM. According to our hypothesis, initiation of DSF chemotherapy after the resection of the tumor and before the introduction of the standard radio-chemotherapy will inhibit ALDH1A1 of GBM TSCs making them more susceptible to radio-chemotherapy and possibly reducing the recurrence rate of GBM. On the other hand, the addition of copper will probably enhance the cytotoxic effects of DSF possibly through augmentation of its pro-apoptotic and proteasomal inhibitory actions.

开始日期2027-01-01

申办/合作机构

Universität Ulm

[+2]

NCT06793488

/ Recruiting早期临床1期IIT

Neural Mechanisms of Anxiety During Early and Protracted Abstinence in Alcohol Use Disorder

The goal of this study is to better understand the underlying neurobiological basis of anxiety that emerges during abstinence in patients with alcohol use disorder (AUD). The main questions it aims to answer are:
1. To characterize anxiety itself as well as anxiety related-neurobiological circuitry in early abstinence in AUD
2. To examine how anxiety and anxiety related-neurobiological circuitry change over the course of abstinence in AUD
Researchers will recruit both participants with AUD and healthy volunteers.
The participants with AUD will be prescribed disulfiram, a medication that helps participants with AUD stay abstinent. Healthy volunteers will not receive antabuse. Patients with AUD will undergo fMRI scanning both after 1 week and 3 months of disulfiram treatment. Healthy volunteers will undergo fMRI once.

开始日期2025-08-29

申办/合作机构

The Trustees of Columbia University in The City of New York

[+1]

NCT06319872

/ Recruiting临床1期IIT

The Effects of Disulfiram on Visual Acuity in Patients With Retinal Degeneration

Oral disulfiram (Antabuse®) has been shown to improve image-forming vision in animal models with retinal degeneration due to its ability to decrease Retinoic Acid synthesis and consequently reduce hyperactivity in the inner retina. The investigator will aim to evaluate the impact of oral disulfiram on the vision of patients with retinal degeneration who are being treated with the drug in the management of their concurrent alcohol use disorder.

开始日期2025-05-19

申办/合作机构

University of Rochester

100 项与双硫仑相关的临床结果

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100 项与双硫仑相关的转化医学

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100 项与双硫仑相关的专利（医药）

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项与双硫仑相关的文献（医药）

2025-12-31·RENAL FAILURE

Identification of biomarkers for chronic renal fibrosis and their relationship with immune infiltration and cell death

Article

作者: Chen, Yinhao ; Wang, Rong ; Chen, Xiaolan ; Shen, Hao ; Sha, Haonan ; Shi, Jiaqi ; Qin, Xinyue

BACKGROUND:

Chronic kidney disease (CKD) represents a significant global public health challenge. This study aims to identify biomarkers of renal fibrosis and elucidate the relationship between unilateral ureteral obstruction (UUO), immune infiltration, and cell death.

METHODS:

Gene expression matrices for UUO were retrieved from the gene expression omnibus (GSE36496, GSE79443, GSE217650, and GSE217654). Seven genes identified through Protein-Protein Interaction (PPI) network and Support Vector Machine-Recursive Feature Elimination (SVM-RFE) analysis were validated using qRT-PCR in both in vivo and in vitro UUO experiments. WB assays were employed to investigate the role of Clec4n within NF-κB signaling pathway in renal fibrosis. The composition of immune cells in UUO was assessed using CIBERSORT, and gene set variant analysis (GSVA) was utilized to evaluate prevalent signaling pathways and cell death indices.

RESULTS:

GO and KEGG enrichment analyses revealed numerous inflammation-related pathways significantly enriched in UUO conditions. Bcl2a1b, Clec4n, and Col1a1 were identified as potential diagnostic biomarkers for UUO. Analysis of immune cell infiltration indicated a correlation between UUO and enhanced mast cell activation. Silencing Clec4n expression appeared to mitigate the inflammatory response in renal fibrosis. GSVA results indicated elevated inflammatory pathway scores in UUO, with significant differences in disulfiram and cuproptosis scores compared to those in the normal murine kidney group.

CONCLUSION:

Bcl2a1b, Clec4n, and Col1a1 may serve as biomarkers for diagnosing UUO. UUO development is closely linked to immune cell infiltration, activation of inflammatory pathways, disulfiram, and cuproptosis processes.

