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

NCT04245748 | Recruiting Phase 4 FDA Drug

• 1 other identifier: Strawn DOTS-AD
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

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.

Conditions

Anxious Depression; Depression

Keywords

Anxious Depression

Outcome Measures

Primary Outcomes (2)

• Change from Baseline in Hamilton Anxiety Rating Scale (HAM-A) total score

  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.

  Week 2 to 20

• Change from Baseline in the Clinical Global Impression of Severity (CGI-S)

  CGI-S is a seven point scale where 1=Normal and 7=Among the most extremely ill patients.

  Week 2 to 20

Study Arms (2)

Escitalopram

ACTIVE COMPARATOR

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.

Drug: Escitalopram

Duloxetine

ACTIVE COMPARATOR

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.

Drug: Duloxetine

Interventions

Escitalopram 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.

Also known as: Lexapro

Escitalopram

Duloxetine 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.

Also known as: Cymbalta

Duloxetine

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Written, informed consent.
• Patients must be fluent in the English.
• 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:
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Cincinnati: lead

Study Sites (1)

University of Cincinnati, Department of Psychiatry & Behavioral Neuroscience

Cincinnati, Ohio, 45219, United States

RECRUITING

MeSH Terms

Conditions

Depression

Interventions

Escitalopram; Duloxetine Hydrochloride

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Thiophenes; Sulfur Compounds; Heterocyclic Compounds, 1-Ring

Study Officials

• Jeffrey R Strawn, MD, FAACAP

  University of Cincinnati

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Heidi K Schroeder, BS

CONTACT

(513) 558-4422; heysehk@uc.edu

Zoe N Neptune, BS

CONTACT

(513) 558-2866; neptunza@uc.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Psychiatry & Pediatrics, Director, Anxiety Disorders Research Program

Study Record Dates

• First Submitted: January 27, 2020
• First Posted: January 29, 2020
• Study Start: March 1, 2020
• Primary Completion: July 30, 2025
• Study Completion: December 31, 2025
• Last Updated: August 29, 2024

Record last verified: 2024-08

Locations

US (1)