Treatment of Pediatric Anxiety Disorders by Predicting Treatment Response Through Biocellular Markers and Sleep

• ClinicalTrials.gov Identifier: NCT02189213
• Recruitment Status: Active, not recruiting
• First Posted: July 14, 2014
• Last Update Posted: January 31, 2020
• Sponsor: New York State Psychiatric Institute
• Collaborator: Columbia University
• Information provided by (Responsible Party): Amir A. Levine, New York State Psychiatric Institute

Tracking Information

• First Submitted Date: July 7, 2014
• First Posted Date: July 14, 2014
• Last Update Posted Date: January 31, 2020
• Actual Study Start Date: July 2014
• Actual Primary Completion Date: December 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 20, 2017)

Clinical Global Impression-Improvement (CGI-I) Score [ Time Frame: 12 weeks ]

The CGI-I score at the final visit (week 12) will determine treatment response.

• Original Primary Outcome Measures (submitted: July 11, 2014): RNA expression levels [ Time Frame: 12 weeks ]
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Treatment of Pediatric Anxiety Disorders by Predicting Treatment Response Through Biocellular Markers and Sleep
• Official Title: Treatment of Pediatric Anxiety Disorders by Predicting Treatment Response Through Biocellular Markers and Sleep
• Brief Summary: 1 out of 8 children, adolescents, and young adults suffer from an anxiety disorder. Studies over the past decade show that selective serotonin-reuptake inhibitors (SSRIs), a class of medication that treats anxiety in adults, also works well in young adults, children, and adolescents with anxiety disorders, but only for about 50%. 50% will have undergone treatment for several months before it will be established that the medication is not working to treat the anxiety. The purpose of this study is to find a test that will predict treatment outcome from the beginning based on behavioral and biological measures.
• Detailed Description: Current evidence based psychiatric treatment for child, adolescent, and young adult anxiety disorders involves a trial and error process. Pediatric psychiatrists start with the first line treatments (i.e. SSRI or psychotherapy), which requires from 4-8 weeks to work. There is a long interval between treatment initiation and response with only 50 to 60% likelihood that the treatment chosen will succeed in reducing anxiety symptoms. The science that will enable us to predict who will respond to medication treatment does not exist. Studies have demonstrated a correlation between cellular markers in white blood cells and psychiatric disorders suggesting that certain genes may also change their expression in peripheral cells in response to treatment of psychiatric disorders. Several studies report a significant decrease in expression of key genes that are involved in the pathophysiology of anxiety and depression in the brain, such as BDNF, CREB and HDAC5 levels in leukocytes of people with mood and anxiety disorders. The levels of BDNF, HDAC5 and CREB in white blood cells then respond to treatment and match that of controls after treatment with SSRIs. The increased accessibility to sequencing technology allows us to survey many more potential biomarkers than what was possible just several years ago. This may enable us to formulate a test that will predict, based on biocellular markers, treatment outcome in anxiety disorders for children, adolescents, and young adults before the onset of treatment. By finding molecular markers that can predict treatment success from the onset, the investigators can improve treatment outcomes considerably compared to current standard treatment practices. This kind of personalized medicine is the future of psychiatry.
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Diagnostic

Condition

• Generalized Anxiety Disorder
• Separation Anxiety Disorder
• Social Phobia

Intervention

• Drug: Sertraline
  Sertraline will be administered to treat anxiety disorders in children and adolescents.
  Other Name: Zoloft
• Drug: Fluoxetine
  Fluoxetine will be administered to treat anxiety disorders in children and adolescents.
  Other Name: Prozac
• Drug: Escitalopram
  Lexapro will be administered to treat anxiety disorders in children and adolescents.
  Other Name: Lexapro

Study Arms

• Active Comparator: Sertraline, Fluoxetine, or Escitalopram

  Sertraline, Fluoxetine, or Escitalopram will be administered PO to treat anxiety disorders in children and adolescents. One of the following dosing schedules will be used:

  1. Sertraline will be titrated from 25mg once a day orally up to 200mg once a day orally, for 12 weeks, or
  2. Fluoxetine will be titrated from 10mg once a day orally up to 40mg once a day orally, for 12 weeks or
  3. Escitalopram will be titrated from 10mg once a day orally up to 40mg once a day orally, for 12 weeks.

