Oral Naltrexone In Pediatric Eating Disorders (ONPED)

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

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Bulimia Nervosa; Impulsive Behavior; Purging (Eating Disorders); Eating Disorders; Eating Disorders in Adolescence; Anorexia Nervosa/Bulimia; Anorexia in Adolescence; Anorexia Nervosa, Atypical; Anorexia Nervosa, Binge Eating/Purging Type
• Intervention / Treatment: Drug: Naltrexone Hydrochloride; Other: Control

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Milton S. Hershey Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years to 25 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; 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; 25mg x 3 days then 50mg a day thereafter
Placebo Comparator: Control; Opaque gelatin capsules with methylcellulose filler, taken by mouth once a day for six weeks	Other: Control; Methylcellulose and gelatin capsule only

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Columbia Suicide Severity Rating Scale (CSSRS)	Evidence-based metric evaluating for presence of suicidal ideation and severity	enrollment for patients age 17 or older
Columbia Suicide Severity Rating Scale (CSSRS)	Evidence-based metric evaluating for presence of suicidal ideation and severity	week 1 for patients age 17 or older
Columbia Suicide Severity Rating Scale (CSSRS)	Evidence-based metric evaluating for presence of suicidal ideation and severity	week 2 for patients age 17 or older
Columbia Suicide Severity Rating Scale (CSSRS)	Evidence-based metric evaluating for presence of suicidal ideation and severity	week 3 for patients age 17 or older
Columbia Suicide Severity Rating Scale (CSSRS)	Evidence-based metric evaluating for presence of suicidal ideation and severity	week 4 for patients age 17 or older
Columbia Suicide Severity Rating Scale (CSSRS)	Evidence-based metric evaluating for presence of suicidal ideation and severity	week 5 for patients age 17 or older
Columbia Suicide Severity Rating Scale (CSSRS)	Evidence-based metric evaluating for presence of suicidal ideation and severity	week 6 for patients age 17 or older
Columbia Suicide Severity Rating Scale (CSSRS)	Evidence-based metric evaluating for presence of suicidal ideation and severity	week 7 for patients age 17 or older
Columbia Suicide Severity Rating Scale (CSSRS)	Evidence-based metric evaluating for presence of suicidal ideation and severity	week 8 for patients age 17 or older
Columbia Suicide Severity Rating Scale (CSSRS)	Evidence-based metric evaluating for presence of suicidal ideation and severity	week 9 for patients age 17 or older
Columbia Suicide Severity Rating Scale (CSSRS)	Evidence-based metric evaluating for presence of suicidal ideation and severity	6 months after enrollment for patients age 17 or older
Ask Suicide Screening Questions (ASQ)	Evidence-based metric evaluating for presence of suicidal ideation and severity	enrollment for patients age 16 or younger
Ask Suicide Screening Questions (ASQ)	Evidence-based metric evaluating for presence of suicidal ideation and severity	week 1 for patients age 16 or younger
Ask Suicide Screening Questions (ASQ)	Evidence-based metric evaluating for presence of suicidal ideation and severity	week 2 for patients age 16 or younger
Ask Suicide Screening Questions (ASQ)	Evidence-based metric evaluating for presence of suicidal ideation and severity	week 3 for patients age 16 or younger
Ask Suicide Screening Questions (ASQ)	Evidence-based metric evaluating for presence of suicidal ideation and severity	week 4 for patients age 16 or younger
Ask Suicide Screening Questions (ASQ)	Evidence-based metric evaluating for presence of suicidal ideation and severity	week 5 for patients age 16 or younger
Ask Suicide Screening Questions (ASQ)	Evidence-based metric evaluating for presence of suicidal ideation and severity	week 6 for patients age 16 or younger
Ask Suicide Screening Questions (ASQ)	Evidence-based metric evaluating for presence of suicidal ideation and severity	week 7 for patients age 16 or younger
Ask Suicide Screening Questions (ASQ)	Evidence-based metric evaluating for presence of suicidal ideation and severity	week 8 for patients age 16 or younger
Ask Suicide Screening Questions (ASQ)	Evidence-based metric evaluating for presence of suicidal ideation and severity	week 9 for patients age 16 or younger
Ask Suicide Screening Questions (ASQ)	Evidence-based metric evaluating for presence of suicidal ideation and severity	6 months after enrollment for patients age 16 or younger

Collaborators and Investigators

• Sponsor: Rosemary Claire Roden
• Collaborators: Children's Miracle Network
• Investigators: Principal Investigator: Rosemary C Roden, MD, PennState Health Children's Hospital

Publications and helpful links

General Publications

• Posner K, Brown GK, Stanley B, Brent DA, Yershova KV, Oquendo MA, Currier GW, Melvin GA, Greenhill L, Shen S, Mann JJ. The Columbia-Suicide Severity Rating Scale: initial validity and internal consistency findings from three multisite studies with adolescents and adults. Am J Psychiatry. 2011 Dec;168(12):1266-77. doi: 10.1176/appi.ajp.2011.10111704.
• Tatham M, Turner H, Mountford VA, Tritt A, Dyas R, Waller G. Development, psychometric properties and preliminary clinical validation of a brief, session-by-session measure of eating disorder cognitions and behaviors: The ED-15. Int J Eat Disord. 2015 Nov;48(7):1005-15. doi: 10.1002/eat.22430. Epub 2015 May 26.
• Fairburn CG, Beglin SJ. Assessment of eating disorders: interview or self-report questionnaire? Int J Eat Disord. 1994 Dec;16(4):363-70.
• Horowitz LM, Bridge JA, Teach SJ, Ballard E, Klima J, Rosenstein DL, Wharff EA, Ginnis K, Cannon E, Joshi P, Pao M. Ask Suicide-Screening Questions (ASQ): a brief instrument for the pediatric emergency department. Arch Pediatr Adolesc Med. 2012 Dec;166(12):1170-6. doi: 10.1001/archpediatrics.2012.1276.
• Smucker MR, Craighead WE, Craighead LW, Green BJ. Normative and reliability data for the Children's Depression Inventory. J Abnorm Child Psychol. 1986 Mar;14(1):25-39. doi: 10.1007/BF00917219.
• Campbell K, Peebles R. Eating disorders in children and adolescents: state of the art review. Pediatrics. 2014 Sep;134(3):582-92. doi: 10.1542/peds.2014-0194.

Helpful Links

• Oral naltrexone package insert

Study record dates

Study Major Dates

• Study Start (Actual): April 22, 2022
• Primary Completion (Estimated): April 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: July 19, 2021
• First Submitted That Met QC Criteria: October 4, 2021
• First Posted (Actual): October 11, 2021

Study Record Updates

• Last Update Posted (Actual): August 16, 2023
• Last Update Submitted That Met QC Criteria: August 15, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Signs and Symptoms, Digestive; Hyperphagia; Anorexia; Anorexia Nervosa; Bulimia; Feeding and Eating Disorders; Bulimia Nervosa; Impulsive Behavior; Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Narcotic Antagonists; Alcohol Deterrents; Naltrexone
• Other Study ID Numbers: STUDY00014382; 150408 (Other Identifier: Food and Drug Administration)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No participant data is planned to be shared at the moment to protect patient privacy, as participants are all enrolled in a partial hospitalization program for mental health conditions.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No