Clinical trial NCT04245748: Determining Optimal Treatment Sequences in Anxious Depression (DOTS-AD)
Official title: Determining Optimal Treatment Sequences in Anxious Depression (DOTS-AD)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Anxious Depression
Depression
Keywords: Anxious Depression
Lead sponsor: University of Cincinnati
Sponsor class: OTHER
First posted: 2020-01-29
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Acute, double-blind, adaptively randomized treatment with duloxetine or escitalopram, followed by double-blind, randomized adjunctive treatment with clonazepam or pregabalin for persistent symptoms.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Written, informed consent.
* Patients must be fluent in the English.
* 18 to 50 years of age, inclusive, at Visit 1.
* 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 2.
* Clinical Global Impressions- Severity (CGI-S) score ≥4 at Visits 1 and 2.
* No clinically significant abnormalities on physical examination and EKG.
* Negative pregnancy test at Visit 1 in females.
* Negative urine drug screen at Visit 1.
* 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:

  1. Surgical sterilization
  2. Oral contraceptives (e.g. estrogren-progestin combination or progestin)
  3. Transdermally-delivered contraceptives (e.g., Ortho-Evra), depot injections (e.g., Depo-Provera)
  4. Vaginal contraceptive ring (e.g., NuvaRing), contraceptive implants (e.g., Implanon, Norplant II/Jadelle)
  5. An intrauterine device
  6. 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Change from Baseline in Hamilton Anxiety Rating Scale (HAM-A) total score
timeFrame: Week 2 to 20
measure: Change from Baseline in the Clinical Global Impression of Severity (CGI-S)
timeFrame: Week 2 to 20
Secondary outcomes:
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: University of Cincinnati, Department of Psychiatry & Behavioral Neuroscience
state: Ohio
Study officials:
affiliation: University of Cincinnati
name: Jeffrey R Strawn, MD, FAACAP
role: PRINCIPAL_INVESTIGATOR
References: