Department of Psychosomatic Medicine and Psychotherapy, University Hospital Erlangen, Schwabachanlage 6, 91054, Erlangen, Germany.
Center for Clinical Studies, Krankenhausstraße 12, 91054, Erlangen, Germany.
BMC Psychiatry. 2018 Apr 10;18(1):93. doi: 10.1186/s12888-018-1683-1.
There is a need for novel treatment approaches in anorexia nervosa (AN). While there is broad knowledge with regard to altered appetite regulation and neuropsychological deficits in AN patients on the one hand, and the effects of estrogen replacement upon neuropsychological performance in healthy subjects on the other, up to now, no study has implemented estrogen replacement in AN patients, in order to examine its effects upon AN-associated and general psychopathology, neuropsychological performance and concentrations of peptide components of the hypothalamus-pituitary-adrenal (HPA) axis and within appetite-regulating circuits.
This is a randomized placebo-controlled clinical trial on the effects of a 10-week oral estrogen replacement (combination of ethinyl estradiol 0.03 mg and dienogest 2 mg) in adult female AN patients. The primary target is the assessment of the impact of sex hormone replacement upon neuropsychological performance by means of a neuropsychological test battery consisting of a test for verbal intelligence, the Trail making test A and B, a Go/No-go paradigm with food cues and the Wisconsin Card Sorting Test. Secondary targets include a) the examination of safety and tolerability (as mirrored by the number of adverse events), b) assessments of the impact upon eating disorder-specific psychopathology by means of the Eating Disorder Examination Questionnaire (EDE-Q) and the Eating Disorder Inventory-2 (EDI-2), c) the influence upon anxiety using the State-Trait-Anxiety Inventory (STAI), d) assessments of plasma cortisol levels during a dexamethasone-suppression test and appetite-regulating plasma peptides (ghrelin, leptin, insulin, glucose) during an oral glucose tolerance test and, e) a possible impact upon the prescription of antidepressants.
This is the first study of its kind. There are no evidence-based psychopharmacological options for the treatment of AN. Thus, the results of this clinical trial may have a relevant impact on future treatment regimens. Novel approaches are necessary to improve rates of AN symptom remission and increase the rapidity of treatment response. Identifying the underlying biological (e.g. neuroendocrinological) factors that maintain AN or may predict patient treatment response represent critical future research directions. Continued efforts to incorporate novel pharmacological aspects into treatments will increase access to evidence-based care and help reduce the burden of AN.
European Clinical Trials Database, EudraCT number 2015-004184-36, registered November 2015; ClinicalTrials.gov Identifier: NCT03172533 , retrospectively registered May 2017.
厌食症（AN）需要新的治疗方法。一方面，人们广泛了解 AN 患者的食欲调节改变和神经心理学缺陷，另一方面，人们也了解雌激素替代对健康受试者神经心理表现的影响，但迄今为止，尚无研究在 AN 患者中实施雌激素替代治疗，以研究其对 AN 相关和一般精神病理学、神经心理表现以及下丘脑-垂体-肾上腺（HPA）轴肽成分和食欲调节回路中的浓度的影响。
这是一项关于口服雌激素替代（结合乙炔雌二醇 0.03 毫克和地诺孕素 2 毫克）对成年女性 AN 患者 10 周影响的随机安慰剂对照临床试验。主要目标是通过使用由言语智力测试、追踪测试 A 和 B、食物线索的 Go/No-go 范式和威斯康星卡片分类测试组成的神经心理测试套件，评估性激素替代对神经心理表现的影响。次要目标包括：a）安全性和耐受性评估（反映在不良事件的数量上），b）通过饮食失调检查表问卷（EDE-Q）和饮食失调清单-2（EDI-2）评估对饮食失调特异性精神病理学的影响，c）使用状态-特质焦虑量表（STAI）评估焦虑的影响，d）评估地塞米松抑制试验期间的血浆皮质醇水平和口服葡萄糖耐量试验期间的食欲调节肽（ghrelin、瘦素、胰岛素、血糖），e）可能对抗抑郁药的处方产生影响。
这是此类研究中的首例。目前，AN 的治疗尚无基于证据的精神药理学选择。因此，这项临床试验的结果可能对未来的治疗方案有重要影响。需要新的方法来提高 AN 症状缓解率并加快治疗反应速度。确定维持 AN 的潜在生物学（例如神经内分泌学）因素或可能预测患者治疗反应的因素，是未来研究的关键方向。继续努力将新的药理学方面纳入治疗将增加获得基于证据的治疗的机会，并有助于减轻 AN 的负担。
欧洲临床试验数据库，EudraCT 编号 2015-004184-36，2015 年 11 月注册；ClinicalTrials.gov 标识符：NCT03172533，2017 年 5 月回顾性注册。
