Prediction of Clinical Response to SSRI Treatment in Bipolar Disorder Using Serotonin 1A Receptor PET Imaging

• Sponsor: New York State Psychiatric Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT02473250
• Collaborator: (none)
• Enrollment: 40
• Location: 1
• Arm: 1
• Duration (Months): 59
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

This study is for subjects with a diagnosis of bipolar disorder who have depression at the time of recruitment. It involves brain imaging with an MRI (magnetic resonance imaging) and PET scan (positron emission tomography) and treatment with an antidepressant. The medication involves adding an SSRI (either celexa/citalopram or prozac/fluoxetine) to a mood stabilizer.

Condition or Disease	Intervention/Treatment	Phase
Bipolar Disorder	Drug: Fluoxetine; Drug: Citalopram	Phase 4

Detailed Description

Bipolar disorder is associated with alterations of chemicals in the brain, including one named serotonin. Treatment of depression in bipolar disorder can be accomplished by increasing serotonin function by medications named selective serotonin reuptake inhibitors (SSRI's). Serotonin signals in the brain occur through receptors in a way that is similar to a lock and key, where serotonin is a key and the receptor is a lock. One important receptor is the serotonin 1A (5-HT1A) receptor. This receptor has been found to be abnormal in bipolar disorder during periods of depression, as measured by a type of brain imaging called positron emission tomography (PET). The amount of brain 5-HT1A receptor measured by imaging has also been associated with how well depressed patients with major depressive disorder respond to an SSRI medication. This project will measure the 5-HT1A receptors in bipolar depressed individuals using PET with the radiotracer [11C]-CUMI-101 and will evaluate the ability of this brain imaging signal to predict how patients respond to SSRI treatment when added to a mood stabilizer.

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Prediction of Clinical Response to SSRI Treatment in Bipolar Disorder Using Serotonin 1A Receptor PET Imaging
• Study Start Date: Jan 1, 2015
• Actual Primary Completion Date: Dec 1, 2019
• Actual Study Completion Date: Dec 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Bipolar depressed Bipolar depressed subjects will have neuroimaging and treatment with fluoxetine in combination with a mood stabilizer (valproate)	Drug: Fluoxetine; Bipolar depressed patients will be treated with fluoxetine in combination with a mood stabilizer (valproate).; Other Names: Prozac ; Drug: Citalopram; Bipolar depressed patients will be treated with citalopram in combination with a mood stabilizer (valproate) if fluoxetine is not clinically warranted.; Other Names: Celexa

Outcome Measures

Primary Outcome Measures

1. Montgomery-Asberg Depression Rating Scale [6 weeks]

   Depression severity. Minimum=0, Maximum=60. Higher numbers correspond to greater depression severity. The percent change between week 0 and the last observation was calculated.

Secondary Outcome Measures

1. Hamilton Anxiety Rating Scale [6 weeks]

   Anxiety severity. Minimum=0, Maximum=56. The larger the value on the scale, the more intense the anxiety. The percent difference between week 0 and the last observation was calculated.

2. Young Mania Rating Scale [6 weeks]

   Measure of manic symptoms. Minimum=0, Maximum=60. The higher the value on the scale, the more intense the manic symptoms. The maximum value of YMRS over the six week clinical trial is reported.

3. Clinical Global Impression-1 [6 weeks]

   General impression of symptoms by clinician. Minimum=1, Maximum=7. The higher value on the scale, the more symptomatic the patient is. The percent difference between week 0 and the last observation was calculated.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Ability to provide informed consent

• Diagnosis of bipolar I disorder or bipolar II disorder and currently meet criteria for a major depressive episode

• Patients who were on psychiatric medication at presentation will have failed that regimen, as defined as not achieving at least partial remission after an adequate dose of medication for at least six weeks.

• Depression of sufficient severity to score at least 16 on the first 17 items of the Hamilton Depression Rating Scale

• Age range 18-60 years

• Females of child-bearing potential must be willing to use an acceptable method of birth control throughout the study.

• Subject agrees to discontinue all psychotropic other than those in the PSF and other types of drugs likely to interact with the 5-HT1A receptors.

• Subject is likely to tolerate medication cross-taper to monotherapy with a mood stabilizer (valproate, lamotrigine or lithium).

