ONPED: Oral Naltrexone In Pediatric Eating Disorders

Sponsor

Rosemary Claire Roden (Other)

Overall Status

Enrolling by invitation

CT.gov ID

NCT05073679

Collaborator

Children's Miracle Network (Other)

Enrollment

Location

Arms

15.3

Anticipated Duration (Months)

3.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
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	Drug: Naltrexone Hydrochloride Other: Control	Phase 2/Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

double-blind, placebo controlled randomized clinical trialdouble-blind, placebo controlled randomized clinical trial

Masking:

Triple (Participant, Care Provider, Investigator)

Masking Description:

The Penn State Health IDS pharmacy will purchase Naltrexone 50mg tablets from a pharmaceutical wholesaler. The IDS pharmacy will purchase gelatin capsules and USP grade methylcellulose from a pharmacy supplier to be used for compounding the active and placebo capsules. For the active Naltrexone 50mg capsules, a Naltrexone 50mg tablet will be placed in an empty gelatin capsule with methylcellulose filler. The placebo capsules will be empty gelatin capsules filled with Methylcellulose. Participants will be randomized using redcap at enrollment to either study article or placebo, and neither investigators nor care providers will be aware of which article the participants receive.

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Apr 22, 2022

Anticipated Primary Completion Date :

May 1, 2023

Anticipated Study Completion Date :

Aug 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intervention Oral naltrexone, to start as 25mg for three days then 50mg a day thereafter for up to nine weeks or completion of higher level of care, whichever haver happens first. 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 nine weeks or until completion of higher level of care, whichever happens first	Other: Control Methylcellulose and gelatin capsule only

Arm

Intervention/Treatment

Experimental: Intervention

Oral naltrexone, to start as 25mg for three days then 50mg a day thereafter for up to nine weeks or completion of higher level of care, whichever haver happens first. 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 nine weeks or until completion of higher level of care, whichever happens first

Other: Control

Methylcellulose and gelatin capsule only

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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

Other Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

13 Years to 25 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

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.
Intense fear of gaining weight or of becoming fat, or persistent behavior that interferes with weight gain, even though at a significantly low weight.
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:

Recurrent episodes of binge eating. An episode of binge eating is characterized by

B. both:

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.

Recurrent inappropriate compensatory behaviors to prevent weight gain, such as self-induced vomiting; misuse of laxatives, diuretics, or other medications; fasting; or excessive exercise.
The binge eating and inappropriate compensatory behaviors both occur, on average, at least once a week for 3 months.
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)