AnxietyNCT03643848
Sleep and Emotional Memory in Peripubertal Anxiety
A study testing Sleep with Sound Cues in people with Anxiety, run by Florida International University at 2 sites in United States.
Trial summary
The current study aims to deepen understanding of the symptom dimension of negative overgeneralization in anxiety. Specifically, the study examines the malleability of memory processes that are known to occur during sleep that may underlie negative overgeneralization. Read more about this study
- Who is it for?
- Ages 10 to 13 yearsHealthy volunteers can take part
- Conditions the study is for
- Anxiety
- What is being tested?
- Sleep with Sound Cues
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 58 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 Jun 2018to 1 Mar 2024
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 10 to 13 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- 10-13 years old
- Able to understand and communicate in English and have a parent who is able to understand and communicate in English or Spanish
- included across any range of symptoms of anxiety, and may meet full diagnostic criteria for Social Phobia, Generalized Anxiety and Separation Anxiety.
- be right-handed.
Who cannot join
- For youth to be excluded from participation, they must:
- meet diagnostic criteria for Organic Mental Disorders, Psychotic Disorders, Pervasive Developmental Disorders (including autism spectrum disorders), Obsessive Compulsive Disorder, Attention-Deficit Hyperactivity Disorder, Conduct Disorder, Oppositional Defiant Disorder, Posttraumatic Stress Disorder, Bipolar Disorder, Tic disorder, Impulse Control Disorder, or Intellectual Disability. However, to improve generalizability, if Attention-Deficit Hyperactivity Disorder, Oppositional Defiant Disorder, Obsessive Compulsive Disorder, Mood Disorders (including past or present episodes of Major Depressive Disorder and/or dysthymia) or Posttraumatic stress Disorder co-occurs with an anxiety disorder (see Inclusion Criteria above) participants may be included.
- Children complete the Wechsler Abbreviated Scale of Intelligence, Second Edition (WASI-II). Scores below 80 (i.e., two standard deviations below normed mean) are considered exclusionary for this study.
- show high likelihood and/or serious intent of hurting themselves or others.
- have not been living with a primary caregiver for at least 6 months who is legally able to give consent for the child's participation.
- be a victim of previously undisclosed abuse requiring investigation or ongoing supervision by the Department of Children and Families;
Show all 18Show fewer
- have a serious vision problem that is not corrected with prescription lenses, or have prescription glasses outside of the range of -5.00 to +3.00 (contact lenses are ok).
- have a physical disability that interferes with their ability to lie in scanner and/or click a mouse button rapidly;
- have a serious hearing problem;
- have a history of neurological or other major medical conditions affecting brain function.
- current or past history of sleep disorder, as assessed during the screening; exclusionary sleep disorders will include sleep apnea, and circadian rhythm disturbances (i.e., advanced or delayed sleep-phase)
- self-reported average sleep duration < 6 hours or > 11 hours across weekday and weekend nights, or normal bedtime later than 1:00 am; .
- Are not suitable to undergo MRI scanning due to claustrophobia, certain implanted devices/metal (e.g., cardiac pacemaker, neurostimulator, some artificial joints, metal pins, surgical/aneurysm clips, heart valves, cochlear implants, retinal implants, shrapnel in eye, non-removable body piercing or other non-MRI compatible metal/device.
- Are pregnant.
- Some Color Tattoos.
- Color Contacts.
- Currently sick or recovering from illness.
- Currently taking non-stimulant psychotropic medications. However, participants who have been off non- stimulant medication for at least 2 weeks (the typical washout period) may be included. Participants currently taking stimulant medications may be included, as long as medication was not taken within 24 hours of scans (at the discretion of the parent/legal guardian and prescribing physician).
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Center for Children and Families, Florida International University
Miami, Florida, 33199
Nicklaus Children's Hospital
Miami, Florida, 33199
About this study
Official title: Sleep-dependent Negative Overgeneralization in Peri-pubertal Anxiety
The current study aims to deepen understanding of the symptom dimension of negative overgeneralization in anxiety. Specifically, the study examines the malleability of memory processes that are known to occur during sleep that may underlie negative overgeneralization.
