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Differentiating Unipolar and Bipolar Depression in Young Adults Using fMRI

Primary Purpose

Bipolar Disorder, Major Depression

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Selective Serotonin Reuptake Inhibitor (SSRI)
Sponsored by
The Cleveland Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Bipolar Disorder focused on measuring Bipolar, Depression, Mania, Hypomania, fMRI, antidepressant

Eligibility Criteria

15 Years - 30 Years (Child, Adult)All SexesAccepts Healthy Volunteers

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 - i. 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 - i. 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.

Sites / Locations

  • Cleveland Clinic Foundation Center for Behavioral Health

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

No Intervention

No Intervention

Arm Label

High Risk Depression

Low Risk Depression

Healthy Control

Bipolar

Arm Description

Interventions will include the prescribing of Selective serotonin reuptake inhibitor or Serotonin-norepinephrine reuptake inhibitor antidepressants, bupropion or other antidepressant.

Interventions will include the prescribing of Selective serotonin reuptake inhibitor or Serotonin-norepinephrine reuptake inhibitor antidepressants, bupropion or other antidepressant..

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.

Outcomes

Primary Outcome Measures

HAM-D 17 Item: Hamilton Depression Rating Scale
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

YMRS: Young Mania Rating Scale
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)

Full Information

First Posted
December 12, 2011
Last Updated
November 26, 2019
Sponsor
The Cleveland Clinic
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1. Study Identification

Unique Protocol Identification Number
NCT01811147
Brief Title
Differentiating Unipolar and Bipolar Depression in Young Adults Using fMRI
Official Title
Differentiating Unipolar and Bipolar Depression in Young Adults Using fMRI
Study Type
Interventional

2. Study Status

Record Verification Date
November 2019
Overall Recruitment Status
Completed
Study Start Date
November 2011 (undefined)
Primary Completion Date
June 2018 (Actual)
Study Completion Date
June 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The Cleveland Clinic

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bipolar Disorder, Major Depression
Keywords
Bipolar, Depression, Mania, Hypomania, fMRI, antidepressant

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
192 (Actual)

8. Arms, Groups, and Interventions

Arm Title
High Risk Depression
Arm Type
Experimental
Arm Description
Interventions will include the prescribing of Selective serotonin reuptake inhibitor or Serotonin-norepinephrine reuptake inhibitor antidepressants, bupropion or other antidepressant.
Arm Title
Low Risk Depression
Arm Type
Experimental
Arm Description
Interventions will include the prescribing of Selective serotonin reuptake inhibitor or Serotonin-norepinephrine reuptake inhibitor antidepressants, bupropion or other antidepressant..
Arm Title
Healthy Control
Arm Type
No Intervention
Arm Description
There is no intervention, but rather phone follow ups conducted as check ins to determine the continued eligibility of the healthy control participant.
Arm Title
Bipolar
Arm Type
No Intervention
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Selective Serotonin Reuptake Inhibitor (SSRI)
Other Intervention Name(s)
Serotonin-norepinephrine reuptake inhibitor
Intervention Description
Subjects with depression will be treated with a Selective Serotonin Reuptake Inhibitor (SSRI) or a Serotonin-norepinephrine reuptake inhibitor (SNRI) for 24 months.
Primary Outcome Measure Information:
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
Secondary Outcome Measure Information:
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
15 Years
Maximum Age & Unit of Time
30 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
INCLUSION CRITERIA FOR BIPOLAR DEPRESSED PATIENTS: Ages 15 - 30 years (inclusive) and able to give voluntary informed consent (parents must also sign consent for subjects under 18) Satisfy criteria for Diagnostic and Statistical Manual 4th edition (DSM-IV-TR) for Bipolar I or II disorder Satisfy criteria for DSM-IV depressive episode-current 17-item Hamilton Depression Rating Scale > 15 but < 25; Young Mania Rating Scale score < 10 Satisfy criteria to undergo an MRI scan based on MRI screening questionnaire. Able to be managed as outpatients during the study as ascertained by the following - i. 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: Ages 15 - 30 years and able to give voluntary informed consent (Parental consent must also be obtained for those under 18 years old). Satisfy criteria for DSM-IV-TR Major Depressive Episode using a Structured Interview Never met criteria for mania or hypomania 17-item Hamilton Depression Rating Scale score (HDRS) > 15 and < 25. Young Mania Rating Scale (YMRS) score < 10 Satisfy safety criteria to undergo an MRI scan Able to be managed as outpatients during the study as ascertained by the following - i. 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: Family history of bipolar disorder in at least one first degree relative History of any sub-threshold hypomania symptoms History of mood episode related psychotic symptoms ADDITIONAL INCLUSION CRITERIA FOR LOW RISK UD (HRUD) PATIENTS BESIDE THE INCLUSION CRITERIA FOR UD: No family history of BD in a first or a second degree relative No past history of any sub-threshold hypomania symptoms No history of psychotic symptoms EXCLUSION CRITERIA FOR DEPRESSION AND BIPOLAR SUBJECTS: Meeting DSM-IV criteria for schizophrenia, schizophreniform disorder, schizoaffective disorder, mental retardation, pervasive developmental disorder. History of receiving electroconvulsive therapy in the past 1 year Use of neuroleptics, mood stabilizers or benzodiazepines in the past 2 weeks. Use of antidepressants in the past 2 weeks. If on fluoxetine in the past, then should not have been on this medication for 5 weeks. Acutely suicidal or homicidal or requiring inpatient treatment. 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. Use of alcohol in the past 1 week before the MRI scan. 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. Current pregnancy or breast feeding. Metallic implants or other contraindication to MRI. INCLUSION CRITERIA FOR HEALTHY CONTROLS: Healthy subjects matched for age, gender and ethnicity will be included Ages 15 - 30 years (inclusive) and able to give voluntary informed consent (Parental consent must also be obtained for those under 18 years old) No current or past history of psychiatric illness or substance abuse or dependence. No current or past history of psychiatric illness or substance abuse or dependence in a first degree relative. EXCLUSION CRITERIA FOR HEALTHY CONTROLS: Pregnant or breast feeding. Metallic implants or other contraindication to MRI. Significant family history of psychiatric or neurological illness. Currently taking any prescription or centrally acting medications. Serious acute or chronic medical or neurological illness as assessed by history, physical examination and laboratory examination including CBC and blood chemistry. Use of alcohol in the past 1 week and not being able to avoid alcohol use during the course of the study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Amit Anand, MD
Organizational Affiliation
The Cleveland Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cleveland Clinic Foundation Center for Behavioral Health
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
30579045
Citation
Koirala P, Hu B, Altinay M, Li M, DiVita AL, Bryant KA, Karne HS, Fiedorowicz JG, Anand A. Sub-threshold bipolar disorder in medication-free young subjects with major depression: Clinical characteristics and antidepressant treatment response. J Psychiatr Res. 2019 Mar;110:1-8. doi: 10.1016/j.jpsychires.2018.12.006. Epub 2018 Dec 8.
Results Reference
derived

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Differentiating Unipolar and Bipolar Depression in Young Adults Using fMRI

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