2025-12-01·LUNG

Disulfiram Alleviates MTX-Induced Pulmonary Fibrosis by Inhibiting EMT in Type 2 Alveolar Epithelial Cells

Article

作者: Li, Rong ; Zhang, Linyi ; Zhang, Zhaohua ; Wang, Chunyang ; Xu, Hong ; Ma, Ziyi ; Lan, Kai ; Wu, Xiaohui ; Chen, Min

PURPOSE:

Methotrexate (MTX)-induced pulmonary fibrosis is associated with high morbidity and mortality, with limited treatment options available. This study investigates whether disulfiram (DSF) can mitigate MTX-induced pulmonary fibrosis and explores the underlying mechanisms.

METHODS:

Eight-week-old male mice were divided into control, DSF, MTX, and MTX+DSF groups and treated for 8 weeks. Weight, food, and water intake were monitored. Post-treatment, lung tissues were analyzed using HE and Masson staining, and electron microscopy. Real-time qPCR and ELISA were employed to assess inflammatory markers such as IL-1β and TNF-α in lung tissues and serum. PCR, ELISA, and Western blot were used for fibrotic markers including Col1α1, α-SMA, and hydroxyproline. Type 2 alveolar epithelial cell line MLE12 cells were similarly grouped, followed by RNA sequencing and bioinformatics analysis to elucidate the mechanisms by which DSF exerts anti-MTX-induced pulmonary fibrosis effects. ELISA and Western blot were used to measure E-cadherin and α-SMA expression.

RESULTS:

DSF significantly reduced MTX-induced alveolar septal thickening, pulmonary fibrosis, and inflammatory cell infiltration. It also decreased the expression of inflammatory factors IL-1β and TNF-α, as well as the expression of Col1α1, α-SMA, and others. RNA-seq revealed that DSF induces changes in multiple signaling pathways associated with pulmonary fibrosis, particularly in extracellular matrix-related genes. ELISA and Western blot showed decreased E-cadherin and increased α-SMA in the MTX group, which was partially restored with DSF treatment.

CONCLUSION:

DSF alleviates MTX-induced pulmonary fibrosis by reducing epithelial-mesenchymal transition (EMT) in type 2 alveolar epithelial cells. Disulfiram shows potential as a therapeutic agent for MTX-induced pulmonary fibrosis.

2025-12-01·BIOMATERIALS

Infected microenvironment responsive nanoprodrug for the specific therapeutics of Helicobacter pylori clearance

Article

作者: Sun, Yue ; Jiang, Jingwen ; Zhao, Chunshun ; Lin, Huanxin ; Zheng, Dong ; Zeng, Zishan ; Li, Wanzhen

Helicobacter pylori (H. pylori) is considered as the major pathogenic factor related to multiple digestive diseases. However, the efficacy of first-line treatment containing antibiotics gradually declined. It is urgent to develop treatment with antibiotic reduction/abandonment to combat H. pylori. Based on our previous discovery that Cu(DTC)₂ exhibited stronger bactericidal effect than that of disulfiram or diethyldithiocarbamate (DTC), we constructed an antibiotic-free therapeutic strategy composed of DTC prodrug, Cu²⁺ and shikonin (SK) to eliminate H. pylori. DTC was firstly modified with nitroaromatic moiety to acquire DTC prodrug (NTR-DTC), which was further encapsulated into Cu-SK@DOPA to construct nanoprodrug Cu-SK@NTR-DTC to achieve the triple masking of DTC, Cu²⁺ and SK for the specificity therapeutics. Cu-SK@NTR-DTC could penetrate mucus layer and mainly detain in the bacteria infection area. In the presence of H. pylori, DTC was released from NTR-DTC to recover activity of copper chelation, and competitively bound Cu²⁺ from Cu-SK to form Cu(DTC)₂. The released SK possessed the bactericidal sensitization effect on Cu(DTC)₂. The H. pylori-activable dissociation of Cu-SK@NTR-DTC, and the local release of Cu(DTC)₂ and SK seriously destructed the bacterial membranes integrity and induce H. pylori death, which provided a feasible strategy to address the clinical limitations of H. pylori clearance.

