Differentiating Unipolar and Bipolar Depression in Young Adults Using fMRI

• Sponsor: The Cleveland Clinic (Other)
• Overall Status: Completed
• CT.gov ID: NCT01811147
• Collaborator: (none)
• Enrollment: 192
• Location: 1
• Arms: 4
• Duration (Months): 79
• Patients Per Site Per Month: 2.4

Study Details

Study Description

Brief Summary

The purpose of the study is to find out what parts of the brain have increased or decreased activity and connectivity in individuals who have bipolar disorder, major depression, or no history of mood disorder. Another purpose of this study is to use MRI images to determine which young adults with major depression may be at greater risk for developing mild or more severe symptoms of mania which suggests a diagnosis of bipolar disorder.

Condition or Disease	Intervention/Treatment	Phase
Bipolar Disorder; Major Depression	Drug: Selective Serotonin Reuptake Inhibitor (SSRI)	Phase 4

Detailed Description

The study involves two phases, phase one includes the screening visit and MRI. The second phase, for depression participants, involves in person follow ups for up to two years. The second phase, for healthy and bipolar participants, involves phone follow ups, every three months for up to two years. The purpose of this study is listed above. We plan to enroll 200 participants total.

Study Design

• Study Type: Interventional
• Actual Enrollment: 192 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Differentiating Unipolar and Bipolar Depression in Young Adults Using fMRI
• Study Start Date: Nov 1, 2011
• Actual Primary Completion Date: Jun 1, 2018
• Actual Study Completion Date: Jun 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: High Risk Depression Interventions will include the prescribing of Selective serotonin reuptake inhibitor or Serotonin-norepinephrine reuptake inhibitor antidepressants, bupropion or other antidepressant.	Drug: Selective Serotonin Reuptake Inhibitor (SSRI); Subjects with depression will be treated with a Selective Serotonin Reuptake Inhibitor (SSRI) or a Serotonin-norepinephrine reuptake inhibitor (SNRI) for 24 months.; Other Names: Serotonin-norepinephrine reuptake inhibitor
Experimental: Low Risk Depression Interventions will include the prescribing of Selective serotonin reuptake inhibitor or Serotonin-norepinephrine reuptake inhibitor antidepressants, bupropion or other antidepressant..	Drug: Selective Serotonin Reuptake Inhibitor (SSRI); Subjects with depression will be treated with a Selective Serotonin Reuptake Inhibitor (SSRI) or a Serotonin-norepinephrine reuptake inhibitor (SNRI) for 24 months.; Other Names: Serotonin-norepinephrine reuptake inhibitor
No Intervention: Healthy Control There is no intervention, but rather phone follow ups conducted as check ins to determine the continued eligibility of the healthy control participant.
No Intervention: Bipolar Bipolar participants are checked in with via phone conversations every three months, and have the opportunity to be scheduled for non-study visits to manage their symptoms.

Outcome Measures

Primary Outcome Measures

1. HAM-D 17 Item: Hamilton Depression Rating Scale [24 months]

   Hamilton depression rating scale (17-item HAM-D): Scores can range from 0 to 52: No depression (0-7); Mild depression (8-16); Moderate depression (17-23); and Severe depression (≥24).

Secondary Outcome Measures

1. YMRS: Young Mania Rating Scale [24 months]

   Young Mania Rating Scale: Scores can range from 0 to 60: In Remission/No Mania (0-8); Mild (9-12); Moderate (13-18); Severe (19-25); Very Severe (>25)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 15 Years to 30 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

INCLUSION CRITERIA FOR BIPOLAR DEPRESSED PATIENTS:

1. Ages 15 - 30 years (inclusive) and able to give voluntary informed consent (parents must also sign consent for subjects under 18)

2. Satisfy criteria for Diagnostic and Statistical Manual 4th edition (DSM-IV-TR) for Bipolar I or II disorder

3. Satisfy criteria for DSM-IV depressive episode-current

4. 17-item Hamilton Depression Rating Scale > 15 but < 25;

5. Young Mania Rating Scale score < 10

6. Satisfy criteria to undergo an MRI scan based on MRI screening questionnaire.

7. Able to be managed as outpatients during the study as ascertained by the following -

1. Clinical Global Severity Scale < 5 i.e. moderately ill; ii. No significant suicidal or homicidal ideation or grossly disabled.

INCLUSION CRITERIA FOR ALL UNIPOLAR DEPRESSED PATIENTS:

1. Ages 15 - 30 years and able to give voluntary informed consent (Parental consent must also be obtained for those under 18 years old).

