Cognitive-Behavioral and Pharmacologic (LDX) Treatment of Binge-Eating Disorder and Obesity: Medication Change for Non-Responders

Study Overview
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Brief Summary
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This study will test the relative efficacy and effectiveness of the combination of naltrexone and bupropion (NB) medication as a treatment for binge-eating disorder (BED) in patients with obesity. This is a controlled test of whether, amongst non-responders to acute treatments, NB medication results in superior outcomes compared with placebo.

Detailed Description
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Obesity is a heterogeneous problem and research has highlighted the particular significance of a subgroup with binge-eating disorder (BED), the most prevalent formal eating disorder. Improved treatments for patients with obesity and BED are needed that can produce sustained clinical outcomes and promote weight loss. This study RCT will provide new and novel findings from a controlled test, amongst non-responders to acute treatments, whether Naltrexone/Bupropion medication results in superior and longer-term outcomes than placebo.

Official Title
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Cognitive-Behavioral and Pharmacologic Treatment of Binge-Eating Disorder and Obesity

Conditions
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Binge-Eating Disorder, Obesity

Intervention / Treatment
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* Drug: Naltrexone and Bupropion
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 to 64 years old Meets DSM-5 criteria for binge-eating disorder BMI 27-30 with a controlled obesity-related co-morbidity; or BMI ≥ 30 and <50 Medically cleared as determined by EKG and medical record review Available for the duration of the treatment and follow-up (18 months) Read, comprehend, and write English at a sufficient level to complete study-related materials Able to travel to study location (New Haven, CT) for weekly visits Exclusion Criteria: Previous history of problems with LDX or other stimulants Current psychostimulant use or use of any medication for ADHD Current use of study medications: LDX (Vyvanse), Bupropion (Wellbutrin, Zyban), Naltrexone, or Contrave History of congenital heart disease, known structural cardiac abnormalities, cardiomyopathy, serious heart arrhythmia, coronary artery disease, cerebrovascular pathology including stroke, exertional chest pain, uncontrolled high blood pressure, and other serious heart problems. History of severe renal, hepatic, neurological, or chronic pulmonary disease or other serious, unstable medical disorder. Current uncontrolled hypertension Current uncontrolled type I or II diabetes mellitus Current uncontrolled thyroid illness Gallbladder disease Co-occurring severe mental illness requiring hospitalization or intensive treatment Endorses current active suicidal or homicidal ideation with intent or plan History or current alcohol or substance use disorder (smoking is not exclusionary) Predisposition to seizures History of anorexia nervosa or bulimia nervosa, or currently regularly self-inducing vomiting Currently taking MAOI, SSRI or strong inhibitors of CYP2D6 History of allergy or sensitivity to the study medication or stimulant medications Current use of medications contraindicated with the study medications Currently breast feeding or pregnant, or not willing to use reliable form of contraception Currently taking opioid pain medications or drugs Currently using effective treatment (evidence-based therapeutic or psychopharmacologic) for eating and/or weight loss Currently participating in another clinical study in which the participant is or will be exposed to an investigational or a non-investigational drug or device Medical status judged by study physician as contraindication

