Anorexia Nervosa, Restricting TypeNCT02948452
Anxiety and Reward Interaction and Prediction of Outcomes in Anorexia Nervosa
An observational study of Anorexia Nervosa, Restricting Type and Anxiety, run by University of California, Los Angeles at 1 site in United States.
Trial summary
This study is designed to understand responsiveness to reward in adolescents with restricting-type anorexia nervosa compared with non-clinical controls, and how it is affected by potential-threat perception. Read more about this study
- Who is it for?
- Ages 12 to 19 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Anorexia Nervosa, Restricting Type, Anxiety
- What is being tested?
- fMRI
- How many people
- 66 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2015to 30 Jun 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
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 12 to 19 years
- Women only
- Healthy volunteers accepted
- Child, Adult
Study population: Investigators will enroll 96 participants between the ages of 13 and 19 (48 with anorexia nervosa and 48 non-clinical controls matched by gender.
Who may be able to join
- Clinical diagnosis of Anorexia Nervosa, Restricting Type within the previous 6 months, (except for the amenorrhea criteria)
- completed treatment in an inpatient, residential, or partial hospitalization program (2-5 times/week) consisting of psychotherapy and dietary monitoring, within the previous 3 weeks
- May be unmedicated, or be taking a serotonin reuptake inhibitor medication at a stable dose for at least 8 weeks at the time of enrollment.
- non-clinical females who score at least 1 standard deviation higher than population norms on the Depression Anxiety Stress Scale (DASS-21)
Who cannot join
- lifetime Axis I bipolar disorder, lifetime psychotic disorders, lifetime attention deficit hyperactivity disorder, or current post-traumatic stress disorder.
- current substance abuse or dependence, including nicotine
- pathological gambling, as assessed with the South Oaks Gambling Screen
- current neurological disorder
- pregnancy
- current major medical disorders that may affect cerebral metabolism such as diabetes or thyroid disorders
Show all 23Show fewer
- current risk of suicide with a plan and intent
- a Children's Depression Rating Scale Revised (CDRS-R) score >75 or major depressive disorder with psychotic features
- ferromagnetic metal implantations or devices (electronic implants or devices, infusion pumps, aneurysm clips, metal fragments or foreign bodies, metal prostheses, joints, rods or plates)
- adjusted BMI ≥ 25 (overweight)
- visual acuity worse than 20/35 for each eye as determined by Snellen close vision chart. Acuity may be met with corrective lenses.
- any Axis I disorder
- any psychiatric medication.
- - current substance abuse or dependence, including nicotine
- pathological gambling, as assessed with the South Oaks Gambling Screen
- current neurological disorder
- pregnancy
- current major medical disorders that may affect cerebral metabolism such as diabetes or thyroid disorders
- current risk of suicide with a plan and intent
- a Children's Depression Rating Scale Revised (CDRS-R) score >75 or major depressive disorder with psychotic features
- ferromagnetic metal implantations or devices (electronic implants or devices, infusion pumps, aneurysm clips, metal fragments or foreign bodies, metal prostheses, joints, rods or plates)
- adjusted BMI ≥ 25 (overweight)
- visual acuity worse than 20/35 for each eye as determined by Snellen close vision chart. Acuity may be met with corrective lenses.
Trial locations and contacts
1 site in 1 country.
About this study
This study is designed to understand responsiveness to reward in adolescents with restricting-type anorexia nervosa compared with non-clinical controls, and how it is affected by potential-threat perception.
Read the detailed description
The objective of this study is to understand the effects of anxiety on reward responsiveness in adolescents with anorexia nervosa (AN), and how this interaction predicts behavioral outcome subsequent to intensive treatment. Investigators plan to test, for the first time, how acute activation of threat related emotional circuitry reciprocally alters reward circuit activity, and to what degree this modulation predicts post treatment relapse. The severity of AN, its resistance to intervention, potential for quick return of illness, risk for long-term chronicity, and premature death, are well appreciated. Various forms of intensive treatment may succeed in at least partial weight restoration, yet early relapse is unusually high. The appearance early in life of prodromal anxiety phenotypes in individuals who subsequently develop AN is well documented and nearly universal. Anxiety proneness in concert with rigid self-discipline may therefore be predisposing substrates for sudden morbid apprehension about weight gain, and may contribute to subsequent behaviors including vigilant scrutiny of body size and shape and inflexible cognitive patterns regarding food and eating. In parallel, persons with restricting-type AN typically exhibit unease and reticence when exposed to novel, high reward environments. Most studies have found low fun-seeking, low novelty seeking, and reduced reward responsiveness in those with AN. In line with these observations, functional magnetic resonance imaging (fMRI) studies demonstrate aberrant reward sensitivity and reward circuit activation. However the interaction of anxiety and reward circuits has never been interrogated. There is substantial evidence of distinct yet overlapping neural systems mediating approach/reward and avoidance/anxiety, which are integrated in balancing and switching between behaviors related to the predominant valence state. Thus investigators posit that high degrees of reactivity of cortico-limbic circuits underlying anxiety may contribute mechanistically and functionally to diminished initial responsiveness to reward stimuli. This may translate clinically to lower motivation to engage in outpatient treatment - in effect, a lower drive to change behaviors and thought patterns necessary for maintaining gains or improving, based on expectancy of benefits of future outcome. The dynamic interaction between reward and anxiety systems in AN, and how dysregulation of connectivity within and between these systems mediates behavioral outcomes, has not previously been tested. Investigators will investigate this interaction using sequential fMRI paradigms and novel integrated functional-by-structural connectivity in individuals who have completed standard treatment on an eating disorder unit. Investigators will then investigate how this neural circuitry may predict degree of relapse during the subsequent 6 months.
