Contact: Developing New Clinical Management Strategies

NCT03812588 | Completed Phase 4 Results FDA Drug

• 1 other identifier: 7738
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this study is to develop new methods of administering antidepressant medications that will result in improved drug/placebo separation in randomized controlled trials (RCTs) for Major Depressive Disorder (MDD) and enhanced medication response in open clinical treatment. The highly intensive, weekly visit schedule followed in most antidepressant RCTs radically differs from how antidepressant medications are prescribed in standard clinical practice and is believed to be a major reason why the majority of studies submitted to the Food and Drug Administration (FDA) fail to show a significant difference between medication and placebo. Moreover, a "one size fits all" approach to psychopharmacologic management (i.e., weekly visits for all patients) does not take into account differences between patients that may predispose some individuals to respond positively to frequent follow-up visits, while others may respond negatively or not at all. Clinic visits comprise multiple components that may be therapeutic for depression, including activating patients' behavior, exposing them to medical procedures, permitting social interactions with research staff, and providing supportive meetings with clinicians. Two independent meta-analyses have associated more frequent study visits with increased antidepressant and placebo response as well as decreased separation between medication and placebo. Despite the high costs and potential disadvantages of weekly follow-up visits for patients receiving antidepressant medication, this clinical management strategy has not been studied prospectively to date. It is unknown whether weekly follow-up visits are needed to ensure treatment compliance and patient safety in clinical trials and to what degree contacts with clinicians influence medication and placebo response.

Conditions

Major Depressive Disorder

Outcome Measures

Primary Outcomes (1)

• Change From Baseline Hamilton Rating Scale for Depression 24-Item Scale to Study Completion (8 Weeks)

  Scale for depressive symptoms administered by trained rater. The Hamilton is the standard measure of depression severity for clinical trials of antidepressants and was chosen as the primary outcome measure over other depression rating scales to ensure compatibility of study results with our meta-analyses and ongoing studies of expectancy. The scoring is based on the first 24 items of the Hamilton. Sum of the scores of the first 24 items (range from 0 to 74): 0-7 = NORMAL 8-13 = Mild Depression 14-18 = Moderate Depression 19-22 = Severe Depression \>=23 = Very Severe Depression

  Up to 8 Weeks

Secondary Outcomes (1)

• Change From Baseline Hamilton Anxiety Rating Scale 14-item Scale

  Up to 8 Weeks

Other Outcomes (1)

• Change From Baseline Clinical Global Impressions

  Up to 8 Weeks

Study Arms (4)

Clinical Frequency Management: Placebo

PLACEBO COMPARATOR

Study visits monthly (Week 0, 4, and 8), with phone visits every other week (Week 2 and 6). Double-blind, placebo-controlled treatment with escitalopram 10mg/day, raised to 20mg/day, if non-responders at week 4. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits.

Drug: Placebo

Research Frequency Management: Placebo

PLACEBO COMPARATOR

Weekly study visits, treatment with double-blind, placebo controlled escitalopram 10 mg/day, raised to 20mg/day at week 4 if non-responders. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits.

Drug: Placebo

Clinical Frequency Management: Escitalopram

ACTIVE COMPARATOR

Study visits monthly (Week 0, 4, and 8), with phone visits every other week (Week 2 and 6). Double-blind, placebo-controlled treatment with escitalopram 10mg/day, raised to 20mg/day, if non-responders at week 4. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits.

Drug: Escitalopram

Research Frequency Management: Escitalopram

ACTIVE COMPARATOR

Weekly study visits, treatment with double-blind, placebo controlled escitalopram 10 mg/day, raised to 20mg/day at week 4 if non-responders. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits.

Drug: Escitalopram

Interventions

Escitalopram DRUG

Escitalopram is a Selective Serotonin Reuptake Inhibitor (SSRI) medication that appears to help with symptoms of depression by increasing the availability of specific chemicals in the brain.

Also known as: Lexapro

Clinical Frequency Management: Escitalopram; Research Frequency Management: Escitalopram

Placebo DRUG

A placebo (or dummy pill) is an inert (inactive) substance, typically a tablet, capsule or other dose form that does not contain an active drug ingredient.

Clinical Frequency Management: Placebo; Research Frequency Management: Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women aged 18-75 years 1. Clinical interview
• Diagnosis with Diagnostic and Statistical Manual (DSM) V Major Depressive Disorder (MDD) 2. Clinical interview, Structured Clinical Interview for DSM-V
• item Hamilton Rating Scale for Depression (HRSD) score ≥ 16 and ≤ 28; 17-item Hamilton Rating Scale for Depression (HRSD) score \< 25 3. HRSD by trained rater
• Capable of providing informed consent and complying with study procedures 4. Clinical interview
• Using appropriate contraceptive method if woman of child-bearing age and not currently pregnant 5. Clinical interview

You may not qualify if:

• Current comorbid Axis I DSM V disorder other than Mild Substance Use Disorder, Adjustment Disorder, Anxiety Disorder or Personality Disorder 1. Clinical interview, SCID
• Diagnosis of Moderate to Severe Substance Use Disorder within the past 12 months 2. Clinical interview, SCID, Urine tox
• present or past history of psychosis, psychotic disorder, mania, or bipolar disorder 3. Clinical interview, SCID
• baseline HRSD 24-item score \> 28 or HRSD suicide item \> 2 or baseline HRSD 17-item score ≥ 25 4. HRSD by trained rater
• History of allergic or adverse reaction to escitalopram, or non-response to adequate trial of escitalopram (at least 4 weeks at dose of 20mg) during the current episode 5. Clinical interview
• Current treatment with psychotherapy, antidepressants, antipsychotics, or mood stabilizers 6. Clinical interview
• CGI-Severity score of 6 or greater at baseline 7. CGI based on Clinical interview
• Acute, severe, or unstable medical illness 8. Clinical interview, Physical Exam, Screening Labs

Sponsors & Collaborators

• New York State Psychiatric Institute: lead
• University of Haifa: collaborator

Study Sites (1)

New York State Psychiatric Institute

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Escitalopram

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

Due to challenges associated with the pandemic, the study was completed with a smaller sample size than originally intended.

Results Point of Contact

• Title: Dr. Bret Rutherford
• Organization: New York State Psychiatric Institute

bret.rutherford@nyspi.columbia.edu

646-774-8660

Study Officials

• Bret Rutherford, MD

  New York State Psychiatric Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor in Clinical Psychiatry

Study Record Dates

• First Submitted: January 15, 2019
• First Posted: January 23, 2019
• Study Start: January 30, 2019
• Primary Completion: May 27, 2020
• Study Completion: August 1, 2021
• Last Updated: April 21, 2022
• Results First Posted: April 21, 2022

Record last verified: 2022-03

Locations

US (1)