Oral Naltrexone In Pediatric Eating Disorders

Study Overview
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Brief Summary
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The objective of this study is to evaluate the effectiveness of oral naltrexone tablets in pediatric and adolescent eating disorders, in particular anorexia nervosa and bulimia nervosa, as compared to placebo. Study participants will be patients in a partial hospitalization program or intensive outpatient program for eating disorder.

Detailed Description
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Subjects participating in this study will receive routine care for eating disorder at a partial hospitalization (PHP) level of care at MSHMC. In PHP, all patients have weekly medical screening visits for the duration of their time in care, as well as weekly individual therapy sessions, individual dietician sessions, and psychiatry appointments. They have supervised meals and numerous group therapy sessions. Every three weeks, patients in PHP complete a battery of mood and eating disorder indices including those evaluated in this study; participants in this study will complete an additional two surveys with this routine battery. Participants in this study will have no alterations in their routine eating disorder care outside of study article use and these additional surveys. Subjects will be enrolled at their first visit for eating disorder programming at child or adult partial hospitalization (PHP) programming at MSHMC adolescent medicine eating disorders clinic. Informed consent/assent will be obtained as described above. The subject will be provided with oral naltrexone or placebo weekly from the MSHMC research pharmacy. Subjects will be given one weeks' worth of medication at a time. Subjects will be randomized at enrollment to receive either study drug (naltrexone) or placebo. Participants or parents of minor participants will be provided study drug or placebo following completion of urine drug screen and consent/assent. Patients will take the medication daily for six weeks. For subjects who are enrolled in child PHP and who eat meals with parents, the families may choose to administer study drug during meals at programming. For adult patients enrolled in adult programming, subjects may choose to self-administer the medication. On their first contact with PHP, all patients in Child PHP complete various eating disorder indices as a part of routine care, including the ED-15, EDE-Q, RCMAS, CDI, GAD-7, and PHQ-9. This battery of indices is repeated every 3 weeks while a patient is in programming. For those who are enrolled in this study, they will complete their routine indices, in addition they will also complete the BIS/BAS and the ABUSI at enrollment and at weeks 3, 6, and 9 (after completion of medication) while in programming. Participants will receive routine eating disorder care while in PHP. Patients in Adult PHP typically complete a different inventory every three weeks. If a patient choses to participate in this study they will be asked to complete the same surveys as participants in Child PHP, and they will receive the same amount and type of compensation. Six months after enrollment, subjects will be sent copies of ED-15, EDE-Q, GAD-7, PHQ-9, BIS/BAS, and ABUSI indices either in an in-person medical appointment or via RedCap to complete. If the patient returns for medical follow-up between 5 and 7 months after enrollment, their height, weight, and body mass index will also be recorded to determine if weight restoration was maintained. At initial contact with the eating disorders clinic, all patients receive an initial battery of laboratory tests as a part of the standard of care for eating disorder. These tests include liver function assays and transaminase levels.

Official Title
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A Double-Blind Placebo-Controlled Evaluation of Effectiveness of Oral Naltrexone in Management of Adolescent Eating Disorders

Conditions
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Anorexia Nervosa/Bulimia, Anorexia in Adolescence, Anorexia Nervosa, Atypical, Anorexia Nervosa, Binge Eating/Purging Type, Purging (Eating Disorders), Impulsive Behavior, Eating Disorders, Bulimia Nervosa, Eating Disorders in Adolescence

