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Fluoxetine vs CBT in Childhood Anxiety Disorders (SMART)

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ClinicalTrials.gov Identifier: NCT04760275
Recruitment Status : Recruiting
First Posted : February 18, 2021
Last Update Posted : February 18, 2021
Sponsor:
Collaborator:
Patient-Centered Outcomes Research Institute
Information provided by (Responsible Party):
Bradley Peterson, Children's Hospital Los Angeles

Brief Summary:

Treatment of every child with anxiety disorder begins with the question of which treatment to start first. Both fluoxetine and CBT have strong empirical support, but few studies have compared their initial effectiveness head-to-head, and none has investigated what to do if the treatment tried first isn't working well-whether to optimize the treatment already begun or to add the other treatment.

Aims of the study:

  1. The study will assess whether beginning with Cognitive Behavioral Therapy (CBT) or fluoxetine medication is more effective in improving youth-rated anxiety symptoms over the 24-week intervention
  2. If the initial intervention fails to induce clinical remission by week 12, the study will assess whether optimizing the initial treatment modality alone, or adding the other modality to the first, yields better symptom improvement by week 24
  3. The study will assess whether one sequence of treatment modalities - i.e., CBT followed by optimized CBT; CBT followed by optimized CBT+ medication; medication followed by optimized medication; medication followed by optimized medication + CBT -- is significantly better or worse than predicted from the two main effects
  4. The study will assess the stability of treatment response for ≥12 months following completion of the 24-week trial

Condition or disease Intervention/treatment Phase
Anxiety Disorders Drug: Fluoxetine Behavioral: Cognitive Behavioral Therapy (CBT) Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 404 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Sequential Multiple Assignment Randomized Trial (SMART) Assessing Medication and CBT Sequencing Strategies in the Treatment of Predominantly Ethnic Minority, Underserved Youth With Anxiety Disorders
Actual Study Start Date : February 10, 2021
Estimated Primary Completion Date : September 1, 2024
Estimated Study Completion Date : September 1, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Anxiety
Drug Information available for: Fluoxetine

Arm Intervention/treatment
Active Comparator: Medication - Fluoxetine

Approved medication by the U.S. Food and Drug Administration (FDA) for treating anxiety disorders in children.

The study's starting dose, and minimum permitted, will be 10 mg/day; should that not be tolerated, the patient will be withdrawn from active treatment (but not from study follow-up). After 1 week at 10 mg/day, the dose will increase to 20 mg/day. After completion of week 4, 10 mg/day dose increases will be permitted every other week as tolerated, up to a maximum daily dose of 80 mg/day. If patients are on doses >20mg/day, the total daily dose can be prescribed either once daily or split into twice daily administrations.

Drug: Fluoxetine

This will be a single-blind SMART design of 24 weeks duration that will employ two sequential levels of randomization, one in each of two 12-week stages of the study.

In Stage 1, participants will be randomized 1:1 to receive 12 weeks of the medication fluoxetine in upward-titrated dosages. In Stage 2, also 12 weeks in duration, participants who remit during the first 12 weeks of treatment will continue maintenance-level therapy with fluoxetine. All participants who do not remit will be randomized (1:1) to either (1) optimization of fluoxetine (increasing the dose of fluoxetine as tolerated), or (2) optimization of fluoxetine and addition of Cognitive Behavioral Therapy (CBT).


Active Comparator: Cognitive Behavioral Therapy (CBT)

Type of talk therapy that aims to identify and replace negative thoughts, using positive behavioral skills to create and maintain positive moods and healthy relationships.

The Coping Cat (CC) program will be used as the behavioral intervention for this study.CC is an established evidence-based CBT treatment for pediatric anxiety. It is delivered in individual therapy sessions with anxious children.

Behavioral: Cognitive Behavioral Therapy (CBT)

This will be a single-blind SMART design of 24 weeks duration that will employ two sequential levels of randomization, one in each of two 12-week stages of the study.

In Stage 1, participants will be randomized 1:1 to receive 12 weeks of weekly CBT implemented with Coping Cat (CC). In Stage 2, also 12 weeks in duration, participants who remit during the first 12 weeks of treatment will continue maintenance-level therapy with CBT. All participants who do not remit will be randomized (1:1) to either (1) optimization of CBT (intensifying exposure practice and skills review), or (2) optimization of CBT and addition of the medication fluoxetine.





Primary Outcome Measures :
  1. Youth - SCARED (Screen for Child Anxiety Related Disorders) [ Time Frame: Week 24 ]
    Patient ratings of anxiety symptom severity. Possible range of scores is 0-82, with higher scores indicating greater severity.