- Conditions
- Anorexia Nervosa, Restricting Type, Anxiety
- Being tested
- fMRI
- Keywords
- anorexia nervosa, anxiety, reward, recurrence, magnetic resonance imaging
- Medical subject headings
- Anorexia Nervosa, Anxiety Disorders, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
fMRIOther
fMRI: reward task, anxiety provocation
| Study group | Role | What they receive |
|---|---|---|
| Anorexia | fMRI: reward task, anxiety provocation Receives: Other: fMRI | |
| Mild anxiety comparison group | fMRI: reward task, anxiety provocation Receives: Other: fMRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Blood oxygen level dependent (BOLD) percentage signal change as measured by fMRI in anxiety and reward brain regions of interest
Mean BOLD percentage signal change between anxiety and control conditions will be compared across anorexia nervosa and comparison participants during the reward task
Measured: within 3 weeks of discharge from an intensive treatment program
Secondary outcomes (2)
Body Mass Index (BMI) in kg/meter squared monthly for 6 months
Trajectory of BMI over 6 months after intensive treatment will be analyzed
Measured: 6 months
Eating disorder symptoms
Eating Disorder Examination (EDE)
Measured: beginning of study and at 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2016 (estimated)
- Study startNov 2015
- Primary completion30 Apr 2021
- Study completion30 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Anorexia Nervosa, Restricting TypeStudies of the same condition, open and under way.
- More trials run by University of California, 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
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 66 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Los Angeles
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Jamie Feusner, University of California, Los Angeles
- Investigators
- Jamie D Feusner, M.D., Principal investigator, University of California, Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02948452
- Sponsor's protocol ID
- 1R01MH105662-01A1
- Other IDs
- 1R01MH105662-01A1
- Status last verified
- May 2023
- First submitted
- 3 Oct 2016
- Last updated
- 31 May 2023
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Investigators will share deidentified subject-level data loaded to the new database for the National Institute of Mental Health Research Domain Criteria project (RDoC-db). The work involves defining data dictionaries for each data structure, cleaning and formatting data, and uploading the data to the appropriate National Institute of Mental Health server. The data so shared will contribute to the building of a large information commons for RDoC that will permit analyses of large data sets that have more power to uncover new relationships among highly multivariate and dimensional data sets.
Study at a glance
From the registry record, last updated by the sponsor on 31 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Anxiety and Reward Interaction and Prediction of Outcomes in Anorexia Nervosa
- ClinicalTrials.gov ID
- NCT02948452
- Acronym / sponsor ID
- 1R01MH105662-01A1
- Conditions
- Anorexia Nervosa, Restricting Type, Anxiety
- Keywords
- anorexia nervosa, anxiety, reward, recurrence, magnetic resonance imaging
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 66 participants (actual)
- Lead sponsor
- University of California, Los AngelesUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- Nov 2015
- Primary completion
- 30 Apr 2021 (actual)
- Study completion
- 30 Jun 2021 (actual)
- First posted
- 28 Oct 2016 (estimated)
- 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.
This study is designed to understand responsiveness to reward in adolescents with restricting-type anorexia nervosa compared with non-clinical controls, and how it is affected by potential-threat perception.
