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

Depression Clinical Trial

— DOTS-AD  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04245748
• Other study ID #: Strawn DOTS-AD
• Status: Recruiting
• Phase: Phase 4
• Start date: March 1, 2020
• Est. completion date: December 31, 2024

Study information

• Verified date: September 2023
• Source: University of Cincinnati
• Contact: Heidi K Schroeder, BS
• Phone: (513) 558-4422
• Email: heysehk[@]uc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 84
• Est. completion date: December 31, 2024
• Est. primary completion date: July 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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.

Related Conditions & MeSH terms

• Anxious Depression
• Depression
• Depressive Disorder

Intervention

Drug:
• 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.
• 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.

Locations

Country	Name	City	State
United States	University of Cincinnati, Department of Psychiatry & Behavioral Neuroscience	Cincinnati	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
University of Cincinnati

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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