  The titration will stop at the dose in which the participant shows a full response to the medication or experiences side effects that will inhibit titration.

  Interventions:

  • Drug: Sertraline
  • Drug: Fluoxetine
  • Drug: Escitalopram
• No Intervention: Control
  There will be no intervention in this arm.

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: July 11, 2014): 60
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2020
• Actual Primary Completion Date: December 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Participants aged 8-25 years inclusive at the time of the consent/assent, either outpatient or inpatient if hospitalization is required for one of the following reasons:

   • It is presently unsafe for subject to stay at home because he/she may run away
   • Subject needs closer monitoring while being started on medications
   • Subject needs a level of care that is greater than once a week outpatient treatment and is willing to participate in the study.
2. Participant's parent or legally authorized representative (LAR) must provide signature of informed consent, and there must be documentation of assent by the participant.
3. Participant meets Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) or Fifth Edition (DSM-V) criteria for a clinically impairing anxiety disorder based on detailed psychiatric evaluation at screening including completion of the Anxiety Disorders Interview Schedule for DSM-IV or DSM-V Child Version (ADIS-C) and a Children's Global Assessment Scale (CGAS) score less than 65.

4. Participants who are female of child-bearing potential (defined as ≥9 years of age or if <9 years of age are post-menarchal) must have a negative urine pregnancy test at the Baseline Visit. Females of child-bearing potential must abstain from sexual activity that could result in pregnancy or agree to use acceptable methods of contraception. Condoms should be used with the following acceptable contraceptives:

   • Intrauterine devices,
   • Hormonal contraceptives (oral, depot, patch, injectable, or vaginal ring).
   • Other acceptable contraceptive methods are double barrier methods (e.g., condoms and diaphragms with spermicidal gel or foam).

Exclusion Criteria:

1. Participant has a current co-morbid psychiatric diagnosis of bipolar disorder, psychosis, a pervasive developmental disorder other than Asperger's Syndrome, an eating disorder, substance abuse disorder, or a sleep disorder of narcolepsy and/or sleep apnea.
2. Participant has any condition or illness which, in the opinion of the study doctor, represents as an inappropriate risk to the participant and/or could confound the interpretation of the study.
3. Participant has received any evidence-based psychosocial intervention in the past 6 weeks i.e. Individual Cognitive Behavioral Therapy, Group Cognitive Behavioral Therapy, or Social Effectiveness Training.
4. Participant is unwilling or unable to provide blood, urine, and/or saliva samples at designated visits.
5. Participant is female and is pregnant or is currently lactating.
6. Participant is currently considered at risk for suicide in the opinion of the study doctor, has made a suicide attempt within the past 6 months, or is currently reporting active suicidal ideation. Participants with intermittent passive suicidal ideation are not necessarily excluded based on the assessment of the study doctor. Control participants with any suicidal ideation will not be eligible for the study.
7. Participant has had a substance use disorder within the past 6 months.
8. Participant has a clinically important abnormality on drug and alcohol screen.
9. Participant has started or changed the dosage of medication (including herbal supplements) that has anxiolytic, anxiogenic, or central nervous system (CNS) effects within the past 3 months.
10. Participant has a known or suspected allergy, hypersensitivity, or clinically significant intolerance to any components found in the study drug.
11. Participant has had several failed attempts with SSRI treatment.
12. Participant has an acute illness and/or is taking short term medication at the time of initiation of the study.
13. Participant failed screening or was previously enrolled in this study
14. Participant is unable to read.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 8 Years to 25 Years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02189213
• Other Study ID Numbers: 6884
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Amir A. Levine, New York State Psychiatric Institute
• Study Sponsor: New York State Psychiatric Institute
• Collaborators: Columbia University

Investigators

• Principal Investigator: Amir Levine; New York State Psychiatric Institue

• PRS Account: New York State Psychiatric Institute
• Verification Date: January 2020