Anorexia NervosaACANNCT05531604
Appetitive Conditioning in Anorexia Nervosa
An observational study of Anorexia Nervosa, run by Centre for Addiction and Mental Health at 1 site in Canada.
Trial summary
Anorexia nervosa (AN) is characterized by a reduced drive to pursue rewarding experiences and stimuli. Food consumption - which is almost universally experienced as pleasurable - is not described as rewarding by those with AN. This is thought to be underpinned by abnormalities around reward learning. Read more about this study
- Who is it for?
- Ages 12 to 22 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Anorexia Nervosa
- What is being tested?
- appetitive conditioning
- Type of treatment
- Lifestyle or therapy programme
- How many people
- 90 participants
- Where
- 1 siteCanada
- Study dates
- 30 Sep 2022to 30 Jun 2026
- Phase
- Observational
- 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 12 to 22 years
- Women only
- Healthy volunteers accepted
- Child, Adult
Study population: Investigators will enroll 90 female participants between the ages of 12 and 22 (30 with current anorexia nervosa - restricting type, 30 with a history of anorexia nervosa - restricting type, and 30 non-clinical healthy controls).
Who may be able to join
- AN-Restricting (AN-R) Group
- Females from any racial or ethnic background
- Ages between 12 and 22 years
- Meet DSM-5 criteria for AN - restricting subtype
- Medically stable designated by their physician in the past month (having any of the following measurements taken by a physician or nurse within the past month preceding the telephone screen: (i) orthostasis: drop in systolic blood pressure > 20 mm Hg or diastolic blood pressure > 10 mm Hg, or an increase in heart rate (HR) > 20 bpm upon standing for 3 minutes after lying down; (ii) resting HR <45; or (iii) resting blood pressure of <80 mm Hg systolic or <50 mm Hg diastolic 99. Prospective participants who do not meet the medical instability criteria and otherwise pass the telephone screen, will be invited to proceed to the consent process. If they have not had these measurements done in the month prior, we will encourage them to visit their doctor or nurse to have these done and then to recontact us with the results ):
- BP and pulse measured at the day of the scan by the investigators
Show all 19Show fewer
- Heart rate ≥ 45 at rest
- Resting blood pressure of ≥80 mm Hg systolic and ≥50 mm Hg diastolic
- Lying and standing (after 3 min.) BP drop of ≤20 systolic and ≤10 diastolic and increase in HR ≤20 bpm
- Not taking psychiatric medications or taking serotonin-reuptake inhibitor or serotonin-norepinephrine reuptake inhibitor medications at stable doses
- History of AN-Restricting Group:
- Females from any racial or ethnic background
- Ages between 12 and 22 years
- EDE-Q ≤ 2 (puts them within 1 standard deviation [SD] of community norms and lower than 1 SD from clinical norms for female AN-R)
- History of AN - meeting full criteria, diagnosed by a licensed clinician
- Not taking psychiatric medications or taking serotonin-reuptake inhibitor or serotonin-norepinephrine reuptake inhibitor medications at stable doses
- Healthy controls:
- Healthy females from any racial or ethnic background
- Ages 12-22 years
Who cannot join
- AN-R and History of AN-R groups:
- Antipsychotic medications
- Change in dose of psychotropic medication over the previous 4 weeks
- Current psychotic disorder
- Healthy controls:
- Any current Axis I disorder
Show all 14Show fewer
- Eating Disorder Examination Questionnaire score greater than established community norms (>2)
- Met criteria for AN (in the past or present)
- All:
- Neurological disorder
- Infants or children of their own
- Pregnancy
- Current risk of suicide with a plan and intent
- Ferromagnetic metal implantations or devices (electronic implants or devices, infusion pumps, aneurysm clips, metal fragments or foreign bodies, metal prostheses, joints, rods or plates)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Appetitive Conditioning in Anorexia Nervosa: Neural, Physiological, and Behavioral Mechanisms
Anorexia nervosa (AN) is characterized by a reduced drive to pursue rewarding experiences and stimuli. Food consumption - which is almost universally experienced as pleasurable - is not described as rewarding by those with AN. This is thought to be underpinned by abnormalities around reward learning. However, the most fundamental question relating to reward in AN - whether those with AN may learn positive associations - remains unaddressed.