2. Satisfy criteria for DSM-IV-TR Major Depressive Episode using a Structured Interview

3. Never met criteria for mania or hypomania

4. 17-item Hamilton Depression Rating Scale score (HDRS) > 15 and < 25.

5. Young Mania Rating Scale (YMRS) score < 10

6. Satisfy safety criteria to undergo an MRI scan

7. Able to be managed as outpatients during the study as ascertained by the following -

1. Clinical Global Severity Scale < 5 i.e. moderately ill; ii. No significant suicidal or homicidal ideation or grossly disabled

ADDITIONAL INCLUSION CRITERIA FOR HIGH RISK UD (HRUD) PATIENTS BESIDE THE INCLUSION

CRITERIA FOR UD:

At least one of the following:

1. Family history of bipolar disorder in at least one first degree relative

2. History of any sub-threshold hypomania symptoms

3. History of mood episode related psychotic symptoms

ADDITIONAL INCLUSION CRITERIA FOR LOW RISK UD (HRUD) PATIENTS BESIDE THE INCLUSION CRITERIA

FOR UD:

1. No family history of BD in a first or a second degree relative

2. No past history of any sub-threshold hypomania symptoms

3. No history of psychotic symptoms

EXCLUSION CRITERIA FOR DEPRESSION AND BIPOLAR SUBJECTS:

1. Meeting DSM-IV criteria for schizophrenia, schizophreniform disorder, schizoaffective disorder, mental retardation, pervasive developmental disorder.

2. History of receiving electroconvulsive therapy in the past 1 year

3. Use of neuroleptics, mood stabilizers or benzodiazepines in the past 2 weeks.

4. Use of antidepressants in the past 2 weeks.

5. If on fluoxetine in the past, then should not have been on this medication for 5 weeks.

6. Acutely suicidal or homicidal or requiring inpatient treatment.

7. Meeting DSM-IV criteria for other substance/alcohol dependence within the past 6 months or abuse in the past 3 months, excluding caffeine or nicotine. The criteria will be evaluated by interview and urinary toxicology screening. The use of caffeine or nicotine will be recorded.

8. Use of alcohol in the past 1 week before the MRI scan.

9. No serious acute or chronic medical or neurological illness, including previously known HIV positive status (due to possible CNS involvement) as assessed by history, physical examination and laboratory examination including EKG, CBC and blood chemistry.

10. Current pregnancy or breast feeding.

11. Metallic implants or other contraindication to MRI.

INCLUSION CRITERIA FOR HEALTHY CONTROLS: Healthy subjects matched for age, gender and ethnicity will be included

1. Ages 15 - 30 years (inclusive) and able to give voluntary informed consent (Parental consent must also be obtained for those under 18 years old)

2. No current or past history of psychiatric illness or substance abuse or dependence.

3. No current or past history of psychiatric illness or substance abuse or dependence in a first degree relative.

EXCLUSION CRITERIA FOR HEALTHY CONTROLS:

1. Pregnant or breast feeding.

2. Metallic implants or other contraindication to MRI.

3. Significant family history of psychiatric or neurological illness.

4. Currently taking any prescription or centrally acting medications.

5. Serious acute or chronic medical or neurological illness as assessed by history, physical examination and laboratory examination including CBC and blood chemistry.

6. Use of alcohol in the past 1 week and not being able to avoid alcohol use during the course of the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cleveland Clinic Foundation Center for Behavioral Health	Cleveland	Ohio	United States	44195

Sponsors and Collaborators

• The Cleveland Clinic

Investigators

• Principal Investigator: Amit Anand, MD, The Cleveland Clinic

Study Documents (Full-Text)

• Study Protocol: Image Acquisition - CCF - Jul 28, 2014
• Study Protocol and Statistical Analysis Plan: Full Protocol - Jul 28, 2014

More Information

Publications

None provided.

• Responsible Party: The Cleveland Clinic
• ClinicalTrials.gov Identifier: NCT01811147
• Other Study ID Numbers: IRB 12-1279
• First Posted: Mar 14, 2013
• Last Update Posted: Dec 2, 2019
• Last Verified: Nov 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Keywords provided by The Cleveland Clinic: Bipolar; Depression; Mania; Hypomania; fMRI; antidepressant
• Additional relevant MeSH terms: Depression; Depressive Disorder; Bipolar Disorder; Norepinephrine; Serotonin; Serotonin Uptake Inhibitors

Study Results

Participant Flow

Pre-assignment Detail	After enrollment 3 subject were excluded form the study since it was later discovered that they did not meet the criteria.