项与双硫仑相关的新闻（医药）

2025-03-24

·Pharmaceutical Technology

Tempero secures $70m to advance addiction treatment candidate

The venture firm 8VC led the Series B funding round to support Tempero, which is developing treatments for substance use disorders. Credit: Ekaterina Chizhevskaya via Getty Images. Tempero Bio has raised $70m in Series B financing to advance its lead candidate TMP-301 through two clinical trials for alcohol use disorder (AUD) and cocaine use disorder (CUD). 8VC led the Series B round, with participation from Aditum Bio, Khosla Ventures, and other investors. The capital will support Phase III-enabling activities, preclinical studies for additional indications, and new formulations of TMP-301, as per the 24 March announcement. TMP-301 is a metabotropic glutamate receptor 5 (mGluR5)-negative allosteric modulator (NAM), which plays a role in central nervous system function. Tempero said that the candidate can prevent relapse by “targeting the underlying biology of addiction”. US-based Tempero has kicked off two clinical studies to support TMP-301’s development. This includes a Phase II trial evaluating TMP-301’s safety and efficacy in patients with AUD (NCT06648655), and a drug-drug interaction (DDI) study (NCT06648668) assessing the mGluR5-targeting candidate in individuals using cocaine. A full Phase II study in CUD is planned once the DDI study concludes. TMP-301 has shown promise in preclinical models of alcohol, cocaine, and opioid use disorder (OUD), and demonstrated safety and tolerability in Phase I studies involving over 80 healthy volunteers. Tempero was launched in 2020 by Aditum Bio, the investment firm founded by former Novartis executives Joe Jimenez and Mark Fishman, in partnership with pharmaceutical company Sosei Heptares. Sosei licenced TMP-301 to Tempero in return for an upfront payment and strategic equity stake in Tempero. Despite the public health burden of alcohol use disorder and cocaine use disorder, treatment options remain limited. Only three US Food and Drug Administration (FDA)-approved medications exist for alcohol use disorder, Antabuse (disulfiram), Revia/Vivitrol (naltrexone), and Campral (acamprosate). However, research from the US non-profit, the Federation of American Scientists (FAS), indicates they are only prescribed to around 2% of persons with AUD in the US. In the announcement accompanying the funding, Ricardo Dolmetsch, chief scientific officer of Tempero Bio said: “Substance use disorders affect 48 million Americans and contribute to more than 100,000 deaths per year. We urgently need more effective treatments to help patients and families with these diseases.” Beyond mGluR5 modulation, several other approaches are emerging. Glucagon- like receptor 1 agonists (GLP-1RAs), currently used for diabetes and weight loss, are being investigated for their potential to curb alcohol use and opioid addiction, signalling a shift in how substance use disorders may be treated in the future. mGluR5 modulation is also being explored in other indications. In January 2024, Switzerland-based Stalica raised $17.5m in Series B financing to fund clinical trials for its mGluR5-targeting candidate mavoglurant. Stalica signed an in-licencing agreement with Novartis to develop the drug as a treatment for substance use disorders and neurodevelopmental disorders (NDDs) in January 2023. The company is planning a Phase III trial for mavoglurant in patients with cocaine use disorder later in 2025.