Read the detailed description
Up to 50% of peripubertal youth with anxiety have unmet clinical needs, leaving these youth at high risk for suicide, depression and substance abuse across adolescence. In accord with the NIMH strategic plan, the proposal aims to deepen mechanistic understanding of anxiety during the sensitive period of peripuberty to inform novel treatments and reduce health risks. The focus is on negative overgeneralization, which is a core dimension of anxiety that is poorly understood, and refers to the tendency to generalize aversive responses from one context (house fire) to other contexts (camp-fire) that share features. Amygdala activity, induced by heightened emotional arousal, enhances plasticity in associative learning mechanisms, facilitating the binding of contextual features in memory that are only loosely related. The proposal posits that sleep plays a critical role in negative overgeneralization. Specifically, the proposal draws from basic neuroscience to posit a model by which heightened amygdala reactivity during wakefulness, induced by increased emotional arousal, facilitates replay of negative memories during sleep. This facilitated replay leads to the stabilization and integration (consolidation) of negative memories into long-term memory networks via slow wave oscillatory events during NREM sleep. The proposal further posits that facilitated replay of negative memories during sleep promotes generalization by influencing underlying neurocomputational mechanisms (i.e., pattern completion - a computational process that makes neural representations similar). Finally, the proposal posits that sleep-dependent consolidation is malleable, such that Targeted Memory Reactivation (TMR) of positive memories during sleep can competitively displace consolidation of negative memories. This model is tested using a novel multi-method approach combining neuroimaging, polysomnography, and a memory task that captures behavioral generalization and its underlying neural mechanisms (i.e. pattern completion).
Aims 1 and 2 do not involve a clinical trial. Aim 1 examines 200 peripubertal youth (ages 10-13 years) across a full continuum of anxious symptoms in a randomized sleep (n=140) versus wake (n=60) design to demonstrate sleep-dependent effects on behavioral and neural mechanisms of negative overgeneralization. Aim 2 focuses on the 140 youth in the sleep condition to evaluate amygdala reactivity at encoding and sleep neurophysiology during post-encoding sleep as mediators between anxiety and negative overgeneralization.
Aim 3 is the clinical trial to which this registration refers. In Aim 3, the same design as the sleep condition (above) is used, but a new sample of youth with elevated anxiety (n=60) is recruited to enroll in a randomized trial in which neutral memories are cued during sleep (TMR, n=30), or sham cues are presented during sleep (n=30), to examine malleability of sleep-dependent mechanisms of negative overgeneralization. This project will set the stage for the long-term goal of developing novel interventions that manipulate sleep (e.g. via TMR) not only to improve existing symptoms, but also to positively shape neurodevelopment and reduce risk in the sensitive period of peripuberty.
- Conditions
- Anxiety
- Being tested
- Sleep with Sound Cues, Sleep with Sham Cues
- Medical subject headings
- Anxiety Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sleep with Sound CuesBehavioural
Experimental manipulation to observe effects on memory for learned material.
Sleep with Sham CuesBehavioural
Sham manipulation
| Study group | Role | What they receive |
|---|---|---|
| Sleep with Sound Cues | Experimental | Sounds played at time of memory encoding will be replayed during sleep to cue memory processing. Receives: Behavioral: Sleep with Sound Cues |
| Sleep with Sham Cues | Sham comparator | Sounds that were not played at time of memory encoding will be played during sleep as a sham comparison Receives: Behavioral: Sleep with Sham Cues |
What is being measured
The primary outcome is the main question the study is designed to answer.
Scores on the Lure Generalization Index (a Behavioral Measure of Generalization)
Emotional Mnemonic Similarity Task. Participants view pictures depicting negative or neutral objects/scenes. After a delay period (1 week) they are presented with a second set of pictures that are the same (targets), slightly different (lures), or completely different (foils) from the first series of pictures. They are told to indicate by button press if images they are currently viewing are "old" or "new". Responding to the lures as old ("false alarms") provides a signature of generalization for each participant. To correct for response biases (i.e., a tendency to label items as "old") a Lure Generalization Index (LGI) is calculated which reflects corrected memory generalization by subtracting false alarm rates to foils from false alarm rates to lures. Larger LGI values indicate greater generalization (i.e., greater tendency to misidentify similar items as previously seen, accounting for overall biases to identify any items as previously seen). Minimum value -1 and maximum value =1
Measured: Delayed recall, 1 week
Secondary outcomes (1)
Scores on the Lure Generalization Index (a Behavioral Measure of Generalization)
Emotional Mnemonic Similarity Task. Participants view pictures depicting negative or neutral objects/scenes. After a delay period (12 hours) they are presented with a second set of pictures that are the same (targets), slightly different (lures), or completely different (foils) from the first series of pictures. They are told to indicate by button press if images they are currently viewing are "old" or "new". Responding to the lures as old ("false alarms") provides a signature of generalization for each participant. To correct for response biases (i.e., a tendency to label items as "old") a Lure Generalization Index (LGI) is calculated which reflects corrected memory generalization by subtracting false alarm rates to foils from false alarm rates to lures. Larger LGI values indicate greater generalization (i.e., greater tendency to misidentify similar items as previously seen, accounting for overall biases to identify any items as previously seen). Minimum value -1 and maximum value =1
Measured: Recall, 12 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Aug 2018
- Study start1 Jun 2018
- Primary completion1 Mar 2024
- Study completion1 Mar 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for AnxietyStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Per NIMH policy at the time of funding, the current trial is considered a clinical trial due to prospective, randomized assignment to an "intervention" to observe effects on behavioral or health related outcomes. The "intervention" for Aim 3 (n=60) includes randomized assignment to sham sounds (sounds unrelated to the memory task) or target sounds (sounds that were played during the time of the memory task) that are played during sleep to cue memory processing.
