Determining Optimal Treatment Sequences in Anxious Depression (DOTS-AD)
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 84
- 试验地点
- 1
- 主要终点
- Change from Baseline in Hamilton Anxiety Rating Scale (HAM-A) total score
研究概览
简要总结
Acute, double-blind, adaptively randomized treatment with duloxetine or escitalopram, followed by double-blind, randomized adjunctive treatment with clonazepam or pregabalin for persistent symptoms.
详细描述
The study will consist of 2 phases (Figure 1). Eighty-four adults will be enrolled in Phase 1 and will be adaptively randomized (initially 1:1) to acute, double-blind treatment with escitalopram or duloxetine for 11 weeks. Remission status will be determined at week 10. Remitting patients (CGI-S ≤2) will resume treatment as usual, which may consist of outpatient referral. Non-remitting patients (CGI-S ≥3), will continue into Phase 2 and will be randomized to adjunctive clonazepam or pregabalin for 8 weeks. Twenty adults treated with escitalopram (or its racemic equivalent, citalopram) or duloxetine for ≥6 weeks (at screening) will be enrolled into Phase 2 and will be randomized to receive adjunctive clonazepam or pregabalin for 8 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written, informed consent.
- •Patients must be fluent in the English.
- •18 to 50 years of age, inclusive, at Visit
- •Patients must meet DSM-5 criteria for generalized, social and/or separation anxiety disorder and/or panic disorder, confirmed by the MINI.99 Patients may also meet criteria for persistent depressive disorder or major depressive disorder however, these may not be the primary focus of treatment.
- •HAM-A score ≥20 at Visits 1 and
- •Clinical Global Impressions- Severity (CGI-S) score ≥4 at Visits 1 and
- •No clinically significant abnormalities on physical examination and EKG.
- •Negative pregnancy test at Visit 1 in females.
- •Negative urine drug screen at Visit
- •Sexually active patients must practice a reliable method of contraception (Section 15.0) that will continue for the duration of the study and for a minimum of 30 days following the end of study participation. Reliable methods of contraception are defined below; other forms of contraceptives (pharmacological and/or non-pharmacological) are not accepted:
- •Surgical sterilization
- •Oral contraceptives (e.g. estrogren-progestin combination or progestin)
- •Transdermally-delivered contraceptives (e.g., Ortho-Evra), depot injections (e.g., Depo-Provera)
- •Vaginal contraceptive ring (e.g., NuvaRing), contraceptive implants (e.g., Implanon, Norplant II/Jadelle)
- •An intrauterine device
- •Diaphragm plus condom.
- •For patients directly enrolling into Phase 2: treatment with escitalopram (or its racemic equivalent citalopram) or duloxetine for ≥6 weeks, at time of screening.
排除标准
- •DSM-5 diagnosis other than generalized anxiety, social anxiety, separation anxiety or panic disorder(s) that is the primary focus of treatment.
- •A history of intellectual disability.
- •Suicide risk as determined by either: (1) any suicide attempt within the past 6 months and/or (2) significant risk at Visit 1 (Screening) or Visit 2 (Baseline), as judged by the Investigator.
- •Allergy, intolerance, non-response or hypersensitivity to escitalopram, duloxetine, pregabalin or clonazepam.
- •Subjects taking other medications that require a taper or washout of more than 5 days.
- •Patients who have initiated/terminated psychotherapy/behavior therapy within 1 month before Visit 2 (Baseline) will be excluded; if the patient is engaged in psychotherapy, it must have been stable for 1 month prior to baseline.
- •A clinically-significant medical illness.
- •QTc >450 in males or >460 in females (prolonged QTc based on American Heart Association recommendations for Standardization and Interpretation of the EKG100
- •Alcohol or substance use disorder within 6 months of baseline (nicotine use is permitted).
- •Positive urine pregnancy test/pregnancy or breast feeding.
- •A positive urine drug screen.
- •Patients who are unable to swallow capsules.
研究组 & 干预措施
Escitalopram
Adaptively randomized, double-blind treatment with escitalopram for 11 weeks in Phase 1. Non-remitting patients will be randomized in Phase 2 to adjunctive clonazepam or pregabalin for 8 weeks. Additionally, adults who are already treated with escitalopram or citalopram for at least 6 weeks prior to screening, may enter Phase 2 and be randomized to adjunctive clonazepam or pregabalin for 8 weeks.
干预措施: Escitalopram (Drug)
Duloxetine
Adaptively randomized, double-blind treatment with duloxetine for 11 weeks in Phase 1. Non-remitting patients will be randomized in Phase 2 to adjunctive clonazepam or pregabalin for 8 weeks. Additionally, adults who are already treated with duloxetine for at least 6 weeks prior to screening, may enter Phase 2 and be randomized to adjunctive clonazepam or pregabalin for 8 weeks.
干预措施: Duloxetine (Drug)
结局指标
主要结局
Change from Baseline in Hamilton Anxiety Rating Scale (HAM-A) total score
时间窗: Week 2 to 20
The HAM-A rating scale is a test of 14 items measuring the severity of anxiety symptoms. Each item is rated on a 5-point ordinal scale, ranging from 0 (not present) to 4 (severe). Total scores range from 0 to 56. A lower score is favorable.
Change from Baseline in the Clinical Global Impression of Severity (CGI-S)
时间窗: Week 2 to 20
CGI-S is a seven point scale where 1=Normal and 7=Among the most extremely ill patients.
次要结局
未报告次要终点
研究者
Jeffrey Strawn, MD
Associate Professor of Psychiatry & Pediatrics, Director, Anxiety Disorders Research Program
University of Cincinnati