In this study, the investigators will identify the patterns of how those with AN acquire positive associations, how they diminish, and their relationships to physiology (heart rate and pupil responses) and brain activation. In assessing the robustness of this learning, the investigators will investigate the extent to which this association is reactivated after 24 hours, and the extent to which a memory prompt will help reinstate this previously learned positive association.
This project will allow for important advances in our understanding of the neurobiology of AN. The investigators will first identify if, and how, those with AN come to learn positive associations to cues, and secondly, the extent to which learned positive associations remain over time. Moreover, the investigators will use machine learning to ascertain whether reward learning can be predicted by physiological and neural biomarkers.
Read the detailed description
Individuals with anorexia nervosa (AN) suffer from anxiety, reduced pleasure from normally rewarding situations (anhedonia), and disturbed body image. However, restriction of calories from their morbid fear of weight gain, resulting in starvation, typically brings them to attention and has been the primary focus of most treatments and many research studies. Yet, treatments have largely been inadequate, with remission rates less than 25%. Anhedonia and disturbances in reward may be important targets of new treatment approaches. Those with AN report little pleasure in food consumption, social domains, and pursuit of novelty and fun. Neuroimaging studies demonstrate disturbances in reward circuits in response to food- and body-related stimuli and monetary rewards, but results are inconsistent. This may be due to confounding effects of anxiety triggered by symptom-related stimuli. Further, a fundamental process of the overall reward response that has not been studied in AN is reward learning - how one's brain learns to associate stimuli with the experience of reward ("appetitive Pavlovian conditioning"). To investigate this, the investigators will enroll 30 underweight individuals with AN, 30 with weight-restored AN, and 30 healthy controls ages 12-22 to perform a reward conditioning paradigm. The investigators will use infant laughter, a social reward with robust effects that is unlikely to be confounded by other co-occurring symptoms. To understand associated neural activity and physiological responses, the investigators will perform conditioning and examine reinstatement 24-hours later, while obtaining functional magnetic resonance imaging, heart rate deceleration, and pupil dilation data, in addition to subjective degrees of positive experience. Data from underweight and weight-restored AN will further allow us to probe starvation state-related effects. Results will advance our understanding of how reward stimuli are learned and the associated aberrant neural or physiological markers. This will yield a comprehensive mechanistic understanding of hedonic functioning in AN to rationally inform future novel treatment development.
- Conditions
- Anorexia Nervosa
- Being tested
- appetitive conditioning
- Keywords
- appetitive conditioning, pavlovian conditioning, reward learning, reinforcement learning, associative learning, extinction
- Medical subject headings
- Anorexia Nervosa
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
appetitive conditioningBehavioural
The investigators will examine acquisition and extinction of learned associations to positively-valenced, socially rewarding yet symptom-neutral infant laughter sounds in an appetitive conditioning paradigm. The investigators will also examine spontaneous recovery of this association 24 hours later when re-presented with these cues, and the reinstatement of this association when re-exposed to infant laughter.
| Study group | Role | What they receive |
|---|---|---|
| AN-Restricting (AN-R) | Meet Diagnostic and Statistical Manual (DSM-5) criteria for anorexia nervosa, restricting subtype Receives: Behavioral: appetitive conditioning | |
| Weight Restored AN-Restricting (WRAN-R) | * History of anorexia nervosa, restricting type - previously meeting full DSM-5 criteria.
* Eating Disorder Examination Questionnaire (EDE-Q) ≤ 2 (within 1 standard deviation [SD] of community norms and lower than 1 standard deviation from clinical norms for female anorexia nervosa, restricting type populations) Receives: Behavioral: appetitive conditioning | |
| Healthy controls | Healthy females from any racial or ethnic background, not meeting DSM-5 criteria for any psychiatric disorder. Receives: Behavioral: appetitive conditioning |
What is being measured
The primary outcome is the main question the study is designed to answer.
