Anxiety DisordersPhase 3SMARTNCT04760275
Fluoxetine vs CBT in Childhood Anxiety Disorders
A Phase 3 study testing Fluoxetine and Cognitive Behavioral Therapy (CBT) in people with Anxiety Disorders, run by Children's Hospital Los Angeles at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 8 to 17 years
- Conditions the study is for
- Anxiety Disorders
- What is being tested?
- Fluoxetine and Cognitive Behavioral Therapy (CBT)
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 316 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Feb 2021to Jul 2026
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Patients ages 8-17
- 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).
- 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, computerized version (KSADS-COMP).
- 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.
- Patients and at least one parent/caregiver of all ages, who are fluent in either English or Spanish.
- Patient and their parent agree for the child to be randomized to either fluoxetine or CBT.
Who cannot join
- Patients with a neurological disorder or unstable medical condition, as determined by medical chart and medical history review by the site director and PI.
- Females who are pregnant or sexually active but not using an effective method of birth control (potential adverse fetal effects of medication).
- 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):
- Patients scoring a 3 AND access to crisis level support is unavailable OR
- Patients scoring a 4 if frequency, duration, and deterrent all = 1 AND treatment in a specialty mental health clinic is not available OR
- Patients scoring a 4 if frequency, duration, OR deterrents are > 1
Show all 18Show fewer
- 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 2nd grade level in reading and language arts.
- Patients with a current obsessive-compulsive disorder (OCD) diagnosis, for which this study's treatments would be inappropriate clinically and ethically, on the KSADS-COMP.
- 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) and KSADS-COMP:
- Patients scoring at least 1 past trauma on the events portion of the CTS AND a reaction score ≥10 (possible range of scores 0-18, with higher scores representing more severe reactions) on the parent report.
- Patients currently receiving fluoxetine. Those who are currently receiving any other selective serotonin reuptake inhibitor (SSRI), serotonin-norepinephrine reuptake inhibitor (SNRI), other antidepressant, or benzodiazepine for the treatment of either anxiety or sleep disturbance and who otherwise meet all eligibility requirement will be permitted to taper and discontinue their medication to enter the study if they wish to do so and if they otherwise still meet all eligibility requirements after the taper.
- Psychopharmacologists on the study team will provide guidelines for the medication taper and discontinuation, but the patient's previously prescribing clinician must first agree that the taper is clinically reasonable and agree to conduct the taper after first discussing the risks and benefits of the taper and discontinuation with the child and parent(s). The study term will not conduct or oversee the medication taper.
- 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.
- Patients currently in foster care.
- Patients currently receiving psychotherapy.
- Patients who are receiving psychotherapy and who, together with their parents and treating clinician, agree that it is reasonable either to pause or discontinue their psychotherapy for the duration of the 24-week trial, will be permitted to do so and may then enroll in our SMART study.
- Patients with a past diagnosis of Bipolar Disorder, as determined by medical chart and medical history review by the site director and PI OR Patients who score ≥18 on the Parent General Behavior Inventory-10-Item Mania Scale (PGBI-10M) (possible range 0-30, higher scores representing an increased likelihood of diagnosis).
- Patients with a current/active psychotic diagnosis (schizophrenia, schizoaffective, schizophreniform, psychosis not otherwise specified (NOS), or depression with psychotic features), as determined by medical chart and medical history review by the site director and PI.
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Hospital Los Angeles
Los Angeles, California, 90027
About this study
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
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:
- 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
- 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
- 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
- The study will assess the stability of treatment response for ≥12 months following completion of the 24-week trial
- Conditions
- Anxiety Disorders
- Being tested
- Fluoxetine, Cognitive Behavioral Therapy (CBT)
- Medical subject headings
- Anxiety Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FluoxetineDrug
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).
Cognitive Behavioral Therapy (CBT)Behavioural
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.
| Study group | Role | What they receive |
|---|---|---|
| Medication - Fluoxetine | Active comparator | 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. Receives: Drug: Fluoxetine |
| Cognitive Behavioral Therapy (CBT) | Active comparator | 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. Receives: Behavioral: Cognitive Behavioral Therapy (CBT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Youth - SCARED (Screen for Child Anxiety Related Disorders)
Patient ratings of anxiety symptom severity. Possible range of scores is 0-82, with higher scores indicating greater severity.
Measured: Week 24
Secondary outcomes (3)
Parent - SCARED (Screen for Child Anxiety Related Disorders)
Parent ratings of anxiety symptom severity. Possible range of scores is 0-82, with higher scores indicating greater severity.
Measured: Week 24
Youth - Child Anxiety Impact Scale (CAIS)
Patient ratings of anxiety functional impairment. Possible range of scores is 0-81, with higher scores indicating greater impact.
Measured: Week 24
Parent - Child Anxiety Impact Scale (CAIS)
Parent ratings of anxiety functional impairment. Possible range of scores is 0-81, with higher scores indicating greater impact.
Measured: Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Feb 2021
- Study start10 Feb 2021
- Primary completion23 Feb 2025
- Study completionJul 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Anxiety DisordersStudies of the same condition, open and under way.