临床2期临床1期临床3期临床结果

2025-03-09

·医学新视点

巴西风湿病学会：干燥综合征患者神经、认知、精神表现的临床评估及管理建议

原发性干燥病（Sjögren′s disease，SjD）是一种免疫介导的慢性、炎症性疾病，临床表现极为复杂。除常见的外分泌腺功能障碍外，神经和精神系统也常受影响，严重影响患者的生活质量、社会参与度和预后。然而，在SjD患者中，其神经和精神症状常被忽视，且尚未得到全面、系统的评估。鉴于SjD引起的神经、精神和认知障碍的病理生理学基础尚不完全清楚，且缺乏明确的诊断、调查及管理标准，当前的治疗策略主要遵循一般指导方针。因此，深入探索SjD患者神经和精神系统病变的病理机制，寻找共同的分子特征，并结合临床参数进行综合分析，对于提高诊断准确性、优化治疗方案及改善患者预后具有重要意义。巴西风湿病学会工作小组对原发性SjD的中枢、周围和自主神经系统表现的诊断和患病率进行了系统回顾，并提出针对性的诊断和管理建议，以期为临床实践提供新的思路与参考。研究共纳入51项研究，重点关注并分析了周围神经系统和中枢神经系统相关内容，并在此基础上制定了10条建议。 ▲选择用于荟萃分析的关于SjD的神经和精神表现的诊断和流行的研究流程图（图片来源：参考文献[1]) 主要观点 SjD的神经系统受累在解剖学上分为三大类：中枢神经系统、周围神经系统和自主神经系统。尽管欧洲抗风湿病联盟干燥综合征疾病活动指数（ESSDAI）这一疾病活动评估工具纳入了部分神经系统表现，但其并未对某些神经和精神方面的表现进行评估。神经系统症状可能比干燥症状早几年出现，这进一步增加了诊断SjD的困难性。与干燥综合征相关的神经和精神障碍展现了一个广泛且高度异质性的临床表现谱系，其中一些症状往往未被识别为潜在疾病的一部分。推荐意见 01 建议将ESSDAI作为诊断和评估SjD期间神经系统疾病活动的辅助工具。（同意度100%） 02 建议对患有神经系统综合征的患者进行SjD检查，即使患者没有出现干燥症状，尤其是当其他诊断线索无明显进展时。（同意度100%） 03 对于有自身免疫证据（如抗核抗体、抗Ro/SSA抗体、抗La/SSB抗体、冷球蛋白、类风湿因子）、存在生物标志物（高γ球蛋白血症、低补体水平）、有干燥症状或既往诊断为SjD的患者，建议关注神经系统疾病。（同意度100%） 04 建议对SjD和神经系统疾病患者进行管理，或与专业知识中心密切合作，采用多学科方法。（同意度100%）周围神经系统主要观点周围神经系统的表现通常与体质和内脏症状以及血清生物标志物的改变有关。这些情况可能与ESSDAI评估的较高疾病活动率相关，尽管该工具没有考虑到许多潜在的表现。周围神经系统受累比中枢神经受累更常见，其中一些可导致较差的生活质量和淋巴瘤的风险增加。周围神经病变患者的生存率似乎降低，尤其是那些患有多发性单神经炎的患者。 SjD的神经学表现需要特别注意与感染性疾病（麻风病和丙型肝炎病毒感染、人类免疫缺陷病毒感染、人类嗜T淋巴细胞病毒感染）、代谢性疾病（糖尿病）、遗传性疾病（法布雷病、淀粉样变性）、副蛋白血症和肿瘤、维生素B12和硒缺乏、酒精或药物毒性以及其他自身免疫性炎症性疾病（乳糜泻、重症肌无力和桥本氏甲状腺炎）进行鉴别诊断。