Clinical trial NCT02189213: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Generalized Anxiety Disorder
Separation Anxiety Disorder
Social Phobia
Keywords: anxiety
SSRI
biomarker
sleep
children
adolescents
young adults
Lead sponsor: New York State Psychiatric Institute
Sponsor class: OTHER
Collaborators: name: Columbia University
First posted: 2014-07-14
Enrollment: 14
Sex: ALL
Minimum age (years): 8
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

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.

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.

Primary outcomes:
measure: Clinical Global Impression-Improvement (CGI-I) Score
timeFrame: Final visit, at 12 weeks of treatment
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: NYSPI
state: New York
Study officials:
affiliation: New York State Psychiatric Institue
name: Amir Levine
role: PRINCIPAL_INVESTIGATOR
References: