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Vulvar vestibulitis trial: Desipramine-Lidocaine

外阴前庭炎试验：地昔帕明-利多卡因

基本信息

批准号：
7114893
负责人：
DAVID Charles FOSTER
金额：
$ 24.22万
依托单位：
UNIVERSITY OF ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-08-01 至 2007-07-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Studies are proposed for the subtype of vulvodynia known as vulvar vestibulitis. The first major aim of this application is to conduct a randomized, placebo-controlled, double-blinded clinical trial to study the clinical efficacy of four medical regimens: topical lidocaine, oral desipramine, topical lidocaine combined with oral desipramine and placebo. The efficacy of standard treatments for vulvar vestibulitis proven by randomized, placebo-controlled, blinded clinical trials has not been assessed. The tricyclic class of antidepressants, represented by desipramine, have gained empiric acceptance for the treatment of vulvar vestibulitis, although favorable therapeutic results have been reported by only a few retrospective studies or uncontrolled clinical trials. Although the precise mechanism of action remains undefined for tricyclic antidepressants, a "central" action through the dorsal horn and brain stem has been suggested. In contrast to oral desipramine, the long-term, topical application of lidocaine may act through a "local" mechanism. This randomized, placebo-controlled, double-blinded clinical trial is designed to determine whether "local" or "centrally-acting" treatments alone, or in combination are efficacious in treating vulvar vestibulitis. Outcome measures of success will include reduced overall pain, reduced pain to touch, reduced pain to standardized mechanical stimuli, increased pain-free intercourse, improved sexual function, improved quality-of-life as measured by psychometric tests, and adherence to active drug regimens. The second major aim of this application is to study the relationship among genetic polymorphisms of the IL-1 Receptor Antagonist locus, tissue levels of pro-inflammatory cytokines, and response to treatment of vulvar vestibulitis. Pro-inflammatory cytokines, such as interleukin-I beta (IL-1 beta) and tumor necrosis factor alpha (TNF-alpha), are secreted from a local cellular source and accumulate above normal levels in the region of the hymeneal ring. Recent genetic analysis finds a 53% homozygosity for allele 2 IL-1 Receptor Antagonist (IL-1 RA*2) in cases of vulvar vestibulitis, in contrast to 8.5% homozygosity in asymptomatic women. Furthermore, the IL-1 RA*2 allele has been linked to increased production of IL-1 beta in vitro. In our second aim, we will determine whether these in vitro results can be extrapolated to clinical cases of vulvar vestibulitis. Using samples from our clinical trial, we will assess the relationship between homozygosity for IL-1 RA*2, tissue levels of IL-1 beta, and TNF-alpha, and response to treatment. In summary, this project will allow us to answer several important questions about vulvar vestibulitis. Is medical treatment effective? Is centrally-acting or locally-acting treatment equally effective or is one superior to the other? Is there any benefit from combined local and systemic treatments? And finally, do genetic characteristics and tissue cytokine concentrations influence treatment response?

描述（由申请人提供）：提出外阴痛亚型外阴前庭炎的研究。本申请的第一个主要目的是进行随机、安慰剂对照、双盲临床试验，研究外用利多卡因、口服地西帕明、外用利多卡因联合口服地西帕明和安慰剂四种治疗方案的临床疗效。随机、安慰剂对照、盲法临床试验证明外阴前庭炎标准治疗的疗效尚未得到评估。以地西帕明为代表的三环类抗抑郁药已被经验接受用于治疗外阴前庭炎，尽管只有少数回顾性研究或非对照临床试验报道了良好的治疗效果。尽管三环类抗抑郁药的确切作用机制尚不明确，但已经提出了一种通过背角和脑干的“中枢”作用。与口服地西帕明相反，长期局部应用利多卡因可能通过“局部”机制起作用。这项随机、安慰剂对照、双盲临床试验旨在确定“局部”或“集中”治疗单独或联合治疗外阴前庭炎是否有效。成功的结果衡量标准包括整体疼痛减轻，触摸疼痛减轻，标准化机械刺激疼痛减轻，无痛性交增加，性功能改善，心理测试测量的生活质量改善，以及坚持积极的药物治疗方案。本应用程序的第二个主要目的是研究IL-1受体拮抗剂位点的遗传多态性、促炎细胞因子的组织水平和外阴前庭炎治疗反应之间的关系。促炎细胞因子，如白细胞介素-1 β (IL-1 β)和肿瘤坏死因子α (tnf - α)，由局部细胞源分泌，并在处女膜环区域积累高于正常水平。最近的遗传分析发现，外阴前庭炎患者的等位基因2 IL-1受体拮抗剂（IL-1 RA*2）的纯合子率为53%，而无症状女性的纯合子率为8.5%。此外，IL-1 RA*2等位基因与体外IL-1 β的产生增加有关。在我们的第二个目标中，我们将确定这些体外结果是否可以外推到外阴前庭炎的临床病例。使用我们临床试验的样本，我们将评估IL-1 RA*2的纯合性、IL-1 β和tnf - α的组织水平以及对治疗的反应之间的关系。总之，这个项目将使我们能够回答关于外阴前庭炎的几个重要问题。药物治疗有效吗？集中治疗和局部治疗是否同样有效，或者孰优孰劣？局部和全身联合治疗有什么好处吗？最后，遗传特征和组织细胞因子浓度是否影响治疗反应？