Intervention / Treatment
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* Drug: Naltrexone Hydrochloride
* Other: Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ages 13-25 (inclusive) Any sex Diagnoses of anorexia nervosa binge-purge subtype, bulimia nervosa, purging disorder, or atypical anorexia nervosa with bingeing or purging behaviors according to the Diagnostic and Statistical Manual version 5 diagnostic criteria Electing to participate in child or adult partial hospitalization program for eating disorder treatment at MSHMC The diagnostic criteria for anorexia nervosa, binge-purge subtype, are: A. Restriction of energy intake relative to requirements, leading to a significantly low body weight in the context of age, sex, developmental trajectory, and physical health. Significantly low weight is defined as a weight that is less than minimally normal or, for children and adolescents, less than minimally expected. B. Intense fear of gaining weight or of becoming fat, or persistent behavior that interferes with weight gain, even though at a significantly low weight. C. Disturbance in the way in which one's body weight or shape is experienced, undue influence of body weight or shape on self-evaluation, or persistent lack of recognition of the seriousness of the current low body weight D. During the last three months the individual has engaged in recurrent episodes of binge eating or purging behaviour (i.e. self-induced vomiting, or the misuse of laxatives, diuretics, or enemas).19 E. A diagnosis of atypical anorexia nervosa can be made when the body weight is normal or high If these patients engage in bingeing or purging behaviors as defined in anorexia nervosa, binge-purge subtype, they are eligible for inclusion in this study The diagnostic criteria for bulimia nervosa are: A. Recurrent episodes of binge eating. An episode of binge eating is characterized by B. both: i. Eating in a discrete period of time (e.g. within any 2 hour period), an amount of food that is definitely larger than what most individuals would eat in a similar period of time under similar circumstances; ii. A sense of lack of control over eating during the episodes (e.g. a feeling that one cannot stop eating or control what or how much one is eating. C. Recurrent inappropriate compensatory behaviors to prevent weight gain, such as self-induced vomiting; misuse of laxatives, diuretics, or other medications; fasting; or excessive exercise. D. The binge eating and inappropriate compensatory behaviors both occur, on average, at least once a week for 3 months. E. Self-evaluation is unduly influenced by body shape and weight. F. The disturbance does not occur exclusively during episodes of anorexia nervosa. • The diagnostic criteria for purging disorder are: recurrent purging behavior to influence weight or shape (e.g. self-induced vomiting; misuse of laxatives, diuretics, or other medications) in the absence of binge eating. Exclusion Criteria: Diagnosis of intellectual disability History of known genetic or neurologic disease Need for treatment with opioid painkillers Weight <25kg Inability to swallow pills Lack of proficiency in written or spoken English Urine drug screen positive for opioids at enrollment Positive serum pregnancy test at enrollment Lactation Elevation of three times the upper limit of normal for age in either alanine aminotransferase (ALT) or asparagine aminotransferase (AST).High risk of suicide at enrollment on Columbia Suicide Severity Rating Scale (C-SSRS, for participants age 18-25) or Ask Suicide Screening Questions (ASQ, participants age 13 to 17)

