Guanfacine to reduce relapse risk in women with alcohol use disorder (AUD)

胍法辛可降低女性酒精使用障碍 (AUD) 复发风险

• 批准号: 9091802
• 负责人: Helen Cecilia Fox
• 金额: $ 18.78万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-01-14 至 2018-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9091802
• 关键词: Abstinence; Adherence; Adrenergic Agents; Adrenergic Agonists; Adrenergic Receptor; Adverse effects; Alcohol abuse; Alcohol consumption; Anxiety; Appointment; Arousal; Attenuated; Behavior; Behavior Therapy; Biological; Biological Markers; Breathalyzer Tests; CRH gene; Characteristics; Clinical; Cognitive; Collection; Complex; Data; Development; Diagnosis; Disadvantaged; Disease; Dose; Double-Blind Method; Drug abuse; Effectiveness; Emotional; Exposure to; FDA approved; Gender; Glucuronides; Glutamates; Guanfacine; Health; Imagery; Impulsivity; Interview; Labor Forces; Laboratories; Laboratory Study; Lead; Link; Measures; Medical; Moods; Motivation; Norepinephrine; Outcome; Outcome Measure; Outpatients; Participant; Patient Self-Report; Pattern; Pharmaceutical Preparations; Pharmacology; Phase II Clinical Trials; Placebo Control; Placebos; Population; Process; Protocols documentation; Publishing; Randomized; Randomized Clinical Trials; Recovery; Recruitment Activity; Regulation; Relapse; Research; Rewards; Risk Factors; Safety; Socialization; Specificity; Stress; Symptoms; System; Time; Toxicology; Treatment outcome; Up-Regulation; Urine; Variant; Withdrawal; Withdrawal Symptom; Woman; alcohol abstinence; alcohol craving; alcohol effect; alcohol seeking behavior; alcohol use disorder; attenuation; biological adaptation to stress; cognitive control; cognitive enhancement; cognitive reappraisal; comparative; contingency management; craving; drinking; efficacy study; emotion regulation; experimental study; follow-up; improved; men; negative mood; pilot trial; postsynaptic; presynaptic; prevent; primary outcome; problem drinker; public health relevance; receptor; relapse risk; secondary outcome; sex; socioeconomics; stress reactivity; therapy development; treatment adherence; treatment trial

 DESCRIPTION (provided by applicant): Approximately 5.7 million women in the US meet criteria alcohol use disorder (AUD). While this figure remains significantly lower than men, the traditional gender gap is rapidly converging as a result of sharp elevations in women drinking patterns due, in part, to socioeconomic gains within the labor force. As gender- specific risk factors for AUD place women at a considerable disadvantage in terms of clinical health outcomes, this sharp increase in alcohol consumption urgently necessitates the development of interventions that have been specifically tailored to women. In view of this, preliminary data from our laboratory has shown that the alpha2 adrenergic agonist, guanfacine, attenuates the negative reinforcing effects of alcohol and enhances cognitive regulation in the face of stress, preferentially in early abstinent women compared with men. We suggest that this may be due to gender-specific variation in sympathetic sensitivity. Thus, we propose a double blind, placebo-controlled, 10-week randomized clinical trial to examine the preliminary effects of guanfacine extended release (GXR, 3mgs/daily) in 60 women with AUD. A parallel 2-day experimental study using a stress versus neutral imagery exposure paradigm will also be conducted following 4 weeks of treatment (when at full dose), to examine the stress-related subjective and biological markers of change underpinning guanfacine's efficacy. Sixty women with AUD will be recruited to take part in the 10-week outpatient trial for GXR (3mgs/daily) versus placebo (PLA). This will include twice weekly appointments comprising medical management and contingency management protocols, collection of urine, breathalyzer screens, and vitals. Measures of craving and mood will also be assessed. Participants who maintain abstinence for 4 weeks will take part in 2 laboratory challenge sessions, where they will be exposed to a personal stress versus relaxing imagery condition, 1 condition per day, in a randomized order. Craving, anxiety, mood, cognitive control, HRBP, and biological stress system markers will be assessed at baseline, following imagery and at various recovery time- points. A follow-up interview will be conducted 30 days following outpatient completion. In view of prior research, we anticipate that GXR will be safe and well tolerated in women with AUD (H1); lead to greater abstinence and treatment adherence compared with the PLA group (primary outcome measures) (H2a) as well as greater attenuation of withdrawal symptoms and improved regulatory function (secondary outcome measures) both during outpatient treatment (H2b) and following stress exposure in the laboratory (H3a). We also anticipate that GXR-related changes to stress response in the laboratory will predict improved primary alcohol use outcomes (H3b). Findings will help to elucidate unique stress-system mechanisms which support attenuation of drinking in women with AUD prior to further assessment in larger randomized clinical trials. This is of paramount importance to developing medications that are integral to the health and well-being of an increasingly vulnerable sub-population of drinkers.

 描述（由适用提供）：美国约有570万妇女符合酒精使用障碍（AUD）。尽管这一数字仍然大大低于男性，但由于劳动力内的社会经济收益，传统的性别差距迅速融合了妇女饮酒方式的急剧升高。由于在临床健康状况方面，AUD的性别特异性风险因素使妇女陷入了巨大的灾难，因此急需饮酒的急剧增加是为了为女性而定制的干预措施的发展。鉴于此，来自 我们的实验室表明，Alpha2肾上腺素激动剂鸟法汀会减弱酒精的负面增强作用，并在面对压力下增强认知调节，而与男性相比，最好在早期戒酒中。我们建议这可能是由于性别特定的交感神经敏感性变化所致。这是我们提出了一个双盲，安慰剂对照，为期10周的随机临床试验，以检查60名aud女性的鸟法汀延伸释放（GXR，3MGS/每日）的初步影响。使用应力与中性成像暴露范式进行的2天平行的实验研究也将在4周的治疗后（在全剂量时）进行，以检查与压力相关的主观和生物学标志物，而变化的变化是基于鸟甲酸的效率的基础。将招募60名具有AUD的妇女参加为期10周的GXR（每天3mgs/Daill）与安慰剂（PLA）的门诊试验。这将包括每周两次完成医疗管理和应急管理协议，尿液收集，Brathalyzer屏幕和生命力。渴望和情绪的度量也将得到评估。维持禁欲4周的参与者将参加2次实验室挑战会议，在那里他们将以随机的顺序暴露于每天1条状态的个人压力与放松图像状况。渴望，焦虑，情绪，认知控制，HRBP和生物压力系统标志物将在基线，图像和各种恢复时间点进行评估。门诊完成后30天将进行后续采访。鉴于先前的研究，我们预计GXR的AUD女性（H1）将是安全且耐受性的；与PLA组（主要结局指标）（H2A）以及在门诊治疗（H2B）和实验室（H3A）的压力暴露之后，导致更大的禁欲和治疗依从性（H2A）（H2A）（H2A）（H2A）（H2A）（H2A）以及改善的调节功能（次要结局指标）。我们还预计，实验室中与GXR相关的压力反应的变化将预测主要的一级饮酒结果（H3B）。调查结果将有助于阐明独特的应力系统机制，这些机制支持在大型随机临床试验中进一步评估的有AUD的女性饮酒的衰减。这对于开发对饮酒者越来越脆弱的亚人群的健康和福祉不可或缺的药物至关重要。