Detailed description
The objective of this study is to understand the effects of anxiety on reward responsiveness in adolescents with anorexia nervosa (AN), and how this interaction predicts behavioral outcome subsequent to intensive treatment. Investigators plan to test, for the first time, how acute activation of threat related emotional circuitry reciprocally alters reward circuit activity, and to what degree this modulation predicts post treatment relapse. The severity of AN, its resistance to intervention, potential for quick return of illness, risk for long-term chronicity, and premature death, are well appreciated. Various forms of intensive treatment may succeed in at least partial weight restoration, yet early relapse is unusually high. The appearance early in life of prodromal anxiety phenotypes in individuals who subsequently develop AN is well documented and nearly universal. Anxiety proneness in concert with rigid self-discipline may therefore be predisposing substrates for sudden morbid apprehension about weight gain, and may contribute to subsequent behaviors including vigilant scrutiny of body size and shape and inflexible cognitive patterns regarding food and eating. In parallel, persons with restricting-type AN typically exhibit unease and reticence when exposed to novel, high reward environments. Most studies have found low fun-seeking, low novelty seeking, and reduced reward responsiveness in those with AN. In line with these observations, functional magnetic resonance imaging (fMRI) studies demonstrate aberrant reward sensitivity and reward circuit activation. However the interaction of anxiety and reward circuits has never been interrogated. There is substantial evidence of distinct yet overlapping neural systems mediating approach/reward and avoidance/anxiety, which are integrated in balancing and switching between behaviors related to the predominant valence state. Thus investigators posit that high degrees of reactivity of cortico-limbic circuits underlying anxiety may contribute mechanistically and functionally to diminished initial responsiveness to reward stimuli. This may translate clinically to lower motivation to engage in outpatient treatment - in effect, a lower drive to change behaviors and thought patterns necessary for maintaining gains or improving, based on expectancy of benefits of future outcome. The dynamic interaction between reward and anxiety systems in AN, and how dysregulation of connectivity within and between these systems mediates behavioral outcomes, has not previously been tested. Investigators will investigate this interaction using sequential fMRI paradigms and novel integrated functional-by-structural connectivity in individuals who have completed standard treatment on an eating disorder unit. Investigators will then investigate how this neural circuitry may predict degree of relapse during the subsequent 6 months.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Anorexia | – | Other: fMRIfMRI: reward task, anxiety provocation |
| Mild anxiety comparison group | – | Other: fMRIfMRI: reward task, anxiety provocation |
Who may qualify
- Ages
- 12 to 19 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
- Study population
- Investigators will enroll 96 participants between the ages of 13 and 19 (48 with anorexia nervosa and 48 non-clinical controls matched by gender.
Key inclusion criteria (4 listed)
- Clinical diagnosis of Anorexia Nervosa, Restricting Type within the previous 6 months, (except for the amenorrhea criteria)
- completed treatment in an inpatient, residential, or partial hospitalization program (2-5 times/week) consisting of psychotherapy and dietary monitoring, within the previous 3 weeks
- May be unmedicated, or be taking a serotonin reuptake inhibitor medication at a stable dose for at least 8 weeks at the time of enrollment.
- non-clinical females who score at least 1 standard deviation higher than population norms on the Depression Anxiety Stress Scale (DASS-21)
Key exclusion criteria (23 listed)
- lifetime Axis I bipolar disorder, lifetime psychotic disorders, lifetime attention deficit hyperactivity disorder, or current post-traumatic stress disorder.
- current substance abuse or dependence, including nicotine
- pathological gambling, as assessed with the South Oaks Gambling Screen
- current neurological disorder
- pregnancy
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 |
|---|---|---|
| fMRIfMRI: reward task, anxiety provocation | Other | Anorexia, Mild anxiety comparison group |
Primary outcome
Blood oxygen level dependent (BOLD) percentage signal change as measured by fMRI in anxiety and reward brain regions of interest
Time frame: within 3 weeks of discharge from an intensive treatment program
Mean BOLD percentage signal change between anxiety and control conditions will be compared across anorexia nervosa and comparison participants during the reward task
2 secondary outcomes
Body Mass Index (BMI) in kg/meter squared monthly for 6 months
Time frame: 6 months
Eating disorder symptoms
Time frame: beginning of study and at 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 May 2023.
- Individual participant dataSharing planned: Yes. Investigators will share deidentified subject-level data loaded to the new database for the National Institute of Mental Health Research Domain Criteria project (RDoC-db). The work involves defining data dictionaries for each data structure, cleaning and formatting data, and uploading the data to the appropriate National Institute of Mental Health server. The data so shared will contribute to the building of a large information commons for RDoC that will permit analyses of large data sets that have more power to uncover new relationships among highly multivariate and dimensional data sets.
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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.
Jamie D Feusner, M.D. principal investigator
University of California, Los Angeles
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Anorexia Nervosa, Restricting Type and Anxiety, run by University of California, 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 4 inclusion and 23 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 31 May 2023. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Blood oxygen level dependent (BOLD) percentage signal change as measured by fMRI in anxiety and reward brain regions of interest (time frame: within 3 weeks of discharge from an intensive treatment program). 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 31 May 2023.