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Naltrexone/Bupropion<br> | Drug: Naltrexone and Bupropion<br>* Participants randomly assigned to this arm will receive 12 weeks of Naltrexone and Bupropion medication.<br>|
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* Participants randomly assigned to this arm will receive 12 weeks of an inactive placebo.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Binge-Eating Frequency | Binge-eating frequency is a continuous variable of binge-eating episodes assessed using interview (Eating Disorder Examination interview). The Eating Disorder Examination uses a 28 day recall of eating behavior. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM -5) defines binge-eating as eating, in a discrete period of time an amount of food that is definitely larger than most people would eat during a similar period of time and under similar circumstances and a sense of loss of control over eating during the episode. The number of episodes that meet this description will be counted and totaled. | From baseline interview at study enrollment to 3 months after the 12-week treatment. | 
| Binge-Eating Frequency | Binge-eating frequency is a continuous variable of binge-eating episodes assessed using interview (Eating Disorder Examination interview). The Eating Disorder Examination uses a 28 day recall of eating behavior. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM -5) defines binge-eating as eating, in a discrete period of time an amount of food that is definitely larger than most people would eat during a similar period of time and under similar circumstances and a sense of loss of control over eating during the episode. The number of episodes that meet this description will be counted and totaled. | From post-treatment to the 6-month follow-up | 
| Binge-Eating Frequency | Binge-eating frequency is a continuous variable of binge-eating episodes assessed using interview (Eating Disorder Examination interview). The Eating Disorder Examination uses a 28 day recall of eating behavior. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM -5) defines binge-eating as eating, in a discrete period of time an amount of food that is definitely larger than most people would eat during a similar period of time and under similar circumstances and a sense of loss of control over eating during the episode. The number of episodes that meet this description will be counted and totaled. | From post-treatment to the 12-month follow-up | 
| Body Mass Index | Body Mass Index is calculated using measured height and weight (e.g., percent loss). | From baseline interview at study enrollment to 3 months after the 12-week treatment. | 
| Body Mass Index | Body Mass Index is calculated using measured height and weight (e.g., percent loss). | From post-treatment to the 6-month follow-up | 
| Body Mass Index | Body Mass Index is calculated using measured height and weight (e.g., percent loss). | From post-treatment to the 12-month follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Binge-Eating Remission | Categorical: zero binges/28 days | From baseline interview at study enrollment to 3 months after the 12-week treatment. | 
| Binge-Eating Remission | Categorical: zero binges/28 days | From post-treatment to the 6-month follow-up | 
| Binge-Eating Remission | Categorical: zero binges/28 days | From post-treatment to the 12-month follow-up | 
| Eating-Disorder Psychopathology (Continuous) | Eating-disorder psychopathology is a continuous variable as assessed by the global score of the Eating Disorder Examination/Eating Disorder Examination-Questionnaire. Scores range from 0-6 (0=no eating-disorder psychopathology; 6=severe eating-disorder psychopathology). | From baseline interview at study enrollment to 3 months after the 12-week treatment. | 
| Eating-Disorder Psychopathology (Continuous) | Eating-disorder psychopathology is a continuous variable as assessed by the global score of the Eating Disorder Examination/Eating Disorder Examination-Questionnaire. Scores range from 0-6 (0=no eating-disorder psychopathology; 6=severe eating-disorder psychopathology). | From post-treatment to the 6-month follow-up | 
| Eating-Disorder Psychopathology (Continuous) | Eating-disorder psychopathology is a continuous variable as assessed by the global score of the Eating Disorder Examination/Eating Disorder Examination-Questionnaire. Scores range from 0-6 (0=no eating-disorder psychopathology; 6=severe eating-disorder psychopathology). | From post-treatment to the 12-month follow-up | 
| Depressive Symptoms | Depressive symptoms is a continuous variable of depressive symptomatology as assessed by the self-report measure, the Beck Depression Inventory - Second Edition. Scores range from 0-63 (0=no depressive symptoms, 63=greater depressive symptoms). | From baseline interview at study enrollment to 3 months after the 12-week treatment. | 
| Depressive Symptoms | Depressive symptoms is a continuous variable of depressive symptomatology as assessed by the self-report measure, the Beck Depression Inventory - Second Edition. Scores range from 0-63 (0=no depressive symptoms, 63=greater depressive symptoms). | From post-treatment to the 6-month follow-up | 
| Depressive Symptoms | Depressive symptoms is a continuous variable of depressive symptomatology as assessed by the self-report measure, the Beck Depression Inventory - Second Edition. Scores range from 0-63 (0=no depressive symptoms, 63=greater depressive symptoms). | From post-treatment to the 12-month follow-up |