Advancing Personalized Antidepressant Treatment Using PET/MRI

NCT02623205 | Completed Phase 4 Results DMC

• 1 other identifier: 2014-2911-F
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 1

Brief Summary

Despite current medications, morbidity and mortality of Major Depressive Disorder (MDD) remain high. According to the World Health Organization, MDD affects 121 million people worldwide, and is projected to be the second leading cause of global disability by 2020. Monotherapy with selective serotonin reuptake inhibitors (SSRIs) is the most widely used treatment for MDD. However, on average, SSRIs require six weeks for onset of action, and two-thirds of those on SSRIs fail to achieve remission. Compounding this problem, patients with residual symptoms are significantly more likely to discontinue treatment or relapse, be hospitalized for medical and psychiatric conditions, or die of suicide and other causes. Although eliminating ineffective treatment trials would significantly reduce patient suffering and healthcare costs,clinicians currently do not have the tools to objectively select treatment based on an individual's likelihood of remission. Therefore, there is an urgent need to identify markers predictive of an individual's SSRI treatment outcome. Developing this personalized treatment requires increased understanding of the relationship between pretreatment neurobiology, SSRI-induced biological changes, and the corresponding symptom improvements.

Conditions

Depression

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Hamilton Depression Rating Scale at 8 Weeks

  Comparison of Hamilton Depression Rating Scale-17 score at pretreatment and post-treatment. Minimum score 0, maximum possible score 52, with remission defined as \<=7. The higher the score on the scale, the more severe the degree of depression.

  8 weeks

Secondary Outcomes (4)

• Change From Baseline in Metabolic Rate of Glucose (MRGlu), Quantified Using Arterial Blood Analysis, at 8 Weeks

  8 weeks

• Quantification of Brain MRGlu Without an Arterial Catheter by Training Simultaneous Estimation (SimE)

  Baseline

• Bias of VersaPET Scanner From Measurements Taken at the Wrist and Ankle

  Baseline

• Correlation Coefficient of VersaPET Scanner From Measurements Taken at the Wrist or Ankle

  Baseline

Study Arms (2)

Escitalopram

ACTIVE COMPARATOR

Active Comparator: Escitalopram (Lexapro) 10mg Week 1, 20mg Weeks 2 and 3, and 30mg for Weeks 4 to 8 (or until 12 for patients close to remission)

Drug: Escitalopram

Placebo

PLACEBO COMPARATOR

Lactose pill manufactured to mimic Escitalopram pill

Drug: Placebo

Interventions

Escitalopram DRUG

Participants randomized to the escitalopram group will be given the medication for 8 weeks, after which they will be given the option to continue for 4 more weeks if they are close to remission. This additional 4-week treatment option is something offered to participants outside the clinical trial, and therefore was not treated as part of the main study.

Also known as: Lexapro

Escitalopram

Placebo DRUG

To reduce the burden of the patients on placebo, the placebo trial will have a target of 8 weeks. To provide an opportunity for placebo non-responders to receive active drug and to aid in recruitment, we will provide 8-12 weeks of SSRI treatment to placebo non-responders. This treatment option is something offered to participants outside the clinical trial, and therefore was not treated as part of the main study.

Also known as: Lactose pill

Placebo

Eligibility Criteria

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

You may qualify if:

• Age range: over 18 years old
• Capacity to consent
• Diagnosis of MDD and suffering from a major depressive episode
• Score of at least 22 on the MADRS

You may not qualify if:

• Significant active physical illness, particularly those that may affect the brain
• Need for use of medication during the study that will interact with the study medication. Need to start medication that will affect study results (anti epileptics, antidepressants, beta blockers, medications with serotonergic or GABAergic modes of action)
• Patients considered at significant risk for suicide
• Patient is unlikely to be able to tolerate medication washout or the \~3 week interval (5 for fluoxetine) following washout (drug free period). Medication washouts will be supervised by a study physician.
• For females: Pregnancy, currently lactating; planning to conceive during the course of study participation, or abortion in the past two months.
• Coumadin treatment within 10 days of PET scanning
• Any MRI contraindications, including metal implants, pacemaker, metal prostheses, orthodontic appliances, or presence of shrapnel that are contraindicated for MRI.
• Bipolar Disorder
• Current psychosis
• High potential for excessive drug/alcohol use during the treatment period (excluding nicotine or cannabis)
• Currently taking effective antidepressant
• Currently taking an effective antidepressant
• Prior intolerance escitalopram (ESC) for ≥ 4 weeks taking ≥ ⅔ Physician's Desk Reference (PDR) maximal dose
• Significant neurological deficits
• Electroconvulsive Therapy (ECT) within the past 6 months

Sponsors & Collaborators

• Stony Brook University: lead

Study Sites (1)

Stony Brook University Hospital

Stony Brook, New York, 11794, United States

Location

Related Publications (2)

• Dai F, Wengler K, He X, Wang J, Yang J, Parsey RV, DeLorenzo C. Lack of association between pretreatment glutamate/GABA and major depressive disorder treatment response. Transl Psychiatry. 2025 Mar 2;15(1):71. doi: 10.1038/s41398-025-03292-9.

  PMID: 40025010 DERIVED

• Narayan GA, Hill KR, Wengler K, He X, Wang J, Yang J, Parsey RV, DeLorenzo C. Does the change in glutamate to GABA ratio correlate with change in depression severity? A randomized, double-blind clinical trial. Mol Psychiatry. 2022 Sep;27(9):3833-3841. doi: 10.1038/s41380-022-01730-4. Epub 2022 Aug 18.

  PMID: 35982258 DERIVED

MeSH Terms

Conditions

Depression

Interventions

Escitalopram; Lactose

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; Disaccharides; Oligosaccharides; Polysaccharides; Carbohydrates; Sugars

Results Point of Contact

• Title: Kathryn Hill
• Organization: Department of Psychiatry, Renaissance School of Medicine at Stony Brook University

kathryn.hill@stonybrookmedicine.edu

904-252-3449

Study Officials

• Christine DeLorenzo, PhD

  Stony Brook University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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, Associate Professor of Biomedical Engineering

Study Record Dates

• First Submitted: December 1, 2015
• First Posted: December 7, 2015
• Study Start: May 1, 2015
• Primary Completion: March 1, 2020
• Study Completion: March 1, 2020
• Last Updated: December 15, 2022
• Results First Posted: June 2, 2022

Record last verified: 2022-12

Locations

US (1)