一些与周围神经症状有关的药物包括抗生素（异烟肼、甲硝唑、乙胺丁醇、呋喃妥因、粘菌素、氨苯砜）、抗有丝分裂药物（长春新碱、顺铂、紫杉醇、阿霉素）、抗病毒药物（双脱氧肌苷、双脱氧胞苷、干扰素）以及其他药物（沙利度胺、秋水仙碱、金制剂、青霉胺、氯喹、环孢素、胺碘酮、苯妥英、双硫仑、碳酸锂片、西咪替丁）。推荐意见 05 建议在诊断时准确评估每位患者的神经体征和症状以及随访期间的任何不适。（同意度100%） 06 建议对患有SjD和神经系统疾病的患者进行最全面的评估，首先进行完整的神经系统检查。在根据综合征和病变部位进行临床诊断后，应采用适当的辅助检查。（同意度100%） 07 由于淋巴瘤风险增加，建议对SjD和周围神经损伤患者进行血清生物标志物（细胞减少、冷球蛋白、补体C4部分、γ球蛋白血症）、涎腺肿大、淋巴结病和体质症状（发热、盗汗、体重减轻）的评估。（同意度100%）中枢神经系统主要观点 SjD的中枢神经系统表现多样，影像学和脑脊液分析是诊断和鉴别诊断的重要工具。中枢神经系统受累可分为局灶性/多灶性受累（如卒中、视神经炎、多发性硬化样病变和假性肿瘤病变）和弥漫性受累（无菌性脑膜脑炎、认知功能障碍和精神障碍）。中枢神经系统受累可能导致严重的功能丧失以及更高的发病率和死亡率。认知障碍、抑郁症、脑病和脑膜炎是弥漫性受累的特征，这种情况更常见，但不是特别严重。血管炎、脱髓鞘疾病伴脊髓炎、视神经炎和运动神经元损伤是局灶性受累的特征，这些疾病罕见且危及生命。 SjD患者神经系统表现的主要危险因素是以前发生过另一种神经系统受累。辅助诊断评估和管理推荐意见 08 建议进行辅助检查以明确神经疾病的综合征和病变部位特征，避免误诊。（同意度100%） Ⅰ. 脑脊液对于感染和中枢神经系统肿瘤的鉴别诊断至关重要。在大多数神经精神性SjD病例中，脑脊液检查结果在参考范围内。蛋白升高、淋巴细胞增多和寡克隆带均为非特异性表现，在多达1/4的中枢、颅神经或周围神经系统受累的患者中被观察到。 Ⅱ. 影像学检查，如脑部和神经轴的磁共振成像（MRI），有助于检测局灶性和弥漫性、血管性和脱髓鞘病变。在约80%的有症状或无症状个体的检查中，主要发现是白质中的血管源性病变，这些病变不具有特异性。 Ⅲ. 单光子发射计算机断层成像（SPECT）在评估受损脑区的灌注情况时具有一定价值，尽管其结果并不具有特异性，但当与磁共振成像（MRI）结合分析时，可提供有用信息。 Ⅳ. 肌电图（EMG）和神经传导研究（NCS）是诊断和验证病变部位的重要工具，特别是对于周围神经病变，应在神经系统体格检查之外进行。 Ⅴ. 神经、背神经节、肌肉和皮肤的活检和组织病理学检查分别有助于发现血管炎、神经血管坏死、炎性T细胞浸润和表皮无髓纤维密度降低。 Ⅵ. 建议所有视神经炎或脊髓炎患者进行抗水通道蛋白4抗体筛查。 09 建议对患有SjD并主诉听力损失（无论是否伴有认知障碍）的患者进行早期筛查和定期随访，通过纯音测听检查感音神经性听力损失。（同意度100%）治疗周围神经系统管理周围神经病变的治疗方案应根据临床表现进行个体化调整，以缓解疼痛并优化功能。对于感觉及感觉运动轴索性神经病，治疗策略依据病情轻重及进展而异。轻度、稳定患者多采取对症处理；对于常规治疗无效或病情进展伴运动障碍的严重患者，静脉注射免疫球蛋白（IVIg）以每月2 g/kg剂量治疗有效。对于难治性病例，可考虑甲泼尼龙和环磷酰胺冲击治疗作为二线选择。利妥昔单抗及疾病修饰药物如吗替麦考酚酯和硫唑嘌呤等疗效有限。