Secondary Outcome Measures :
  1. Parent - SCARED (Screen for Child Anxiety Related Disorders) [ Time Frame: Week 24 ]
    Parent ratings of anxiety symptom severity. Possible range of scores is 0-82, with higher scores indicating greater severity.

  2. Youth - Child Anxiety Impact Scale (CAIS) [ Time Frame: Week 24 ]
    Patient ratings of anxiety functional impairment. Possible range of scores is 0-81, with higher scores indicating greater impact.

  3. Parent - Child Anxiety Impact Scale (CAIS) [ Time Frame: Week 24 ]
    Parent ratings of anxiety functional impairment. Possible range of scores is 0-81, with higher scores indicating greater impact.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   8 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients ages 8-17.
  2. Patients screening positive (score ≥3) on the SCARED-5 (possible range 0-10, higher scores indicate greater severity) and positive (score ≥25) on the SCARED-41 (possible range 0-82, higher scores indicate greater severity).
  3. Patients with an anxiety disorder (generalized anxiety, separation anxiety, panic, or social anxiety) on the Schedule for Affective Disorders and Schizophrenia for School-Aged Children (K-SADS).
  4. Patients with a score of >8 on the Child Anxiety Impact Scale (CAIS- possible range of scores is 0-81, higher scores indicate greater impact) representing at least moderately severe illness.
  5. Patients and at least one parent/caregiver of all ages, who are fluent in either English or Spanish.
  6. Patient and their parent agree for the child to be randomized to either fluoxetine or CBT.

Exclusion Criteria:

  1. Patients with a neurological disorder or unstable medical condition, as determined by medical chart and medical history review by the site director and PI.
  2. Females who are pregnant or sexually active but not using an effective method of birth control (potential adverse fetal effects of medication).
  3. Patients with any of the following characteristics/conditions on the Columbia-Suicide Severity Rating Scale (CSSRS- possible range of scores 0-5, higher scores representing greater severity):

    1. Patients scoring a 3 AND access to crisis level support is unavailable OR
    2. Patients scoring a 4 if frequency, duration, and deterrent all = 1 AND treatment in a specialty mental health clinic is not available OR
    3. Patients scoring a 4 if frequency, duration, OR deterrents are > 1
    4. Patients scoring a 5
  4. Due to the cognitive and socio-emotional demands of the CBT protocol, we will exclude youths who are likely to be functioning at a developmental level outside the minimum age for the treatment manual (age 8): Youths who are placed outside of a general education (GE) classroom for > 50% of the school day or require a one-on-one classroom aide to maintain placement in a GE class, or are performing academically below the 3rd grade level in reading and language arts.
  5. Patients with a current obsessive-compulsive disorder (OCD) diagnosis, for which this study's treatments would be inappropriate clinically and ethically, on the KSADS.
  6. Patients with a current post-traumatic stress disorder (PTSD) diagnosis, for which this study's treatments would be inappropriate clinically and ethically, with the following characteristics/conditions on the Child Trauma Screen (CTS):

    a. Patients scoring at least 1 past trauma on the events portion of the screener AND a parent reaction score ≥10 (possible range of scores 0-18, with higher scores representing more severe reactions).

  7. Patients currently receiving a selective serotonin reuptake inhibitor (SSRI), serotonin-norepinephrine reuptake inhibitor (SNRI), or benzodiazepine.
  8. Patients who have taken Monoamine Oxidase Inhibitors (MAOIs), Pimozide, Thioridazine, Olanzapine, Tricyclic Antidepressants (TCAs), Antipsychotics such as Haloperidol and Clozapine, Anticonvulsants such as Phenytoin and Carbamazepine within 2 weeks prior to starting the study.
  9. Patients currently in foster care.

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): NCT04760275


Contacts
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Contact: Courtney Allem 323-361-1435 callem@chla.usc.edu
Contact: Titi Towolawi 323-361-6496 ttowolawi@chla.usc.edu

Locations
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United States, California
Children's Hospital Los Angeles Recruiting
Los Angeles, California, United States, 90027
Contact: Courtney Allem    323-361-1435    callem@chla.usc.edu   
Contact: Titi Towolawi    323-361-6496    ttowolawi@chla.usc.edu   
Principal Investigator: Bradley S. Peterson, MD         
Sponsors and Collaborators
Children's Hospital Los Angeles
Patient-Centered Outcomes Research Institute
Investigators
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Principal Investigator: Bradley S. Peterson, MD Children's Hospital Los Angeles
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Bradley Peterson, Principal Investigator, Children's Hospital Los Angeles
ClinicalTrials.gov Identifier: NCT04760275    
Other Study ID Numbers: CHLA-19-00478
First Posted: February 18, 2021    Key Record Dates
Last Update Posted: February 18, 2021
Last Verified: February 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Anxiety Disorders
Mental Disorders
Fluoxetine
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