The ISLAND Study: InSuLa Assessed Needs for Depression

Study Overview
=================
Brief Summary
-----------------
While there are many effective options for treating a major depressive episode, there are no clinical markers that predict the likelihood of remission with an initial trial of either an antidepressant medication or psychotherapy. The goal of this study is to test how brain function changes in depress patients treated with cognitive behavioral therapy (CBT) compared to patients treated with a selective serotonin reuptake inhibitor (SSRI, either escitalopram or sertraline), which are FDA approved antidepressants. The study aims to determine if bran scan findings might help physicians to select the most effective antidepressant treatment for an individual patient. Up to 100 male and female outpatients who are between 21-55 years old will be enrolled. Participation in the study will last from 14-26 weeks. Subjects will be randomized to receive either escitalopram (s-CIT) or CBT for 12 weeks. Resting-state positron emission tomography (PET) and BOLD functional magnetic resonance imaging (fMRI) scans will be done before the treatment begins, and again at the end of treatment (week 12). Non-responders to s-cIT or CBT will be crossed over to receive an additional 12 weeks of treatment with the alternative intervention.

Official Title
-----------------
Testing an Imaging Biomarker for Treatment Stratification in Major Depression

Conditions
-----------------
Depression

Intervention / Treatment
-----------------
* Drug: Selective serotonin re-uptake inhibitor
* Behavioral: Cognitive Behavioral Therapy
* Other: Combination treatment (SSRI + CBT)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Men or women aged 18-60 years. Primary psychiatric diagnosis of Major Depressive Disorder, without psychotic features, confirmed via SCID-IV structured diagnostic interview. Screening Hamilton Depression Rating Scale (HAMD) ≥ 18; and Baseline HAMD ≥ 15. If the patient is a woman of child-bearing potential, she must agree to use an acceptable form of birth control for duration of study participation. Able to understand and provide informed consent for participation. Exclusion Criteria: Lifetime history of Bipolar Disorder, Dementia, Autism Spectrum Disorder, Schizophrenia, or any other Psychotic Disorder. Psychotic symptoms occurring at any time during the current major depressive episode. Current (past 12 months) diagnosis of Panic disorder, Obsessive Compulsive Disorder, Posttraumatic Stress Disorder, Anorexia Nervosa, or Bulimia Nervosa. Alcohol or Drug Dependence within 12 months or Abuse within 3 months (excluding nicotine and caffeine) of baseline visit, as assessed by history and urine drug screen. Clinical evidence of a severe Personality Disorder, as assessed by the study psychiatrist, which would impede participation or completion of the trial. Known neurological disorders or documented serious head injury. Serious and unstable medical illnesses including cardiovascular disease and cancer. Active medical conditions with known mood changes (endocrine, autoimmune disorders). Current diabetes mellitus. For women, pregnancy, lactation, or unwillingness to comply with birth control requirements. Use of any of the following treatments or any other alternative therapy within 2 weeks of the pre-treatment PET scan that may have beneficial effects on mood, including St John's Wort, S-adenosyl methionine (SAMe), n-3 fatty acids, or light therapy. Use of antidepressant medication within 1 month of the pre-treatment PET scan (within 5 weeks for fluoxetine and protryptyline). Failure to achieve a much improved status (i.e. equivalent to >50% symptom reduction) with 1) any lifetime treatment course of CBT (defined as a minimum of 4 sessions of a specified manual-driven therapy by a CBT-trained therapist) or 2) both escitalopram and sertraline (defined as a minimum of 6 weeks of at the minimum effective dose). Clinically significant active suicidal ideation or self-injurious behavior necessitating immediate treatment, as determined by the investigator. Received electroconvulsive therapy in the past 6 months or during the current depressive episode. Currently responding to medication treatment, without clinical reasons to change. Current treatment with weekly individual or group psychotherapy of any type targeted at depressive symptoms. QTc >500 milliseconds on EKG at screening. Contraindications for MRI, including, but not limited to pacemaker, aneurysm clips, neurostimulators, cochlear implants, metal in eyes, steel worker, intra-uterine devices for birth control. Use of concomitant medications with the exception of: Maintenance or prophylactic therapy for stable medical conditions. Hypnotic medication prescribed or approved by the study physician, (up to a three doses per week) for insomnia, as long if not the night before a PET/MRI or clinic ratings visit. Antipsychotic medications, whether prescribed for sleep or other indications, are prohibited.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: SSRI<br>Escitalopram, pill form, 20mg-40mg, daily, for 12 weeks or Sertraline, pill form, 50 - 150 mg, daily for 12 weeks | Drug: Selective serotonin re-uptake inhibitor<br>* Escitalopram, 20mg-40mg daily or Sertraline 50-150 mg daily for 12 weeks<br>* Other names: Depression treatment;Other: Combination treatment (SSRI + CBT)<br>* study participants who do not remit in the first 12 weeks will be offered combination treatment of both treatments for 12 more weeks.<br>* Other names: depression trial;|
| Active Comparator: Cognitive Behavioral Therapy<br>Cognitive Behavioral Therapy (CBT) CBT will include 16 1-hour sessions provided over 12 weeks. | Behavioral: Cognitive Behavioral Therapy<br>* Cognitive Behavioral Therapy, standardized, 16 sessions over 12 weeks.<br>* Other names: Talk therapy;Other: Combination treatment (SSRI + CBT)<br>* study participants who do not remit in the first 12 weeks will be offered combination treatment of both treatments for 12 more weeks.<br>* Other names: depression trial;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Remission From Major Depressive Episode Events | Remission from major depressive episode as assessed by 17-item Hamilton Depression Rating Scale. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Response to Treatment Events | Response Defined as 50% Change in Hamilton Depression Rating Scale-17 Score at 12 Weeks | 12 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
MDD, Major Depressive Disorder, Treatment, Antidepressants, Lexapro, Talk therapy