Exclusion Criteria:

• Diagnosis of any other major psychiatric disorders such as lifetime schizophrenia, schizoaffective disorder, current psychotic depression or current drug or alcohol abuse (within two months before the study) or recent drug or alcohol dependence (within six months before the study); anorexia nervosa or bulimia nervosa within the last year; IV drug use of ecstasy use more than three times. Meet criteria for a manic episode at the time of screening.

• Previous failed trial of fluoxetine and citalopram by themselves or in combination with an anti-manic agent, defined as at least six weeks of treatment at the dose of 20 mg per day or more. Failure of two trials of any SSRI or SNRI antidepressant medications.

• If the patients are discontinuing medications as part of the washout period or are starting valproate, previous failed trial of mood stabilizer that they will take alone.

• Experienced intolerable side effects of both citalopram and fluoxetine in the past. If the subject is not on medications, intolerable side effects of valproate in the past.

• History of clinical deterioration when any of the medications that the patient is taking at presentation have been discontinued in the past with the exception of any medications that will be continued during the research protocol.

• A first-degree family history of schizophrenia if the subject is less than 33 years old

• Significant active physical illness, including blood dyscrasias, lymphomas, hypersplenism, endocrinopathies, renal failure, chronic obstructive lung disease, autonomic neuropathies, peripheral vascular disease, malignancy

• Actively suicidal, as defined by expressing ideation with a plan for suicide or develops suicidal ideation that requires immediate medication or treatment intervention.

• Pregnancy, abortion or miscarriage in the two months prior to enrollment or plans to conceive during the course of study participation

• Lactating women

• ECT within the past 6 months

• Subjects who endorse a history of prior head trauma and score 1.5 standard deviations below the mean on Trail-making A & B will be excluded from study participation.

• Metal implants, pacemaker, metal prostheses, metal orthodontic appliances or shrapnel in the body

• Current, past or anticipated exposure to radiation, including:

• Having been badged for radiation exposure in the workplace

• Participation in nuclear medicine protocols in the last year. Subjects will be eligible, however, if the injected dose and dosimetry of the radiotracer are known and the cumulative annual exposure of the previous study and this study is lower than the annual limit for research subjects defined by the FDA (21 CFR 361.1)

• History of claustrophobia that would prevent the participation in imaging scans

• Current anticoagulant or anti-platelet treatment other than aspirin

• Obesity with weight >350 lbs or inability to fit into the MRI scanner

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	New York State Psychiatric Institute/Columbia University Medical Center	New York	New York	United States	10032

Sponsors and Collaborators

• New York State Psychiatric Institute

Investigators

• Principal Investigator: Martin Lan, MD PHD, Columbia University

Study Documents (Full-Text)

• Informed Consent Form - Oct 25, 2019
• Study Protocol and Statistical Analysis Plan - Nov 27, 2020

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Martin Lan, Clinical Psychiatrist, New York State Psychiatric Institute
• ClinicalTrials.gov Identifier: NCT02473250
• Other Study ID Numbers: #7056
• First Posted: Jun 16, 2015
• Last Update Posted: Apr 1, 2021
• Last Verified: Mar 1, 2021

• Additional relevant MeSH terms: Bipolar Disorder; Fluoxetine; Citalopram

Study Results

Participant Flow

Arm/Group Title	Bipolar Depressed
Arm/Group Description	Bipolar depressed subjects had neuroimaging and treatment with a selective serotonin reuptake inhibitor in combination with a mood stabilizer. Fluoxetine was offered first, but citalopram was offered as an alternative if fluoxetine was not clinically appropriate.
Period Title: Overall Study
STARTED	40
COMPLETED	20
NOT COMPLETED	20

Baseline Characteristics

Arm/Group Title	Bipolar Depressed
Arm/Group Description	Bipolar depressed subjects had neuroimaging and treatment with a selective serotonin reuptake inhibitor in combination with a mood stabilizer. Fluoxetine was offered first, but citalopram was offered as an alternative if fluoxetine was not clinically appropriate.
Overall Participants	40
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	37.0 (12.2)
Sex: Female, Male (Count of Participants)
Female	24 60%
Male	16 40%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	13 32.5%
Not Hispanic or Latino	27 67.5%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	3 7.5%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	8 20%
White	23 57.5%
More than one race	6 15%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	40 100%

