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

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ClinicalTrials.gov Identifier: NCT02473250
Recruitment Status : Recruiting
First Posted : June 16, 2015
Last Update Posted : November 5, 2018
Sponsor:
Information provided by (Responsible Party):
Martin Lan, New York State Psychiatric Institute

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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
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 : January 2015
Estimated Primary Completion Date : September 2019
Estimated Study Completion Date : September 2019


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 Name: 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 Name: Celexa




Primary Outcome Measures :
  1. Montgomery-Asberg Depression Rating Scale [ Time Frame: 6 weeks ]

Secondary Outcome Measures :
  1. Hamilton Anxiety Rating Scale [ Time Frame: 6 weeks ]
  2. Young Mania Rating Scale [ Time Frame: 6 weeks ]
  3. Clinical Global Impression-1 [ Time Frame: 6 weeks ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02473250


Contacts
Contact: Martin Lan, MD PhD 646 774 7610 martin.lan@nyspi.columbia.edu

Locations
United States, New York
New York State Psychiatric Institute/Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Contact: Martin Lan, MD PHD    646-774-7610    martin.lan@NYSPI.COLUMBIA.EDU   
Sponsors and Collaborators
New York State Psychiatric Institute
Investigators
Principal Investigator: Martin Lan, MD PHD Columbia University

Additional Information:
Responsible Party: Martin Lan, Clinical Psychiatrist, New York State Psychiatric Institute
ClinicalTrials.gov Identifier: NCT02473250     History of Changes
Other Study ID Numbers: #7056
First Posted: June 16, 2015    Key Record Dates
Last Update Posted: November 5, 2018
Last Verified: November 2018

Additional relevant MeSH terms:
Disease
Bipolar Disorder
Pathologic Processes
Bipolar and Related Disorders
Mental Disorders
Fluoxetine
Citalopram
Valproic Acid
Serotonin
Dexetimide
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Serotonin Agents
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Cytochrome P-450 CYP2D6 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Serotonin Receptor Agonists
Antiparkinson Agents
Anti-Dyskinesia Agents
Parasympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Muscarinic Antagonists