Binge Eating, Eating Disorders, Purging (Eating Disorders)
Conditions
Keywords
Pediatric, Adolescent, Eating Disorder, Neuroimaging, Naltrexone
Brief summary
The purpose of this open-label, pilot study is to evaluate fMRI as a biomarker of opioid antagonism in adolescents with ED. Modulation of brain activation will be examined in regions of interest by fMRI using a food-specific and general reward task in adolescents with ED in a pre/post design.
Detailed description
This is an open-label, interventional trial to evaluate reward system modulation (detected by neuroimaging) in response to opioid antagonism (i.e., naltrexone) in adolescents aged 13-21 years with an eating disorder characterized by the target behaviors of binge eating and/or purging (e.g., AN-BP, BN, BED). A pre/post design completed on the same day will be employed to quantify within-individual change while reducing potential confounding due to known neuroimaging variables (e.g., menstrual phase, treatment changes) that may occur with time elapsed between study visits. Self-report data regarding will be captured via electronic surveys using validated instruments (where possible), structured interview, study records. Reward System Modulation by fMRI. Each scan will last approximately 1 hour and involve two reward activation paradigms: passive food view (PFV) and monetary incentive delay (MID). These two reward activation paradigms provide distinct insight and will generate pilot data to support the choice of the optimal paradigm for further testing of reward system modulation in adolescents with eating disorders. PFV provides a paradigm that is relevant to the target behaviors (i.e., binge eating, purging), has been evaluated in ED patients, in response to naltrexone in adults, and is expected to activate food cue-reactivity regions (e.g., prefrontal cortex). MID is a widely used paradigm in adolescents to detect reward anticipation and receipt particularly in the striatum and is currently being used to study the developmental trajectory of reward processing in the longitudinal Adolescent Brain Cognitive Development (ABCD) trial. To the greatest extent possible, we will harmonize our fMRI parameters with those published for ABCD. Opioid Antagonism and exposure-response linkage. A single oral dose of naltrexone hydrochloride 50 mg tablet will be administered. Plasma and urine will be obtained to measure systemic exposure to naltrexone and it primary, active metabolite, 6-beta-naltrexol, using a validated UPLC-MS/MS assay.
Interventions
DRUGNaltrexone
naltrexone 50 mg PO x 1
Sponsors
National Center for Advancing Translational Sciences (NCATS)
University of Kansas Medical Center
Children's Mercy Hospital Kansas City
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
13 Years to 21 Years
Healthy volunteers
No
Inclusion criteria
* Eating disorder diagnosis per DSM-V criteria that is characterized by binge eating (defined as loss of control of eating resulting in large amount of food consumed in a short period of time) and/or purging (e.g., vomiting, excessive exercising, laxative use) * Stable medication regimen (no dose or drug changes in the past 4 weeks) * Participant and parent/legal guardian (if under 18 years) are willing and able to provide informed permission/assent/consent for the study
Exclusion criteria
* Pregnant (via UCG) * Prior hypersensitivity reaction to naltrexone (e.g., anaphylaxis) * Non-removable metal in the body * Current naltrexone use * Self-reported opioid use in the past 7 days * A language barrier (e.g., non-English speaking) for the participant that precludes communication and/or ability to complete all study-related requirements.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in % Blood Oxygenation Level Dependent Change (%BOLD) in the Nucleus Accumbens | 2 hours post-naltrexone vs baseline | Change in %BOLD following single dose naltrexone (post-pre) within individuals during passive food view task in the nucleus accumbens |
| Change in % Blood Oxygenation Level Dependent Change (%BOLD) in the Dorsal Anterior Cingulate Cortex | 2 hours post-naltrexone vs baseline | Change in %BOLD following single dose naltrexone (post-pre) within individuals during monetary incentive delay in dorsal anterior cingulate cortex |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Exposure | 2 hours post-naltrexone | Maximum plasma concentration of naltrexone at 2 hours post-single dose |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Single Pre/Post Design Pre-naltrexone fMRI
Naltrexone: naltrexone 50 mg PO x 1
Post-naltrexone fMRI | 13 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Single Pre/Post Design |
|---|---|
| Age, Categorical <=18 years | 9 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants |
| Age, Continuous | 17 years STANDARD_DEVIATION 2.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 8 Participants |
| Region of Enrollment United States | 13 participants |
| Sex/Gender, Customized Gender identity Female | 12 Participants |
| Sex/Gender, Customized Gender identity Male | 0 Participants |
| Sex/Gender, Customized Gender identity Other (prefer to self-describe) | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 13 |
| other Total, other adverse events | 1 / 13 |
| serious Total, serious adverse events | 0 / 13 |
Outcome results
Primary
Change in % Blood Oxygenation Level Dependent Change (%BOLD) in the Dorsal Anterior Cingulate Cortex
Change in %BOLD following single dose naltrexone (post-pre) within individuals during monetary incentive delay in dorsal anterior cingulate cortex
Time frame: 2 hours post-naltrexone vs baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Single Pre/Post Design | Change in % Blood Oxygenation Level Dependent Change (%BOLD) in the Dorsal Anterior Cingulate Cortex | 0.06 %BOLD signal change | Standard Deviation 0.03 |
Primary
Change in % Blood Oxygenation Level Dependent Change (%BOLD) in the Nucleus Accumbens
Change in %BOLD following single dose naltrexone (post-pre) within individuals during passive food view task in the nucleus accumbens
Time frame: 2 hours post-naltrexone vs baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Single Pre/Post Design | Change in % Blood Oxygenation Level Dependent Change (%BOLD) in the Nucleus Accumbens | -0.08 %BOLD signal change | Standard Deviation 0.03 |
Secondary
Exposure
Maximum plasma concentration of naltrexone at 2 hours post-single dose
Time frame: 2 hours post-naltrexone
Population: plasma concentration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Single Pre/Post Design | Exposure | 44.1 nanomolar | Standard Deviation 22.7 |