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 58 participants (actual)
Sponsor and investigators
- Lead sponsor
- Florida International University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Dana McMakin, PhD, Principal investigator, Florida International University and Nicklaus Children's HospitalAaron Mattfeld, PhD, Principal investigator, Florida International University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03643848
- Sponsor's protocol ID
- 1R01MH116005-01
- Status last verified
- Aug 2025
- First submitted
- 19 Jul 2018
- Last updated
- 11 Sep 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: yes, data are shared via NIH NDA and include behavioral, imaging, polysomnography and clinical data.
Study at a glance
From the registry record, last updated by the sponsor on 11 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sleep-dependent Negative Overgeneralization in Peri-pubertal Anxiety
- ClinicalTrials.gov ID
- NCT03643848
- Acronym / sponsor ID
- 1R01MH116005-01
- Conditions
- Anxiety
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 58 participants (actual)
- Lead sponsor
- Florida International UniversityUniversity, hospital or other
- Study start
- 1 Jun 2018 (actual)
- Primary completion
- 1 Mar 2024 (actual)
- Study completion
- 1 Mar 2024 (actual)
- First posted
- 23 Aug 2018 (actual)
- Results
- Posted 11 Sep 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The current study aims to deepen understanding of the symptom dimension of negative overgeneralization in anxiety. Specifically, the study examines the malleability of memory processes that are known to occur during sleep that may underlie negative overgeneralization.
Detailed description
Up to 50% of peripubertal youth with anxiety have unmet clinical needs, leaving these youth at high risk for suicide, depression and substance abuse across adolescence. In accord with the NIMH strategic plan, the proposal aims to deepen mechanistic understanding of anxiety during the sensitive period of peripuberty to inform novel treatments and reduce health risks. The focus is on negative overgeneralization, which is a core dimension of anxiety that is poorly understood, and refers to the tendency to generalize aversive responses from one context (house fire) to other contexts (camp-fire) that share features. Amygdala activity, induced by heightened emotional arousal, enhances plasticity in associative learning mechanisms, facilitating the binding of contextual features in memory that are only loosely related. The proposal posits that sleep plays a critical role in negative overgeneralization. Specifically, the proposal draws from basic neuroscience to posit a model by which heightened amygdala reactivity during wakefulness, induced by increased emotional arousal, facilitates replay of negative memories during sleep. This facilitated replay leads to the stabilization and integration (consolidation) of negative memories into long-term memory networks via slow wave oscillatory events during NREM sleep. The proposal further posits that facilitated replay of negative memories during sleep promotes generalization by influencing underlying neurocomputational mechanisms (i.e., pattern completion - a computational process that makes neural representations similar). Finally, the proposal posits that sleep-dependent consolidation is malleable, such that Targeted Memory Reactivation (TMR) of positive memories during sleep can competitively displace consolidation of negative memories. This model is tested using a novel multi-method approach combining neuroimaging, polysomnography, and a memory task that captures behavioral generalization and its underlying neural mechanisms (i.e. pattern completion).
Aims 1 and 2 do not involve a clinical trial. Aim 1 examines 200 peripubertal youth (ages 10-13 years) across a full continuum of anxious symptoms in a randomized sleep (n=140) versus wake (n=60) design to demonstrate sleep-dependent effects on behavioral and neural mechanisms of negative overgeneralization. Aim 2 focuses on the 140 youth in the sleep condition to evaluate amygdala reactivity at encoding and sleep neurophysiology during post-encoding sleep as mediators between anxiety and negative overgeneralization.
