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

• ClinicalTrials.gov Identifier: NCT02189213
• Recruitment Status: Terminated
• First Posted: July 14, 2014
• Results First Posted: October 11, 2021
• Last Update Posted: October 11, 2021
• Sponsor: New York State Psychiatric Institute
• Collaborator: Columbia University
• Information provided by (Responsible Party): Amir A. Levine, New York State Psychiatric Institute

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Generalized Anxiety Disorder; Separation Anxiety Disorder; Social Phobia	Drug: Sertraline	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 14 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Treatment of Pediatric Anxiety Disorders by Predicting Treatment Response Through Biocellular Markers and Sleep
• Actual Study Start Date: July 2014
• Actual Primary Completion Date: December 2019
• Actual Study Completion Date: December 2019

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Sertraline; Sertraline will be administered PO to treat anxiety disorders in children and adolescents. he following dosing schedules will be used: Sertraline will be titrated from 25mg once a day orally up to 200mg 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.	Drug: Sertraline; Sertraline will be administered to treat anxiety disorders in children and adolescents.; Other Name: Zoloft
No Intervention: Control; There will be no intervention in this arm.

Outcome Measures

Primary Outcome Measures :

1. Clinical Global Impression-Improvement (CGI-I) Score [ Time Frame: Final visit, at 12 weeks of treatment ]

   The CGI-I score at the final visit will determine treatment response.

   The CGI-Improvement scale comprises a one-item measures evaluating the following change from the initiation of treatment on a seven-point scale.

   The following one query is rated on a seven-point scale: "Compared to the patient's condition at admission to the project [prior to medication initiation], this patient's condition is: 1=very much improved since the initiation of treatment; 2=much improved; 3=minimally improved; 4=no change from baseline (the initiation of treatment); 5=minimally worse; 6= much worse; 7=very much worse since the initiation of treatment.

   CGI-I scale of 1-2 is considered response to treatment. Anything below that is considered non-response to sertraline treatment.

Eligibility Criteria

• Ages Eligible for Study: 8 Years to 25 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

United States, New York

NYSPI

New York, New York, United States, 10032

Sponsors and Collaborators

New York State Psychiatric Institute

Columbia University

Investigators

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

  Study Documents (Full-Text)

Documents provided by Amir A. Levine, New York State Psychiatric Institute:

Study Protocol  [PDF] May 15, 2020

Statistical Analysis Plan  [PDF] August 30, 2021

More Information

• Responsible Party: Amir A. Levine, Psychiatrist 2/Associate Professor of Clinical Psychiatry, New York State Psychiatric Institute
• ClinicalTrials.gov Identifier: NCT02189213
• Other Study ID Numbers: 6884
• First Posted: July 14, 2014
• Results First Posted: October 11, 2021
• Last Update Posted: October 11, 2021
• Last Verified: September 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Amir A. Levine, New York State Psychiatric Institute:

anxiety; SSRI; biomarker; sleep; children; adolescents; young adults

Additional relevant MeSH terms:

Disease; Anxiety Disorders; Phobia, Social; Anxiety, Separation; Pathologic Processes; Mental Disorders; Phobic Disorders; Neurodevelopmental Disorders; Sertraline; Antidepressive Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Serotonin Agents; Physiological Effects of Drugs