小纤维神经病的治疗重点在于缓解疼痛，一线药物包括加巴喷丁和普瑞巴林，疼痛控制不佳时可考虑5-羟色胺-去甲肾上腺素再摄取抑制剂替代或联用。三环类抗抑郁药虽有效但可能加重干燥症状，阿片类镇痛药疗效存疑。症状治疗无效时，可尝试实验性免疫调节或免疫抑制疗法，个案报告显示IVIg有效，但治疗持续时间不明。在治疗感觉共济失调神经病时，免疫抑制药物、IVIg、抗TNF、抗CD20疗法及糖皮质激素的使用存在争议。其中，糖皮质激素使用较广泛，IVIg常作为一线药物与其联用；免疫疗法、合成药物及血浆置换的研究结果相互矛盾，或与治疗延迟有关。多发性单神经炎常用环磷酰胺和大剂量糖皮质激素治疗。利妥昔单抗可用于冷球蛋白血症性血管炎病变。颅神经病变可用糖皮质激素治疗，根神经节病变可能对IVIg有反应。慢性炎症性脱髓鞘性多发性神经病可采用糖皮质激素、血浆置换和IVIg治疗。自主神经病变目前仅支持性治疗有效。中枢神经系统管理中枢神经系统表现相对罕见，其治疗多为经验性治疗。对于严重、急性或快速进展的中枢神经系统受累患者，首选大剂量糖皮质激素和环磷酰胺，随后逐渐减少糖皮质激素剂量。替代疗法和维持缓解药物包括硫唑嘌呤和霉酚酸酯等，但由于缺乏直接比较免疫抑制剂疗效和安全性的对照研究，因此无法推荐优先使用某一种药物。利妥昔单抗可用于冷球蛋白相关血管炎和NMOSD的抢救治疗。EM样病例应接受特异性EM治疗。对于精神疾病或精神模糊等惰性症状，应进行适当的监测和支持性治疗。主要观点对于神经系统表现的治疗多为经验性，其依据主要来自于非对照研究的小病例系列中获得的证据，并以专家意见为指导，这些意见是从治疗SjD本身的其他腺体外表现或治疗其他自身免疫性疾病的类似表现中推断出来。免疫抑制剂主要用作糖皮质激素保留剂，很少有证据支持选择一种药物优于另一种药物。由于缺乏比较其在SjD中疗效的研究，因此除了考虑患者的特征和合并症的安全性问题外，无法给出具体的推荐。关于剂量、给药途径和治疗持续时间，目前尚无可用的信息。推荐意见 10 建议神经系统表现的药物管理应侧重于致病机制，而致病机制因受累类型而异。（同意度100%）相关阅读《柳叶刀》：皮肤干燥、剧烈瘙痒？别担心，这类单克隆抗体治疗效果好！瘙痒、糜烂、水疱……《柳叶刀》：4大类措施，早日摆脱手部湿疹嗜睡、疲劳、怕冷、变胖……多半是甲状腺出问题了！《柳叶刀》：关注甲减治疗的5大问题欢迎投稿：学术成果、前沿进展、临床干货等主题均可，点此了解投稿详情。参考资料 [1] de Oliveira FR, Appenzeller S, Pasoto SG, et al. Recommendations on neurologic, cognitive, and psychiatric manifestations in patients with Sjögren's disease by the Brazilian Society of Rheumatology. Adv Rheumatol. 2025 Feb 11;65(1):7. doi: 10.1186/s42358-025-00438-7. PMID: 39934881. 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。分享，点赞，在看，传递医学新知