- More trials run by Children's Hospital Los AngelesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 316 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital Los Angeles
- Sponsor type
- University, hospital or other
- Collaborators
- Patient-Centered Outcomes Research Institute
- Responsible party
- Principal investigator, Bradley Peterson, Children's Hospital Los Angeles
- Investigators
- Bradley S. Peterson, MD, Principal investigator, Children's Hospital Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04760275
- Sponsor's protocol ID
- CHLA-19-00478
- Other IDs
- 16008
- Acronym
- SMART
- Status last verified
- Apr 2025
- First submitted
- 9 Feb 2021
- Last updated
- 11 Apr 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All individual participant data that are primary and secondary trial outcomes used for the Patient-Centered Outcomes Research Institute (PCORI) Final Research Report.
Publications
Peterson BS, West AE, Weisz JR, Mack WJ, Kipke MD, Findling RL, Mittman BS, Bansal R, Piantadosi S, Takata G, Koebnick C, Ashen C, Snowdy C, Poulsen M, Arora BK, Allem CM, Perez M, Marcy SN, Hudson BO, Chan SH, Weersing R. A Sequential Multiple Assignment Randomized Trial (SMART) study of medication and CBT sequencing in the treatment of pediatric anxiety disorders. BMC Psychiatry. 2021 Jun 30;21(1):323. doi: 10.1186/s12888-021-03314-y.
PubMed 34193105
Study at a glance
From the registry record, last updated by the sponsor on 11 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04760275
- Acronym / sponsor ID
- SMART / CHLA-19-00478
- Conditions
- Anxiety Disorders
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 316 participants (actual)
- Lead sponsor
- Children's Hospital Los AngelesUniversity, hospital or other
- Collaborators
- Patient-Centered Outcomes Research Institute
- Study start
- 10 Feb 2021 (actual)
- Primary completion
- 23 Feb 2025 (actual)
- Study completion
- Jul 2026 (estimated)
- First posted
- 18 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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
- 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
- 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
- The study will assess the stability of treatment response for ≥12 months following completion of the 24-week trial
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Medication - Fluoxetine | Active comparator | Drug: FluoxetineApproved 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. |
| Cognitive Behavioral Therapy (CBT) | Active comparator | Behavioral: 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. |
Who may qualify
- Ages
- 8 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- Patients ages 8-17
- 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).
- 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, computerized version (KSADS-COMP).
- 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.
- Patients and at least one parent/caregiver of all ages, who are fluent in either English or Spanish.
Key exclusion criteria (18 listed)
- Patients with a neurological disorder or unstable medical condition, as determined by medical chart and medical history review by the site director and PI.
- Females who are pregnant or sexually active but not using an effective method of birth control (potential adverse fetal effects of medication).
- 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):
- Patients with a current obsessive-compulsive disorder (OCD) diagnosis, for which this study's treatments would be inappropriate clinically and ethically, on the KSADS-COMP.
- 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) and KSADS-COMP:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FluoxetineThis 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). | Drug | Medication - Fluoxetine |
| 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. | Behavioural | Cognitive Behavioral Therapy (CBT) |
Primary outcome
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.
3 secondary outcomes
Parent - SCARED (Screen for Child Anxiety Related Disorders)
Time frame: Week 24
Youth - Child Anxiety Impact Scale (CAIS)
Time frame: Week 24
Parent - Child Anxiety Impact Scale (CAIS)
Time frame: Week 24
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Apr 2025.
- Derived from this study: PubMed 34193105Peterson BS, West AE, Weisz JR, Mack WJ, Kipke MD, Findling RL, Mittman BS, Bansal R, Piantadosi S, Takata G, Koebnick C, Ashen C, Snowdy C, Poulsen M, Arora BK, Allem CM, Perez M, Marcy SN, Hudson BO, Chan SH, Weersing R. A Sequential Multiple Assignment Randomized Trial (SMART) study of medication and CBT sequencing in the treatment of pediatric anxiety disorders. BMC Psychiatry. 2021 Jun 30;21(1):323. doi: 10.1186/s12888-021-03314-y.
- Individual participant dataSharing planned: Yes. All individual participant data that are primary and secondary trial outcomes used for the Patient-Centered Outcomes Research Institute (PCORI) Final Research Report.
Related trials for Anxiety Disorders
Not yet recruiting
Effect of Stress Ball Use During Femoral Arterial Sheath Removal After Coronary Angiography
Femoral Arterial Sheath Removal, Stress Ball
Recruiting
Unified Protocol in Penitentiary Facilities
Depression Disorders, Anxiety
Not yet recruiting
Preventive and Personalized Digital Emotion Regulation Skills Intervention to Reduce Depression and Anxiety in Youths With Adverse Childhood Experiences
Adverse Childhood Experience, Depression / Major Depressive Disorder
Recruiting
Effect of a Brief Daily Digital Meditation on Well-Being in US Young Adults (BEGIN II)
Mental Health and General Well-being
Not yet recruitingObservational study
Functional Impact of Psychological Symptoms in Patients With Superior Semicircular Canal Dehiscence Syndrome (SSCD): a National Cross-sectional Study
Superior Semicircular Canal Dehiscence
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bradley S. Peterson, MD principal investigator
Children's Hospital Los Angeles
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Fluoxetine and Cognitive Behavioral Therapy (CBT) in people with Anxiety Disorders, run by Children's Hospital Los Angeles at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 11 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Youth - SCARED (Screen for Child Anxiety Related Disorders) (time frame: Week 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04760275, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Apr 2025.