Determining Optimal Treatment Sequences in Anxious Depression (DOTS-AD)

NCT ID: NCT04245748

Last Updated: 2024-08-29

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 84 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-03-01
• Study Completion Date: 2025-12-31

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.

Conditions

Anxious Depression; Depression

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Escitalopram

Intervention Type: DRUG

Escitalopram, a SSRI, commercially known as LexaproTM, is commonly prescribed for anxiety disorders and is FDA-approved for acute and maintenance treatment of MDD and GAD.

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.

Group Type: ACTIVE_COMPARATOR

Duloxetine

Intervention Type: DRUG

Duloxetine, a SNRI, commercially known as CymbaltaTM, is FDA-approved for the treatment of GAD, MDD, diabetic peripheral neuropathic pain, fibromyalgia, and chronic musculoskeletal pain in adults.

Interventions

Escitalopram

Escitalopram, a SSRI, commercially known as LexaproTM, is commonly prescribed for anxiety disorders and is FDA-approved for acute and maintenance treatment of MDD and GAD.

Intervention Type: DRUG

Duloxetine

Duloxetine, a SNRI, commercially known as CymbaltaTM, is FDA-approved for the treatment of GAD, MDD, diabetic peripheral neuropathic pain, fibromyalgia, and chronic musculoskeletal pain in adults.

Intervention Type: DRUG

Other Intervention Names

Lexapro; Cymbalta

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Cincinnati

OTHER

Sponsor Role: lead

Responsible Party

Jeffrey Strawn, MD

Associate Professor of Psychiatry & Pediatrics, Director, Anxiety Disorders Research Program

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jeffrey R Strawn, MD, FAACAP

Role: PRINCIPAL_INVESTIGATOR

University of Cincinnati

Locations

University of Cincinnati, Department of Psychiatry & Behavioral Neuroscience

Cincinnati, Ohio, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Heidi K Schroeder, BS

Role: CONTACT

heysehk@uc.edu

(513) 558-4422

Zoe N Neptune, BS

Role: CONTACT

neptunza@uc.edu

(513) 558-2866

Facility Contacts

Jeffrey R Strawn, MD, FAACAP

Role: primary

strawnjr@ucmail.uc.edu

513-558-4315

Heidi K Schroeder, BS

Role: backup

heysehk@uc.edu

(513) 558-4422

Other Identifiers

Strawn DOTS-AD

Identifier Type: -

Identifier Source: org_study_id