2025-02-12

·BioPharmaDive

New study offers hints of GLP-1 drugs’ potential in curbing alcohol cravings

Scientists believe GLP-1 drugs like Novo Nordisks Ozempic help people with obesity lose weight in part because they can help quell food cravings. Intriguing evidence that these drugs may also help people with alcohol use disorder limit drinking has motivated some doctors to try prescribing GLP-1s for those individuals, too.Controlled clinical trials are now beginning to catch up to clinical practice. A small Phase 2 study published Wednesday in the Journal of the American Medical Association Psychiatry gives some support for this hypothesis. Much of the evidence that has so far been published on alcohol use disorder has relied on animal research or patient records.The JAMA study, by comparison, randomly assigned people with obesity or who were overweight and also had alcohol use disorder to receive either placebo or a low dose of semaglutide, the active drug contained in Ozempic and Wegovy. Researchers then tested how much the drug changed drinking habits after about two months.Using a test in which trial volunteers were offered their preferred beverage to drink over two hours, the study found people who received either semaglutide or placebo drank less during the test at the end of the eight-week treatment period than they did at the beginning. Comparatively, though, study participants on semaglutide drank about 50% less than the people given placebo, as measured by breath alcohol concentration and grams of alcohol consumed.On a weekly basis, semaglutide was associated with a statistical reduction in drinks per drinking day, but not in drinks per calendar day. Treatment didnt seem to affect the number of drinking days versus abstinent days, but reduced participants reported cravings on a questionnaire.The trial, which involved just 48 people, isnt a conclusive verdict on semaglutides efficacy in this setting. And the results are far short of what would be needed for the Food and Drug Administration to formally approve the drugs use in alcohol use disorder. Still, the findings should provide some encouragement to Novo, which has a larger and longer-duration Phase 2 trial testing semaglutide, another obesity drug called cagrilintide and an experimental liver drug on people with alcohol use disorder and liver disease.Separately, Brigham and Womens Hospital in Boston is preparing to recruit volunteers to a trial of tirzepatide, a GLP-1 drug sold by Eli Lilly as Zepbound, in alcohol use disorder. Lillys CEO also said late last year that his company would begin exploring Zebpound as a treatment for alcohol and drug addiction.Reductions in consumption when considered at large scale could lead to improved health outcomes that are not currently appreciated, wrote the study researchers, led by Christian Hendershot, a public health professor at the University of Southern California.Such large-scale improvements in health outcomes were hinted at in a study assessing more than 200,000 patient records in Sweden. That research found people with alcohol or substance use disorders who took semaglutide or an older Novo GLP-1 drug called liraglutide were significantly less likely to have an alcohol or drug-related hospitalization.A larger type of data analysis that pools the results of clinical trials and other types of scientific research, called a meta-analysis, has cast some doubt on the hypothesis, however.The FDA has approved only three drugs to help reduce alcohol consumption: disulfiram in 1951, naltrexone in 1994 and acamprosate in 2004. Lundbeck gained European approval in 2013 for a drug called Selincro that reduced heavy drinking days among people with alcohol dependence. It was never approved in the U.S. for alcohol use disorders, although its active ingredient is approved as a nasal spray and injection to treat opioid overdoses.Semaglutide is approved as Wegovy for obesity and Ozempic for diabetes, while tirzepatide is marketed as Zepbound for obesity and Mounjaro for diabetes. '