Positive valence
A 10-point Likert scale will assess self-reported pleasantness and arousal for each conditioned stimulus, and unconditioned stimulus expectancy
Measured: Day 1
Positive valence
A 10-point Likert scale will assess self-reported pleasantness and arousal for each conditioned stimulus, and unconditioned stimulus expectancy
Measured: Day 2
Pupillary dilation
Measured with an eye-tracking camera
Measured: Day 1
Pupillary dilation
Measured with an eye-tracking camera
Measured: Day 2
Heart rate deceleration
Measured with an electrocardiogram
Measured: Day 1
Heart rate deceleration
Measured with an electrocardiogram
Measured: Day 2
Brain activation
Neural activation in reward circuits measured with functional magnetic resonance imaging
Measured: Day 1
Brain activation
Neural activation in reward circuits measured with functional magnetic resonance imaging
Measured: Day 2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Sep 2022
- Study start30 Sep 2022
- Primary completion25 Dec 2025
- Study completion30 Jun 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 Anorexia NervosaStudies 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
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centre for Addiction and Mental Health
- Sponsor type
- University, hospital or other
- Collaborators
- University of Southern California, University of Toronto, California Institute of Technology, Klarman Family Foundation
- Responsible party
- Sponsor
- Investigators
- Jamie D Feusner, M.D., Principal investigator, Centre for Addiction and Mental HealthStuart Murray, Ph.D., Principal investigator, University of Southern California
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05531604
- Sponsor's protocol ID
- 20202201
- Acronym
- ACAN
- Status last verified
- Nov 2025
- First submitted
- 30 Aug 2022
- Last updated
- 27 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Murray SB, Zbozinek TD, Craske M, Tadayonnejad R, Strober M, Bari AA, O'Doherty JP, Feusner JD. Neural, physiological, and psychological markers of appetitive conditioning in anorexia nervosa: a study protocol. J Eat Disord. 2022 May 10;10(1):68. doi: 10.1186/s40337-022-00546-5.
PubMed 35538507
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Appetitive Conditioning in Anorexia Nervosa: Neural, Physiological, and Behavioral Mechanisms
- ClinicalTrials.gov ID
- NCT05531604
- Acronym / sponsor ID
- ACAN / 20202201
- Conditions
- Anorexia Nervosa
- Keywords
- appetitive conditioning, pavlovian conditioning, reward learning, reinforcement learning, associative learning, extinction
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- Centre for Addiction and Mental HealthUniversity, hospital or other
- Collaborators
- University of Southern California, University of Toronto, California Institute of Technology, Klarman Family Foundation
- Study start
- 30 Sep 2022 (actual)
- Primary completion
- 25 Dec 2025 (actual)
- Study completion
- 30 Jun 2026 (estimated)
- First posted
- 8 Sep 2022 (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.
Anorexia nervosa (AN) is characterized by a reduced drive to pursue rewarding experiences and stimuli. Food consumption - which is almost universally experienced as pleasurable - is not described as rewarding by those with AN. This is thought to be underpinned by abnormalities around reward learning. However, the most fundamental question relating to reward in AN - whether those with AN may learn positive associations - remains unaddressed.
In this study, the investigators will identify the patterns of how those with AN acquire positive associations, how they diminish, and their relationships to physiology (heart rate and pupil responses) and brain activation. In assessing the robustness of this learning, the investigators will investigate the extent to which this association is reactivated after 24 hours, and the extent to which a memory prompt will help reinstate this previously learned positive association.
This project will allow for important advances in our understanding of the neurobiology of AN. The investigators will first identify if, and how, those with AN come to learn positive associations to cues, and secondly, the extent to which learned positive associations remain over time. Moreover, the investigators will use machine learning to ascertain whether reward learning can be predicted by physiological and neural biomarkers.
