Promoting Enhanced Pharmacotherapy Choice Through Immunomarkers Evaluation in Depression

NCT03993457 | Terminated Phase 4 Results FDA Drug

• 1 other identifier: STU-2019-0623
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

PRECISE-D is a single site, randomized, open label 8-week clinical trial that will enroll 70 participants to evaluate if the level of inflammation in our body can predict how we will respond to antidepressants. C-reactive protein (CRP) is a substance in the body that is associated with inflammation. Previous research has suggested that people with high CRP (i.e., high inflammation levels) tend to have greater improvement of depressive symptoms with an antidepressant called bupropion, while individuals with low CRP (i.e., low inflammation levels) appear to have more benefit from selective serotonin reuptake inhibitors antidepressants (SSRI), such as escitalopram. However, it is not completely clear if CRP can predict your response to these two antidepressants. Participants will undergo a screening visit that includes a physical exam, overall health evaluation, assessment of mental health history, and a toxicology and pregnancy test. Once screening is complete, participants will be randomized to one of two groups that will determine whether their CRP levels will be used to select which antidepressant they will receive. Participants will then complete 4 follow up visits at weeks 2, 4, 6, and 8. A follow-up phone call from the study team will occur at week 12.

Conditions

Depression

Keywords

depression; mental health; mood disorders; major depressive episode; major depressive disorder; antidepressants; escitalopram; bupropion; depression treatment

Outcome Measures

Primary Outcomes (3)

• Efficacy of CRP-consistent Antidepressant Selection Versus CRP-inconsistent Antidepressant Selection on Remission Rates in Patients With MDD.

  The primary study endpoint will be remission rates based on the 16-items Quick Inventory of Depressive Symptomatology, Self-Report (QIDS-SR), which will be extracted from the 30-item Inventory of Depressive Symptomatology (IDS-SR). The QIDS-SR score ranges from 0-27. A score of 5 or less represents remission.

  1 year

• Efficacy of CRP-consistent Antidepressant Selection Versus CRP-inconsistent Antidepressant Selection on Improving Social and Occupational Functioning.

  Improvement in social and occupational functioning will be measured with the 5-item self-administered Work and Social Adjustment Scale (WSAS). The WSAS total score ranges from 0-40. Lower scores are better.

  12 weeks

• Adverse Antidepressant Treatment Effects on CRP-consistent Antidepressant Selection Versus CRP-inconsistent Antidepressant Selection

  Side effects will be assessed using the 3-item self-administered Frequency, Intensity, and Burden of Side Effects (FIBSER). Each item is scored on a scale from 0-6. Items 1 and 2 (Frequency \& Intensity respectively) are to provide information to the clinician, but they are not used in the scoring.The score that is used comes only from Item 3 - Burden. Lower scores represents lower burden.

  1 year

Secondary Outcomes (1)

• Optional Sub-study. Validity and Reliability of Capillary Blood CRP Measurement

  Baseline

Study Arms (4)

CRP<1, CRP consistent antidepressant selection

OTHER

Participants with CRP\<1 will be prescribed escitalopram

Drug: Escitalopram

CRP> or equal to 1, CRP consistent antidepressant selection

OTHER

Participants with CRP\> or equal to 1 will be prescribed bupropion XL

Drug: Bupropion

CRP<1, CRP inconsistent antidepressant selection

OTHER

Participants with CRP\< 1 will be prescribed bupropion XL

Drug: Bupropion

CRP> or equal to 1, CRP inconsistent antidepressant selection

OTHER

Participants with CRP\> or equal to 1 will be prescribed escitalopram

Drug: Escitalopram

Interventions

Escitalopram DRUG

Escitalopram will be started at 5 mg/day during the first week of treatment. The dose will then be increased to 10mg/day, and can be increased to 20 mg/day. Dose can be decreased to 5 mg by clinician discretion such as to increase tolerability or better manage side-effects. 5 mg will be the lowest dose allowed in the study.

Also known as: Lexapro

CRP<1, CRP consistent antidepressant selection; CRP> or equal to 1, CRP inconsistent antidepressant selection

Bupropion DRUG

Bupropion-XL will be started at 150 mg/day and increased to 300 mg/day after one week. This dose can be increased to 450 mg/day (divided in 2 doses) at Week 2 or later. Clinicians may opt to titrate bupropion-XL in a slower fashion in cases that might increase tolerability or better manage side-effects. 150 mg will be the lowest dose allowed in the study.

Also known as: Wellbutrin XL

CRP<1, CRP inconsistent antidepressant selection; CRP> or equal to 1, CRP consistent antidepressant selection

Eligibility Criteria

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

You may qualify if:

• Women and men ages 18-65
• Current diagnosis of Major Depressive Disorder
• Able to read, speak, and understand English

You may not qualify if:

• Antidepressant use within the last 8 weeks
• Active infection or uncontrolled autoimmune disease
• Currently on oral corticosteroids or active immune suppressive therapy (methotrexate, cyclosporine, anti-cytokines medications, etc).
• Current diagnosis of uncontrolled HIV, hepatitis C or significant immunodeficiency
• Alcohol or substance use disorder
• Positive urine drug test for illicit substances or substances used out of the context of prescription
• Cognitively unable to give informed consent
• Pregnant or breastfeeding women, women of childbearing potential who are not using an accepted means of birth control, or women with a positive urine pregnancy test
• History of seizure disorder
• Previous significant adverse reaction to escitalopram or bupropion
• History of non-response to adequate doses of escitalopram or bupropion XL
• Current use of concomitant psychotropic agents (anticonvulsants, benzodiazepines, hypnotics, opiates, triiodothyronine (T3), modafinil, psychostimulants, buspirone, melatonin, folate, l-methylfolate, s-adenosyl methionine, lithium) not on the same dose for at least four weeks prior to study entry or who do not agree to continue at the same dose during the acute phase of the study.
• Lifetime history of bipolar disorder, schizophrenia, schizoaffective disorder or other psychotic disorder
• Current anorexia nervosa or bulimia nervosa
• Suicidal ideation of the degree that, in the opinion of the evaluating clinician, participation in the study would place them at significantly increased risk of suicide

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead

Study Sites (1)

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Depression; Psychological Well-Being; Mood Disorders; Depressive Disorder, Major

Interventions

Escitalopram; Bupropion

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Personal Satisfaction; Mental Disorders; Depressive Disorder

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Maria Monastirsky
• Organization: UTexasSouthwestern

maria.monastirsky@utsouthwestern.edu

214-648-0174

Study Officials

• Madhukar H Trivedi, MD

  UTSW

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Participant, care provider, investigator, and outcomes assessor will only be blinded to the participant's CRP levels and group assignment. However, the study is open label, meaning the participant, care provider, investigator, and outcomes assessor will know what medication the participant is taking.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Participants will be assigned to one of two groups based on their CRP levels: * CRP less than 1 * CRP greater than or equal to 1 Participants within both groups will then be randomized to one of 2 groups, which is stratified by a CRP group: * CRP consistent antidepressant selection (medication will be prescribed based on CRP level) * CRP inconsistent antidepressant selection (medication will be prescribed in contradiction to CRP level)

Study Record Dates

• First Submitted: June 13, 2019
• First Posted: June 20, 2019
• Study Start: July 23, 2019
• Primary Completion: March 25, 2022
• Study Completion: March 25, 2022
• Last Updated: April 18, 2023
• Results First Posted: April 18, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)