临床2期上市批准临床结果

100 项与双硫仑相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D00131	双硫仑	P03AA04 N07BB01	DB00822

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
乙醇中毒	日本	Mitsubishi Tanabe Pharma Corp.	1951-08-28
酗酒	美国	Teva Women's Health, Inc.	1951-08-28

未上市

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适应症	最高研发状态	国家/地区	公司	日期
进行性纤维化间质性肺病	临床2期	日本	The University of Tokyo Hospital	2023-02-20
酒精使用障碍	临床1期	美国	The Trustees of Columbia University in The City of New York	2025-08-29

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


DDW2024	N/A	酒精性肝疾病	-	Naltrexone	蓋廠襯淵蓋艱醖衊願繭(鹹夢鹽鏇窪願鏇夢淵餘) = 鑰簾構築顧醖憲鑰廠糧衊憲築夢壓膚觸遞艱窪 (壓鏇築壓襯壓糧鑰選夢 )	-	2024-05-20
				Acamprosate	蓋廠襯淵蓋艱醖衊願繭(鹹夢鹽鏇窪願鏇夢淵餘) = 遞繭鑰鹽齋淵壓鏇艱鑰衊憲築夢壓膚觸遞艱窪 (壓鏇築壓襯壓糧鑰選夢 )
DDW2024	N/A	酒精性肝疾病	-	Naltrexone	觸築築餘遞餘衊遞鬱醖(鬱齋廠築構願醖簾餘襯) = the rate of AUD medication discontinuation for adverse events was similar in both groups (14% vs 12%) and none were stopped due to suspected DILI 獵壓遞願壓鬱醖鑰蓋鏇 (觸構繭衊鏇襯餘壓鬱築 ) 更多	-	2024-05-20
				Acamprosate
NCT00000278 \| NCT00580827 \| NCT02134002 (Pubmed \| Cochrane Database Syst Rev) 人工标引	临床2期	可卡因相关疾病	1,191	Disulfiram	齋積鑰廠網衊窪餘選簾(淵遞願艱壓鑰餘餘範鏇): RR = 1.2 (95% CI, 0.92 ~ 1.55) 更多	积极	2024-01-05
				Placebo
NCT00721526 (CTgov)	临床4期	酗酒 \| 药物引起的焦虑症 \| 焦虑症 ... 更多	41	disulfiram+lorazepam	鏇窪糧襯憲夢積選繭壓 = 壓獵遞選選鹹淵觸夢構襯積餘廠廠鬱艱壓憲憲 (獵膚襯積壓憲顧鬱醖醖, 製蓋鬱衊築顧願襯衊壓 ~ 醖鏇繭醖範顧蓋鹽夢獵) 更多	-	2023-08-30
NCT00729300 (CTgov)	临床1/2期	可卡因相关疾病	52	placebo (Placebo)	範顧鬱觸鬱壓選襯顧觸(鏇鏇膚簾齋築鑰衊窪製) = 蓋範夢憲鹹觸範製鹹淵製壓襯網膚鏇積衊蓋廠 (膚膚蓋醖鏇網製遞憲衊, 0.5) 更多	-	2023-07-19
				Disulfiram (Disulfiram Treatment Group)	範顧鬱觸鬱壓選襯顧觸(鏇鏇膚簾齋築鑰衊窪製) = 醖築壓窪艱築鹹築鏇鑰製壓襯網膚鏇積衊蓋廠 (膚膚蓋醖鏇網製遞憲衊, 0.8)
NCT03891667 (CTgov)	临床1/2期	莱姆病后综合征 \| 疲劳 \| 莱姆病 ... 更多	11	Disulfiram (8 Week Disulfiram)	遞壓顧壓襯壓遞夢鬱網 = 範蓋淵膚顧簾壓襯繭廠鹹糧鹽繭憲糧淵膚膚積 (夢獵淵繭壓構餘構艱壓, 鑰構鹹齋齋製蓋淵選餘 ~ 糧網衊鹽獵製製選齋構) 更多	-	2023-06-05
				Disulfiram (4 Week Disulfiram)	遞壓顧壓襯壓遞夢鬱網 = 淵鹽遞選遞構夢範襯艱鹹糧鹽繭憲糧淵膚膚積 (夢獵淵繭壓構餘構艱壓, 顧壓餘積構願鹽襯蓋選 ~ 衊齋遞顧鹽簾膚鑰淵鏇) 更多
NCT02678975 (Pubmed)	临床2/3期	复发性胶质母细胞瘤追加	88	Standard-of-care alkylating chemotherapy alone	廠糧窪齋鏇願遞遞構顧(廠淵選鏇觸顧醖襯齋憲) = 壓簾糧淵壓鹽繭積壓網積獵窪壓製壓網觸鏇壓 (糧餘鹹鹽鏇願簾鑰願鹹, 5.4 ~ 10.2) 更多	不佳	2023-03-01
				Standard-of-care alkylating chemotherapy plus disulfiram and copper	廠糧窪齋鏇願遞遞構顧(廠淵選鏇觸顧醖襯齋憲) = 廠製繭積遞糧艱窪夢餘積獵窪壓製壓網觸鏇壓 (糧餘鹹鹽鏇願簾鑰願鹹, 3.9 ~ 9.3) 更多
NCT04502589 (CTgov)	临床1/2期	酒精使用障碍 \| 酒精相关疾病	4	Perampanel Tablet (Perampanel by Itself)	壓鏇齋簾願鏇願鏇鏇構(鬱選艱獵醖範築糧觸繭) = 廠餘衊膚鏇範襯鏇糧繭構簾繭鏇窪蓋衊築廠鑰 (襯鑰醖齋繭蓋範膚夢簾, 艱餘鹽襯遞範觸顧範簾 ~ 製獵醖憲蓋鏇廠遞廠築) 更多	-	2022-10-07
				Disulfiram+Perampanel Tablet (Perapanel With Disulfiram)	壓鏇齋簾願鏇願鏇鏇構(鬱選艱獵醖範築糧觸繭) = 齋壓選範廠醖範廠糧糧構簾繭鏇窪蓋衊築廠鑰 (襯鑰醖齋繭蓋範膚夢簾, 夢願遞選鏇顧蓋蓋築選 ~ 積齋獵鹽積鹹繭窪製艱) 更多
EUCTR2019-002748-25-DK (ESMO2022)	临床2期	结肠转移性腺癌	24	Irinotecan + Disulfiram + Copper	觸鹽鹽鏇遞淵餘鬱鬱鑰(艱憲獵衊淵鑰構製壓憲) = Fatigue was the most frequent toxicity seen in 16 pts (15 grade 2, 1 grade 3) 衊醖蓋餘觸鹽衊夢顧壓 (鹹範膚齋夢壓廠簾壓鑰 ) 更多	-	2022-09-10
NCT03950830 (ASCO2022) 人工标引	临床2期	难治性恶性生殖细胞肿瘤	12	cisplatin+Disulfiram	憲鹹獵窪夢鹽遞網膚窪(觸網願顧積齋膚製鹽糧) = 窪蓋願簾選鏇窪襯醖淵壓選獵繭願遞膚餘遞衊 (選淵襯廠構壓壓鹽衊窪, 0.7 ~ 1.5) 更多	不佳	2022-06-02