The ISLAND Study: InSuLa Assessed Needs for Depression

• Sponsor: Emory University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02137369
• Collaborator: National Institute of Mental Health (NIMH) (NIH)
• Enrollment: 77
• Location: 1
• Arms: 2
• Duration (Months): 61.7
• Patients Per Site Per Month: 1.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Depression	Drug: Selective serotonin re-uptake inhibitor; Behavioral: Cognitive Behavioral Therapy; Other: Combination treatment (SSRI + CBT)	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 77 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Testing an Imaging Biomarker for Treatment Stratification in Major Depression
• Study Start Date: Sep 1, 2014
• Actual Primary Completion Date: Oct 24, 2019
• Actual Study Completion Date: Oct 24, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: SSRI 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; Escitalopram, 20mg-40mg daily or Sertraline 50-150 mg daily for 12 weeks; Other Names: Escitalopram or Sertraline SSRI Antidepressant medication Depression treatment ; Other: Combination treatment (SSRI + CBT); study participants who do not remit in the first 12 weeks will be offered combination treatment of both treatments for 12 more weeks.; Other Names: Crossover treatment escitalopram depression treatment antidepressant talk therapy depression trial
Active Comparator: Cognitive Behavioral Therapy Cognitive Behavioral Therapy (CBT) CBT will include 16 1-hour sessions provided over 12 weeks.	Behavioral: Cognitive Behavioral Therapy; Cognitive Behavioral Therapy, standardized, 16 sessions over 12 weeks.; Other Names: CBT Depression Treatment Talk therapy ; Other: Combination treatment (SSRI + CBT); study participants who do not remit in the first 12 weeks will be offered combination treatment of both treatments for 12 more weeks.; Other Names: Crossover treatment escitalopram depression treatment antidepressant talk therapy depression trial

Outcome Measures

Primary Outcome Measures

1. Number of Remission From Major Depressive Episode Events [12 weeks]

   Remission from major depressive episode as assessed by 17-item Hamilton Depression Rating Scale.

Secondary Outcome Measures

1. Number of Response to Treatment Events [12 weeks]

   Response Defined as 50% Change in Hamilton Depression Rating Scale-17 Score at 12 Weeks

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Men or women aged 18-60 years.

2. Primary psychiatric diagnosis of Major Depressive Disorder, without psychotic features, confirmed via SCID-IV structured diagnostic interview.

3. Screening Hamilton Depression Rating Scale (HAMD) ≥ 18; and Baseline HAMD ≥ 15.

4. 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.

5. Able to understand and provide informed consent for participation.

Exclusion Criteria:

1. Lifetime history of Bipolar Disorder, Dementia, Autism Spectrum Disorder, Schizophrenia, or any other Psychotic Disorder.

2. Psychotic symptoms occurring at any time during the current major depressive episode.

3. Current (past 12 months) diagnosis of Panic disorder, Obsessive Compulsive Disorder, Posttraumatic Stress Disorder, Anorexia Nervosa, or Bulimia Nervosa.

4. 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.

5. Clinical evidence of a severe Personality Disorder, as assessed by the study psychiatrist, which would impede participation or completion of the trial.

6. Known neurological disorders or documented serious head injury.

7. Serious and unstable medical illnesses including cardiovascular disease and cancer.

8. Active medical conditions with known mood changes (endocrine, autoimmune disorders).

9. Current diabetes mellitus.

10. For women, pregnancy, lactation, or unwillingness to comply with birth control requirements.

11. 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.

12. Use of antidepressant medication within 1 month of the pre-treatment PET scan (within 5 weeks for fluoxetine and protryptyline).

13. 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).

14. Clinically significant active suicidal ideation or self-injurious behavior necessitating immediate treatment, as determined by the investigator.

15. Received electroconvulsive therapy in the past 6 months or during the current depressive episode.

16. Currently responding to medication treatment, without clinical reasons to change.

17. Current treatment with weekly individual or group psychotherapy of any type targeted at depressive symptoms.

18. QTc >500 milliseconds on EKG at screening.

19. 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.

20. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	12 Executive Park Drive, 3rd floor	Atlanta	Georgia	United States	30329

Sponsors and Collaborators

• Emory University
• National Institute of Mental Health (NIMH)

Investigators

• Principal Investigator: Boadie W Dunlop, MD/MS, Emory University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 24, 2014

More Information

Additional Information:

• Study information

Publications

None provided.