Outcome Measures

1. Primary Outcome

Title	Montgomery-Asberg Depression Rating Scale
Description	Depression severity. Minimum=0, Maximum=60. Higher numbers correspond to greater depression severity. The percent change between week 0 and the last observation was calculated.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bipolar Depressed
Arm/Group Description	Bipolar depressed subjects will have neuroimaging and treatment with fluoxetine in combination with a mood stabilizer (valproate) Fluoxetine: Bipolar depressed patients will be treated with fluoxetine in combination with a mood stabilizer (valproate). Citalopram: Bipolar depressed patients will be treated with citalopram in combination with a mood stabilizer (valproate) if fluoxetine is not clinically warranted.
Measure Participants	20
Mean (Standard Deviation) [Percent change in MADRS from baseline]	39.24 (10.38)

2. Secondary Outcome

Title	Hamilton Anxiety Rating Scale
Description	Anxiety severity. Minimum=0, Maximum=56. The larger the value on the scale, the more intense the anxiety. The percent difference between week 0 and the last observation was calculated.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bipolar Depressed
Arm/Group Description	Bipolar depressed subjects had neuroimaging and treatment with a selective serotonin reuptake inhibitor in combination with a mood stabilizer. Fluoxetine was offered first, but citalopram was offered as an alternative if fluoxetine was not clinically appropriate.
Measure Participants	20
Mean (Standard Deviation) [Percent change in HAMA score]	13.95 (70.38)

3. Secondary Outcome

Title	Young Mania Rating Scale
Description	Measure of manic symptoms. Minimum=0, Maximum=60. The higher the value on the scale, the more intense the manic symptoms. The maximum value of YMRS over the six week clinical trial is reported.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bipolar Depressed
Arm/Group Description	Bipolar depressed subjects will have neuroimaging and treatment with fluoxetine in combination with a mood stabilizer (valproate) Fluoxetine: Bipolar depressed patients will be treated with fluoxetine in combination with a mood stabilizer (valproate). Citalopram: Bipolar depressed patients will be treated with citalopram in combination with a mood stabilizer (valproate) if fluoxetine is not clinically warranted.
Measure Participants	20
Mean (Standard Deviation) [Scores on a scale]	5.75 (2.49)

4. Secondary Outcome

Title	Clinical Global Impression-1
Description	General impression of symptoms by clinician. Minimum=1, Maximum=7. The higher value on the scale, the more symptomatic the patient is. The percent difference between week 0 and the last observation was calculated.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bipolar Depressed
Arm/Group Description	Bipolar depressed subjects will have neuroimaging and treatment with fluoxetine in combination with a mood stabilizer (valproate) Fluoxetine: Bipolar depressed patients will be treated with fluoxetine in combination with a mood stabilizer (valproate). Citalopram: Bipolar depressed patients will be treated with citalopram in combination with a mood stabilizer (valproate) if fluoxetine is not clinically warranted.
Measure Participants	20
Mean (Standard Deviation) [Percent change in CGI score]	27.17 (25.06)

Adverse Events

Time Frame	Adverse event data were collected over the time that the participants were enrolled in the study. This time range varied depending on the research procedures performed. If all research procedures were performed, the participants were enrolled for 11 weeks.
Arm/Group Title	Bipolar Depressed
Arm/Group Description	Bipolar depressed subjects will have neuroimaging and treatment with fluoxetine in combination with a mood stabilizer (valproate) Fluoxetine: Bipolar depressed patients will be treated with fluoxetine in combination with a mood stabilizer (valproate). Citalopram: Bipolar depressed patients will be treated with citalopram in combination with a mood stabilizer (valproate) if fluoxetine is not clinically warranted.
All Cause Mortality
	Bipolar Depressed
	Affected / at Risk (%)	# Events
Total	0/40 (0%)
Serious Adverse Events
	Bipolar Depressed
	Affected / at Risk (%)	# Events
Total	2/40 (5%)
Psychiatric disorders
Psychiatric Hospitalization	2/40 (5%)	2
Other (Not Including Serious) Adverse Events
	Bipolar Depressed
	Affected / at Risk (%)	# Events
Total	0/40 (0%)

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.