Cognitive-Behavioral and Pharmacologic (LDX) Treatment of Binge-Eating Disorder and Obesity: Acute Treatment

Study Overview
=================
Brief Summary
-----------------
Brief Summary: This study will compare the effectiveness of cognitive behavioral therapy (CBT), lisdexamfetamine (LDX), and the combination of CBT and LDX for the treatment of binge-eating disorder in patients with obesity. This is an acute treatment comparing CBT or LDX alone or in combination.

Detailed Description
-----------------
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. This study examined the effectiveness of two leading but distinct treatments - lisdexamfetamine (LDX) and cognitive behavioral therapy (CBT) - alone and in combination, for BED in patients with obesity. LDX is the first and only FDA-approved medication for the treatment of BED and has demonstrated short-term effectiveness relative to placebo. CBT is the best-established psychological treatment, has demonstrated short-term effectiveness and treatment specificity (i.e., superiority to a variety of control and active treatments), has shown longer-term superiority to fluoxetine, and longer-term durability of outcomes. N=180 participants with BED and obesity will be randomly assigned to one of three interventions, CBT alone, LDX alone, or CBT combined with LDX. This RCT will provide new findings regarding the relative effectiveness of LDX, CBT, and combined CBT+LDX for patients with obesity and BED. No such study has been performed.

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

Conditions
-----------------
Binge-Eating Disorder, Obesity

Intervention / Treatment
-----------------
* Drug: Lisdexamfetamine Dimesylate
* Behavioral: Cognitive-Behavioral Therapy
* Other: Combination LDX and Cognitive-Behavioral Therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
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
-----------------
Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: LDX<br> | Drug: Lisdexamfetamine Dimesylate<br>* Participants randomly assigned to this arm will receive 12 weeks of LDX medication.<br>|
| Active Comparator: Cognitive-Behavioral Therapy<br> | Behavioral: Cognitive-Behavioral Therapy<br>* Participants randomly assigned to this arm will receive 12 weeks of Cognitive-Behavioral Therapy<br>|
| Active Comparator: LDX and Cognitive Behavioral Therapy<br> | Other: Combination LDX and Cognitive-Behavioral Therapy<br>* Participants randomly assigned to this arm will receive 12 weeks of LDX and Cognitive-Behavioral Therapy<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Binge-Eating Frequency | Binge eating will be assessed by interview and self-report and the primary outcomes is frequency. Frequency will be defined continuously (analyzed dimensionally). | Post-treatment (3 months) | 
| Body Mass Index | BMI is calculated using measured height and weight (e.g., percent loss). | Post-treatment (3 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Binge-Eating Remission | Categorical: zero binges/28 days | Post-treatment (3 months) | 
| Eating-Disorder Psychopathology | 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). | Post-treatment (3 months) | 
| 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). | Post-treatment (3 months) |