• Responsible Party: Boadie W. Dunlop, Professor, Emory University
• ClinicalTrials.gov Identifier: NCT02137369
• Other Study ID Numbers: IRB00073702; R01MH073719; 00073702
• First Posted: May 13, 2014
• Last Update Posted: Nov 5, 2020
• Last Verified: Oct 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Boadie W. Dunlop, Professor, Emory University: MDD; Major Depressive Disorder; Treatment; Antidepressants; Lexapro; Talk therapy
• Additional relevant MeSH terms: Depression; Depressive Disorder; Dexetimide; Citalopram; Sertraline; Antidepressive Agents; Serotonin Uptake Inhibitors; Serotonin

Study Results

Participant Flow

Pre-assignment Detail	77 were consented, 60 started treatments

Arm/Group Title	SSRI	Cognitive Behavioral Therapy
Arm/Group Description	Escitalopram, pill form, 20mg-40mg, daily, for 12 weeks OR Sertraline, pill form, 50-150 mg, daily for 12 weeks.	Cognitive Behavioral Therapy (CBT) Cognitive Behavioral Therapy: Cognitive Behavioral Therapy, standardized, 16 1-hour sessions over 12 weeks.
Period Title: Overall Study
STARTED	49	11
COMPLETED	41	9
NOT COMPLETED	8	2

Baseline Characteristics

Arm/Group Title	SSRI	Cognitive Behavioral Therapy	Total
Arm/Group Description	Escitalopram, pill form, 20mg-40mg, daily, for 12 weeks OR Sertraline, pill form, 50-150 mg, daily, for 12 weeks	Cognitive Behavioral Therapy (CBT) CBT will include 16 1-hour standardized sessions provided over 12 weeks.	Total of all reporting groups
Overall Participants	49	11	60
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	49 100%	11 100%	60 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	35 71.4%	8 72.7%	43 71.7%
Male	14 28.6%	3 27.3%	17 28.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	2 4.1%	0 0%	2 3.3%
Asian	1 2%	0 0%	1 1.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	11 22.4%	4 36.4%	15 25%
White	28 57.1%	6 54.5%	34 56.7%
More than one race	4 8.2%	1 9.1%	5 8.3%
Unknown or Not Reported	3 6.1%	0 0%	3 5%
Region of Enrollment (participants) [Number]
United States	49 100%	11 100%	60 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	SSRI	Cognitive Behavioral Therapy
Arm/Group Description	Escitalopram, pill form, 20mg-40mg, daily, for 12 weeks, OR Sertraline, [pill form, 50-150 mg, daily for 12 weeks	Cognitive Behavioral Therapy (CBT) CBT will include 16 1-hour sessions provided over 12 weeks. Cognitive Behavioral Therapy: Cognitive Behavioral Therapy, standardized, 16 sessions over 12 weeks.
Measure Participants	49	11
Number [number of events]	15	4

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	SSRI	Cognitive Behavioral Therapy
Arm/Group Description	Escitalopram, pill form, 20mg-40mg, daily, for 12 weeks, OR Sertraline, pill form, 50-150 mg, daily, for 12 weeks	Cognitive Behavioral Therapy (CBT) CBT will include 16 1-hour sessions provided over 12 weeks. Cognitive Behavioral Therapy: Cognitive Behavioral Therapy, standardized, 16 sessions over 12 weeks.
Measure Participants	49	11
Number [number of events]	21	5