Arm/Group Title	High Risk Depression	Low Risk Depression	Healthy Control	Bipolar
Arm/Group Description	Interventions will include the prescribing of Selective serotonin reuptake inhibitor or Serotonin-norepinephrine reuptake inhibitor antidepressants, bupropion or other antidepressant. Selective Serotonin Reuptake Inhibitor (SSRI): Subjects with depression will be treated with a Selective Serotonin Reuptake Inhibitor (SSRI) or a Serotonin-norepinephrine reuptake inhibitor (SNRI) for 24 months.	Interventions will include the prescribing of Selective serotonin reuptake inhibitor or Serotonin-norepinephrine reuptake inhibitor antidepressants, bupropion or other antidepressant.. Selective Serotonin Reuptake Inhibitor (SSRI): Subjects with depression will be treated with a Selective Serotonin Reuptake Inhibitor (SSRI) or a Serotonin-norepinephrine reuptake inhibitor (SNRI) for 24 months.	There is no intervention, but rather phone follow ups conducted as check ins to determine the continued eligibility of the healthy control participant.	Bipolar participants are checked in with via phone conversations every three months, and have the opportunity to be scheduled for non-study visits to manage their symptoms.
Period Title: Overall Study
STARTED	51	56	49	33
COMPLETED	15	11	6	4
NOT COMPLETED	36	45	43	29

Baseline Characteristics

Arm/Group Title	High Risk Depression	Low Risk Depression	Healthy Control	Bipolar	Total
Arm/Group Description	Interventions will include the prescribing of Selective serotonin reuptake inhibitor or Serotonin-norepinephrine reuptake inhibitor antidepressants, bupropion or other antidepressant. Selective Serotonin Reuptake Inhibitor (SSRI): Subjects with depression will be treated with a Selective Serotonin Reuptake Inhibitor (SSRI) or a Serotonin-norepinephrine reuptake inhibitor (SNRI) for 24 months.	Interventions will include the prescribing of Selective serotonin reuptake inhibitor or Serotonin-norepinephrine reuptake inhibitor antidepressants, bupropion or other antidepressant.. Selective Serotonin Reuptake Inhibitor (SSRI): Subjects with depression will be treated with a Selective Serotonin Reuptake Inhibitor (SSRI) or a Serotonin-norepinephrine reuptake inhibitor (SNRI) for 24 months.	There is no intervention, but rather phone follow ups conducted as check ins to determine the continued eligibility of the healthy control participant.	Bipolar participants are checked in with via phone conversations every three months, and have the opportunity to be scheduled for non-study visits to manage their symptoms.	Total of all reporting groups
Overall Participants	51	56	49	33	189
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	22.67 (3.433)	25.27 (3.661)	24.24 (3.339)	23.52 (3.784)	23.99 (3.655)
Sex: Female, Male (Count of Participants)
Female	40 78.4%	38 67.9%	28 57.1%	22 66.7%	128 67.7%
Male	11 21.6%	18 32.1%	21 42.9%	11 33.3%	61 32.3%
Race/Ethnicity, Customized (Count of Participants)
Caucasian	37 72.5%	50 89.3%	37 75.5%	26 78.8%	150 79.4%
African American	13 25.5%	6 10.7%	4 8.2%	7 21.2%	30 15.9%
Asian	1 2%	0 0%	8 16.3%	0 0%	9 4.8%
Region of Enrollment (participants) [Number]
United States	51 100%	56 100%	49 100%	33 100%	189 100%

Outcome Measures

1. Primary Outcome

Title	HAM-D 17 Item: Hamilton Depression Rating Scale
Description	Hamilton depression rating scale (17-item HAM-D): Scores can range from 0 to 52: No depression (0-7); Mild depression (8-16); Moderate depression (17-23); and Severe depression (≥24).
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	High Risk Depression	Low Risk Depression	Healthy Control	Bipolar
Arm/Group Description	Interventions will include the prescribing of Selective serotonin reuptake inhibitor or Serotonin-norepinephrine reuptake inhibitor antidepressants, bupropion or other antidepressant. Selective Serotonin Reuptake Inhibitor (SSRI): Subjects with depression will be treated with a Selective Serotonin Reuptake Inhibitor (SSRI) or a Serotonin-norepinephrine reuptake inhibitor (SNRI) for 24 months.	Interventions will include the prescribing of Selective serotonin reuptake inhibitor or Serotonin-norepinephrine reuptake inhibitor antidepressants, bupropion or other antidepressant.. Selective Serotonin Reuptake Inhibitor (SSRI): Subjects with depression will be treated with a Selective Serotonin Reuptake Inhibitor (SSRI) or a Serotonin-norepinephrine reuptake inhibitor (SNRI) for 24 months.	There is no intervention, but rather phone follow ups conducted as check ins to determine the continued eligibility of the healthy control participant.	Bipolar participants are checked in with via phone conversations every three months, and have the opportunity to be scheduled for non-study visits to manage their symptoms.
Measure Participants	15	11	6	4
Mean (Standard Deviation) [score on a scale]	6.6 (6.62)	4.91 (4.11)	2.333 (2.732)	3.75 (4.992)