Detailed description
Individuals with anorexia nervosa (AN) suffer from anxiety, reduced pleasure from normally rewarding situations (anhedonia), and disturbed body image. However, restriction of calories from their morbid fear of weight gain, resulting in starvation, typically brings them to attention and has been the primary focus of most treatments and many research studies. Yet, treatments have largely been inadequate, with remission rates less than 25%. Anhedonia and disturbances in reward may be important targets of new treatment approaches. Those with AN report little pleasure in food consumption, social domains, and pursuit of novelty and fun. Neuroimaging studies demonstrate disturbances in reward circuits in response to food- and body-related stimuli and monetary rewards, but results are inconsistent. This may be due to confounding effects of anxiety triggered by symptom-related stimuli. Further, a fundamental process of the overall reward response that has not been studied in AN is reward learning - how one's brain learns to associate stimuli with the experience of reward ("appetitive Pavlovian conditioning"). To investigate this, the investigators will enroll 30 underweight individuals with AN, 30 with weight-restored AN, and 30 healthy controls ages 12-22 to perform a reward conditioning paradigm. The investigators will use infant laughter, a social reward with robust effects that is unlikely to be confounded by other co-occurring symptoms. To understand associated neural activity and physiological responses, the investigators will perform conditioning and examine reinstatement 24-hours later, while obtaining functional magnetic resonance imaging, heart rate deceleration, and pupil dilation data, in addition to subjective degrees of positive experience. Data from underweight and weight-restored AN will further allow us to probe starvation state-related effects. Results will advance our understanding of how reward stimuli are learned and the associated aberrant neural or physiological markers. This will yield a comprehensive mechanistic understanding of hedonic functioning in AN to rationally inform future novel treatment development.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| AN-Restricting (AN-R) | – | Behavioral: appetitive conditioningMeet Diagnostic and Statistical Manual (DSM-5) criteria for anorexia nervosa, restricting subtype |
| Weight Restored AN-Restricting (WRAN-R) | – | Behavioral: appetitive conditioning* History of anorexia nervosa, restricting type - previously meeting full DSM-5 criteria. * Eating Disorder Examination Questionnaire (EDE-Q) ≤ 2 (within 1 standard deviation [SD] of community norms and lower than 1 standard deviation from clinical norms for female anorexia nervosa, restricting type populations) |
| Healthy controls | – | Behavioral: appetitive conditioningHealthy females from any racial or ethnic background, not meeting DSM-5 criteria for any psychiatric disorder. |
Who may qualify
- Ages
- 12 to 22 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
- Study population
- Investigators will enroll 90 female participants between the ages of 12 and 22 (30 with current anorexia nervosa - restricting type, 30 with a history of anorexia nervosa - restricting type, and 30 non-clinical healthy controls).
Key inclusion criteria (19 listed)
- AN-Restricting (AN-R) Group
- History of AN-Restricting Group:
- Healthy controls:
- Healthy females from any racial or ethnic background
- Ages 12-22 years
Key exclusion criteria (14 listed)
- AN-R and History of AN-R groups:
- Any current Axis I disorder
- Eating Disorder Examination Questionnaire score greater than established community norms (>2)
- Met criteria for AN (in the past or present)
- Neurological disorder
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 |
|---|---|---|
| appetitive conditioningThe investigators will examine acquisition and extinction of learned associations to positively-valenced, socially rewarding yet symptom-neutral infant laughter sounds in an appetitive conditioning paradigm. The investigators will also examine spontaneous recovery of this association 24 hours later when re-presented with these cues, and the reinstatement of this association when re-exposed to infant laughter. | Behavioural | AN-Restricting (AN-R), Healthy controls, Weight Restored AN-Restricting (WRAN-R) |
Primary outcome
Positive valence
Time frame: Day 1
A 10-point Likert scale will assess self-reported pleasantness and arousal for each conditioned stimulus, and unconditioned stimulus expectancy
Positive valence
Time frame: Day 2
A 10-point Likert scale will assess self-reported pleasantness and arousal for each conditioned stimulus, and unconditioned stimulus expectancy
Pupillary dilation
Time frame: Day 1
Measured with an eye-tracking camera
Pupillary dilation
Time frame: Day 2
Measured with an eye-tracking camera
Heart rate deceleration
Time frame: Day 1
Measured with an electrocardiogram
Heart rate deceleration
Time frame: Day 2
Measured with an electrocardiogram
Brain activation
Time frame: Day 1
Neural activation in reward circuits measured with functional magnetic resonance imaging
Brain activation
Time frame: Day 2
Neural activation in reward circuits measured with functional magnetic resonance imaging
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 27 Mar 2026.
- Background: PubMed 35538507Murray SB, Zbozinek TD, Craske M, Tadayonnejad R, Strober M, Bari AA, O'Doherty JP, Feusner JD. Neural, physiological, and psychological markers of appetitive conditioning in anorexia nervosa: a study protocol. J Eat Disord. 2022 May 10;10(1):68. doi: 10.1186/s40337-022-00546-5.
- Published manuscript of the study protocolLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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
Centre for Addiction and Mental Health
Stuart Murray, Ph.D. principal investigator
University of Southern California
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, run by Centre for Addiction and Mental Health at 1 site in Canada.
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 19 inclusion and 14 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 27 Mar 2026. 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 Canada. 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?
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?
Positive valence (time frame: Day 1). The study lists 8 primary outcomes in all. 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 NCT05531604, 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 27 Mar 2026.