Aim 3 is the clinical trial to which this registration refers. In Aim 3, the same design as the sleep condition (above) is used, but a new sample of youth with elevated anxiety (n=60) is recruited to enroll in a randomized trial in which neutral memories are cued during sleep (TMR, n=30), or sham cues are presented during sleep (n=30), to examine malleability of sleep-dependent mechanisms of negative overgeneralization. This project will set the stage for the long-term goal of developing novel interventions that manipulate sleep (e.g. via TMR) not only to improve existing symptoms, but also to positively shape neurodevelopment and reduce risk in the sensitive period of peripuberty.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- Per NIMH policy at the time of funding, the current trial is considered a clinical trial due to prospective, randomized assignment to an "intervention" to observe effects on behavioral or health related outcomes. The "intervention" for Aim 3 (n=60) includes randomized assignment to sham sounds (sounds unrelated to the memory task) or target sounds (sounds that were played during the time of the memory task) that are played during sleep to cue memory processing.
| Arm | Type | Receives |
|---|---|---|
| Sleep with Sound Cues | Experimental | Behavioral: Sleep with Sound CuesSounds played at time of memory encoding will be replayed during sleep to cue memory processing. |
| Sleep with Sham Cues | Sham comparator | Behavioral: Sleep with Sham CuesSounds that were not played at time of memory encoding will be played during sleep as a sham comparison |
Who may qualify
- Ages
- 10 to 13 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- 10-13 years old
- Able to understand and communicate in English and have a parent who is able to understand and communicate in English or Spanish
- included across any range of symptoms of anxiety, and may meet full diagnostic criteria for Social Phobia, Generalized Anxiety and Separation Anxiety.
- be right-handed.
Key exclusion criteria (18 listed)
- For youth to be excluded from participation, they must:
- meet diagnostic criteria for Organic Mental Disorders, Psychotic Disorders, Pervasive Developmental Disorders (including autism spectrum disorders), Obsessive Compulsive Disorder, Attention-Deficit Hyperactivity Disorder, Conduct Disorder, Oppositional Defiant Disorder, Posttraumatic Stress Disorder, Bipolar Disorder, Tic disorder, Impulse Control Disorder, or Intellectual Disability. However, to improve generalizability, if Attention-Deficit Hyperactivity Disorder, Oppositional Defiant Disorder, Obsessive Compulsive Disorder, Mood Disorders (including past or present episodes of Major Depressive Disorder and/or dysthymia) or Posttraumatic stress Disorder co-occurs with an anxiety disorder (see Inclusion Criteria above) participants may be included.
- Children complete the Wechsler Abbreviated Scale of Intelligence, Second Edition (WASI-II). Scores below 80 (i.e., two standard deviations below normed mean) are considered exclusionary for this study.
- show high likelihood and/or serious intent of hurting themselves or others.
- have not been living with a primary caregiver for at least 6 months who is legally able to give consent for the child's participation.
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 |
|---|---|---|
| Sleep with Sound CuesExperimental manipulation to observe effects on memory for learned material. | Behavioural | Sleep with Sound Cues |
| Sleep with Sham CuesSham manipulation | Behavioural | Sleep with Sham Cues |
Primary outcome
Scores on the Lure Generalization Index (a Behavioral Measure of Generalization)
Time frame: Delayed recall, 1 week
Emotional Mnemonic Similarity Task. Participants view pictures depicting negative or neutral objects/scenes. After a delay period (1 week) they are presented with a second set of pictures that are the same (targets), slightly different (lures), or completely different (foils) from the first series of pictures. They are told to indicate by button press if images they are currently viewing are "old" or "new". Responding to the lures as old ("false alarms") provides a signature of generalization for each participant. To correct for response biases (i.e., a tendency to label items as "old") a Lure Generalization Index (LGI) is calculated which reflects corrected memory generalization by subtracting false alarm rates to foils from false alarm rates to lures. Larger LGI values indicate greater generalization (i.e., greater tendency to misidentify similar items as previously seen, accounting for overall biases to identify any items as previously seen). Minimum value -1 and maximum value =1
1 secondary outcome
Scores on the Lure Generalization Index (a Behavioral Measure of Generalization)
Time frame: Recall, 12 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Sep 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. yes, data are shared via NIH NDA and include behavioral, imaging, polysomnography and clinical data.
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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.
Dana McMakin, PhD principal investigator
Florida International University and Nicklaus Children's Hospital
Aaron Mattfeld, PhD principal investigator
Florida International University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Sleep with Sound Cues in people with Anxiety, run by Florida International University at 2 sites 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 4 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: finished, as of the sponsor's last update on 11 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Sep 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Scores on the Lure Generalization Index (a Behavioral Measure of Generalization) (time frame: Delayed recall, 1 week). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 Sep 2025.