2. Secondary Outcome

Title	YMRS: Young Mania Rating Scale
Description	Young Mania Rating Scale: Scores can range from 0 to 60: In Remission/No Mania (0-8); Mild (9-12); Moderate (13-18); Severe (19-25); Very Severe (>25)
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	High Risk Depression	Low Risk Depression	Healthy Control	Bipolar
Arm/Group Description	Interventions will include the prescribing of Selective serotonin reuptake inhibitor or Serotonin-norepinephrine reuptake inhibitor antidepressants, bupropion or other antidepressant. Selective Serotonin Reuptake Inhibitor (SSRI): Subjects with depression will be treated with a Selective Serotonin Reuptake Inhibitor (SSRI) or a Serotonin-norepinephrine reuptake inhibitor (SNRI) for 24 months.	Interventions will include the prescribing of Selective serotonin reuptake inhibitor or Serotonin-norepinephrine reuptake inhibitor antidepressants, bupropion or other antidepressant.. Selective Serotonin Reuptake Inhibitor (SSRI): Subjects with depression will be treated with a Selective Serotonin Reuptake Inhibitor (SSRI) or a Serotonin-norepinephrine reuptake inhibitor (SNRI) for 24 months.	There is no intervention, but rather phone follow ups conducted as check ins to determine the continued eligibility of the healthy control participant.	Bipolar participants are checked in with via phone conversations every three months, and have the opportunity to be scheduled for non-study visits to manage their symptoms.
Measure Participants	15	11	6	4
Mean (Standard Deviation) [score on a scale]	0.2 (0.561)	0 (0)	0 (0)	1.75 (3.5)

Adverse Events

Time Frame	24 months
Arm/Group Title	High Risk Depression		Low Risk Depression		Healthy Control		Bipolar
Arm/Group Description	Interventions will include the prescribing of Selective serotonin reuptake inhibitor or Serotonin-norepinephrine reuptake inhibitor antidepressants, bupropion or other antidepressant. Selective Serotonin Reuptake Inhibitor (SSRI): Subjects with depression will be treated with a Selective Serotonin Reuptake Inhibitor (SSRI) or a Serotonin-norepinephrine reuptake inhibitor (SNRI) for 24 months.		Interventions will include the prescribing of Selective serotonin reuptake inhibitor or Serotonin-norepinephrine reuptake inhibitor antidepressants, bupropion or other antidepressant.. Selective Serotonin Reuptake Inhibitor (SSRI): Subjects with depression will be treated with a Selective Serotonin Reuptake Inhibitor (SSRI) or a Serotonin-norepinephrine reuptake inhibitor (SNRI) for 24 months.		There is no intervention, but rather phone follow ups conducted as check ins to determine the continued eligibility of the healthy control participant.		Bipolar participants are checked in with via phone conversations every three months, and have the opportunity to be scheduled for non-study visits to manage their symptoms.
All Cause Mortality
	High Risk Depression		Low Risk Depression		Healthy Control		Bipolar
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/51 (0%)		0/56 (0%)		0/49 (0%)		0/33 (0%)
Serious Adverse Events
	High Risk Depression		Low Risk Depression		Healthy Control		Bipolar
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/51 (9.8%)		3/56 (5.4%)		0/49 (0%)		0/33 (0%)
Psychiatric disorders
Sucidial Ideation	3/51 (5.9%)		2/56 (3.6%)		0/49 (0%)		0/33 (0%)
Hospitalization	1/51 (2%)		1/56 (1.8%)		0/49 (0%)		0/33 (0%)
Suicide Attempt	1/51 (2%)		0/56 (0%)		0/49 (0%)		0/33 (0%)
Other (Not Including Serious) Adverse Events
	High Risk Depression		Low Risk Depression		Healthy Control		Bipolar
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/51 (5.9%)		4/56 (7.1%)		0/49 (0%)		0/33 (0%)
Pregnancy, puerperium and perinatal conditions
Pregnancy	2/51 (3.9%)		1/56 (1.8%)		0/49 (0%)		0/33 (0%)
Psychiatric disorders
Substance Abuse Treatment	0/51 (0%)		2/56 (3.6%)		0/49 (0%)		0/33 (0%)
Social circumstances
Visit to Emergency Room	1/51 (2%)		1/56 (1.8%)		0/49 (0%)		0/33 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.