Adverse Events

Time Frame	12 weeks
Arm/Group Title	SSRI		Cognitive Behavioral Therapy
Arm/Group Description	Escitalopram, pill form, 20mg-40mg, daily, for 12 weeks OR Sertraline, pill form, 50-150 mg, daily, for 12 weeks		Cognitive Behavioral Therapy (CBT) Cognitive Behavioral Therapy: Cognitive Behavioral Therapy, standardized, 16 1-hour sessions over 12 weeks.
All Cause Mortality
	SSRI		Cognitive Behavioral Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/49 (0%)		0/11 (0%)
Serious Adverse Events
	SSRI		Cognitive Behavioral Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/49 (2%)		0/11 (0%)
Psychiatric disorders
Hospitalization for suicidal ideation	1/49 (2%)	1	0/11 (0%)	0
Other (Not Including Serious) Adverse Events
	SSRI		Cognitive Behavioral Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	44/49 (89.8%)		5/11 (45.5%)
Cardiac disorders
Palpitations	2/49 (4.1%)	2	0/11 (0%)	0
Ear and labyrinth disorders
Tinnitus	1/49 (2%)	1	0/11 (0%)	0
Eye disorders
Blurred vision	3/49 (6.1%)	3	0/11 (0%)	0
Iritis	1/49 (2%)	1	0/11 (0%)	0
Gastrointestinal disorders
Nausea	12/49 (24.5%)	13	0/11 (0%)	0
Diarea	8/49 (16.3%)	9	0/11 (0%)	0
Constipation	2/49 (4.1%)	2	0/11 (0%)	0
Gastroenteritis	2/49 (4.1%)	2	0/11 (0%)	0
Vomiting	2/49 (4.1%)	2	0/11 (0%)	0
General disorders
Headache	19/49 (38.8%)	21	1/11 (9.1%)	1
Reduced Concentration	7/49 (14.3%)	7	0/11 (0%)	0
Fatigue	7/49 (14.3%)	7	0/11 (0%)	0
Sweating	4/49 (8.2%)	4	0/11 (0%)	0
Yawning	4/49 (8.2%)	4	0/11 (0%)	0
Reduced Appetite	3/49 (6.1%)	3	0/11 (0%)	0
Feeling hot	2/49 (4.1%)	2	0/11 (0%)	0
Abdominal pain	2/49 (4.1%)	2	0/11 (0%)	0
Dry mouth	2/49 (4.1%)	2	0/11 (0%)	0
Increased Appetite	1/49 (2%)	1	0/11 (0%)	0
Chest pain	1/49 (2%)	1	0/11 (0%)	0
Epistaxis	1/49 (2%)	1	0/11 (0%)	0
Weight gain	1/49 (2%)	1	0/11 (0%)	0
Difficulty swallowing	1/49 (2%)	1	0/11 (0%)	0
Infections and infestations
Fungal infection	1/49 (2%)	1	0/11 (0%)	0
Mouth Sores	1/49 (2%)	1	0/11 (0%)	0
Injury, poisoning and procedural complications
Laceration	1/49 (2%)	1	0/11 (0%)	0
Musculoskeletal and connective tissue disorders
Musculoskeletal pain	8/49 (16.3%)	9	1/11 (9.1%)	1
Plantar fascitis	1/49 (2%)	1	0/11 (0%)	0
Jaw tightness	1/49 (2%)	1	0/11 (0%)	0
Nervous system disorders
Insomnia	9/49 (18.4%)	10	0/11 (0%)	0
Dizziness	6/49 (12.2%)	6	0/11 (0%)	0
Restlessness	4/49 (8.2%)	4	0/11 (0%)	0
Paresthesia	4/49 (8.2%)	4	0/11 (0%)	0
Abnormal Dreams	3/49 (6.1%)	3	0/11 (0%)	0
Psychiatric disorders
Anxiety	9/49 (18.4%)	9	0/11 (0%)	0
Cognitive slowing	1/49 (2%)	1	0/11 (0%)	0
Myoclonic jerks	1/49 (2%)	1	0/11 (0%)	0
Emotional blunting	1/49 (2%)	1	0/11 (0%)	0
Panic Attack	1/49 (2%)	1	0/11 (0%)	0
Worsening depression	1/49 (2%)	1	0/11 (0%)	0
Renal and urinary disorders
Renal calculus	1/49 (2%)	1	0/11 (0%)	0
Increased Urination	1/49 (2%)	1	0/11 (0%)	0
Reproductive system and breast disorders
Libido reduced	5/49 (10.2%)	5	0/11 (0%)	0
Erectile dysfunction	3/49 (6.1%)	3	0/11 (0%)	0
Ovarian Cyst	1/49 (2%)	1	0/11 (0%)	0
Orgasm abnormal	1/49 (2%)	1	0/11 (0%)	0
Cervical dysplasia	1/49 (2%)	1	0/11 (0%)	0
Bacterial vaginosis	1/49 (2%)	1	0/11 (0%)	0
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract infection	8/49 (16.3%)	8	2/11 (18.2%)	2
Cough	3/49 (6.1%)	3	1/11 (9.1%)	1
Bronchitis	1/49 (2%)	1	0/11 (0%)	0
Skin and subcutaneous tissue disorders
Rash	2/49 (4.1%)	2	0/11 (0%)	0
Cellulitis	1/49 (2%)	1	0/11 (0%)	0
Surgical and medical procedures
Sedation	8/49 (16.3%)	8	1/11 (9.1%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.