Ages Eligible for Study
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Minimum Age: 13 Years
Maximum Age: 25 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: double-blind, placebo controlled randomized clinical trial
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>Oral naltrexone, to start as 25mg for three days then 50mg a day for 6 weeks. Oral naltrexone generic tabs will be blinded in opaque gelatin capsules with methylcellulose filler | Drug: Naltrexone Hydrochloride<br>* 25mg x 3 days then 50mg a day thereafter<br>|
| Placebo Comparator: Control<br>Opaque gelatin capsules with methylcellulose filler, taken by mouth once a day for six weeks | Other: Control<br>* Methylcellulose and gelatin capsule only<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ED-15 score | ED-15 is an evidenced-based metric of eating disorder symptom severity and frequency. | Time Frame: Measured at the following timepoints: enrollment | 
| ED-15 score | ED-15 is an evidenced-based metric of eating disorder symptom severity and frequency. | Time Frame: Measured at the following timepoints: one week | 
| ED-15 score | ED-15 is an evidenced-based metric of eating disorder symptom severity and frequency. | Time Frame: Measured at the following timepoints: three week | 
| ED-15 score | ED-15 is an evidenced-based metric of eating disorder symptom severity and frequency. | Time Frame: Measured at the following timepoints: six weeks | 
| ED-15 score | ED-15 is an evidenced-based metric of eating disorder symptom severity and frequency. | Time Frame: Measured at the following timepoints: nine weeks (last week of treatment) | 
| ED-15 score | ED-15 is an evidenced-based metric of eating disorder symptom severity and frequency. | Time Frame: Measured at the following timepoints: 6 months after enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Eating Disorder Examination Questionnaire score (EDE-Q) | EDE-Q is an evidence-based metric of eating disorder severity | Measured at the following timepoints: enrollment | 
| Eating Disorder Examination Questionnaire score (EDE-Q) | EDE-Q is an evidence-based metric of eating disorder severity | Measured at the following timepoints: one week | 
| Eating Disorder Examination Questionnaire score (EDE-Q) | EDE-Q is an evidence-based metric of eating disorder severity | Measured at the following timepoints: three weeks | 
| Eating Disorder Examination Questionnaire score (EDE-Q) | EDE-Q is an evidence-based metric of eating disorder severity | Measured at the following timepoints: six weeks | 
| Eating Disorder Examination Questionnaire score (EDE-Q) | EDE-Q is an evidence-based metric of eating disorder severity | Measured at the following timepoints: nine weeks (last week of treatment) | 
| Eating Disorder Examination Questionnaire score (EDE-Q) | EDE-Q is an evidence-based metric of eating disorder severity | Measured at the following timepoints: 6 months after enrollment | 
| Patient Health Questionnaire score (PHQ-9) | Evidence-based metric of depression, min = 0, max= 27, higher scores indicate more severe depression | Measured at the following timepoints: enrollment | 
| Patient Health Questionnaire score (PHQ-9) | Evidence-based metric of depression, min = 0, max= 27, higher scores indicate more severe depression | Measured at the following timepoints: one week | 
| Patient Health Questionnaire score (PHQ-9) | Evidence-based metric of depression, min = 0, max= 27, higher scores indicate more severe depression | Measured at the following timepoints: three weeks | 
| Patient Health Questionnaire score (PHQ-9) | Evidence-based metric of depression, min = 0, max= 27, higher scores indicate more severe depression | Measured at the following timepoints: six weeks | 
| Patient Health Questionnaire score (PHQ-9) | Evidence-based metric of depression, min = 0, max= 27, higher scores indicate more severe depression | Measured at the following timepoints: nine weeks (last week of treatment) | 
| Patient Health Questionnaire score (PHQ-9) | Evidence-based metric of depression, min = 0, max= 27, higher scores indicate more severe depression | Measured at the following timepoints: 6 months after enrollment | 
| Generalized Anxiety Disorder Screener score (GAD-7) | evidence-based metric of anxiety, min=0, max=21, higher scores indicate more severe anxiety | Measured at the following timepoints: enrollment | 
| Generalized Anxiety Disorder Screener score (GAD-7) | evidence-based metric of anxiety, min=0, max=21, higher scores indicate more severe anxiety | Measured at the following timepoints: one week | 
| Generalized Anxiety Disorder Screener score (GAD-7) | evidence-based metric of anxiety, min=0, max=21, higher scores indicate more severe anxiety | Measured at the following timepoints: three weeks | 
| Generalized Anxiety Disorder Screener score (GAD-7) | evidence-based metric of anxiety, min=0, max=21, higher scores indicate more severe anxiety | Measured at the following timepoints: six weeks | 
| Generalized Anxiety Disorder Screener score (GAD-7) | evidence-based metric of anxiety, min=0, max=21, higher scores indicate more severe anxiety | Measured at the following timepoints: nine weeks (last week of treatment) | 
| Generalized Anxiety Disorder Screener score (GAD-7) | evidence-based metric of anxiety, min=0, max=21, higher scores indicate more severe anxiety | Measured at the following timepoints: 6 months after enrollment | 
| Alexian Brothers Urge to Self-Injure Scale (ABUSI) | evidence-based metric of urge to self-harm | Measured at the following timepoints: enrollment | 
| Alexian Brothers Urge to Self-Injure Scale (ABUSI) | evidence-based metric of urge to self-harm | Measured at the following timepoints: one week | 
| Alexian Brothers Urge to Self-Injure Scale (ABUSI) | evidence-based metric of urge to self-harm | Measured at the following timepoints: three weeks | 
| Alexian Brothers Urge to Self-Injure Scale (ABUSI) | evidence-based metric of urge to self-harm | Measured at the following timepoints: six weeks | 
| Alexian Brothers Urge to Self-Injure Scale (ABUSI) | evidence-based metric of urge to self-harm | Measured at the following timepoints: nine weeks (last week of treatment) | 
| Alexian Brothers Urge to Self-Injure Scale (ABUSI) | evidence-based metric of urge to self-harm | Measured at the following timepoints: 6 months after enrollment | 
| Behavioral Inhibition System/Behavioral Activation System score (BIS/BAS) | Evidence-based metric of impulsivity | Measured at the following timepoints: enrollment | 
| Behavioral Inhibition System/Behavioral Activation System score (BIS/BAS) | Evidence-based metric of impulsivity | Measured at the following timepoints: one week | 
| Behavioral Inhibition System/Behavioral Activation System score (BIS/BAS) | Evidence-based metric of impulsivity | Measured at the following timepoints: three weeks | 
| Behavioral Inhibition System/Behavioral Activation System score (BIS/BAS) | Evidence-based metric of impulsivity | Measured at the following timepoints: six weeks | 
| Behavioral Inhibition System/Behavioral Activation System score (BIS/BAS) | Evidence-based metric of impulsivity | Measured at the following timepoints: nine weeks (last week of treatment) | 
| Behavioral Inhibition System/Behavioral Activation System score (BIS/BAS) | Evidence-based metric of impulsivity | Measured at the following timepoints: 6 months after enrollment | 
| Rate of weight restoration | For participants who need to restore weight, will evaluate the rate of weight gain in care | Will evaluate total rate of weight restoration via chart review at the end of the study | 
| Rate of weight restoration | For participants who need to restore weight, will evaluate the rate of weight gain in care | Will evaluate total rate of weight restoration via chart review 6 months after enrollment | 
| Need For Higher Level of Care | Need to leave the current level of care (where the study is being conducted) to go to a residential, inpatient, or hospital facility | Will evaluate total rate of weight restoration via chart review at the end of the study | 
| Need For Higher Level of Care | Need to leave the current level of care (where the study is being conducted) to go to a residential, inpatient, or hospital facility | Will evaluate total rate of weight restoration via chart review 6 months after enrollment |