Vortioxetine for Binge Eating Disorder

Study Overview
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Brief Summary
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The aim of the present study is to examine the efficacy and safety of vortioxetine vs placebo in adults with moderate to severe Binge eating disorder, as indicated by at least 3 binge eating days per week for the 2 weeks before the baseline visit.

Detailed Description
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Binge-eating disorder recently included in the Diagnostic and Statistical Manual, 5th Edition, is now recognized as a serious public health problem. Binge-eating disorder is associated with obesity and psychiatric comorbidities, including depression, and may be predictive of metabolic syndrome. Many patients are undertreated despite functional impairments and personal and social difficulties leading to a poor quality of life. Binge-eating disorder is characterized by recurrent episodes of excessive food consumption accompanied by a sense of loss of control and psychological distress but without the inappropriate compensatory weight-loss behaviors of bulimia nervosa. Binge eating is seen in 23-46% of obese individuals seeking weight loss treatment and its severity relates to body mass index and predicts regain of lost weight. Current treatments for binge eating disorder are often inadequate. Cognitive behavioral therapy has been shown to reduce binge eating but finding trained psychologists is difficult. Lisdexamfetamine was recently approved by the Food and Drug Administration for binge eating disorder but it carries risk of addiction and diversion and so will likely not be prescribed by most family physicians or psychiatrists. Other currently available medications, used off-label for binge eating disorder, include anticonvulsants, which may reduce binge eating but are often poorly tolerated. Therefore, additional clinical trials are needed to identify effective pharmacotherapies. Consuming food is necessary for life and involves brain regions that are quite ancient in evolutionary terms. The intestinal tract itself is almost like a second brain in that it contains vast amounts of neurons used to transmit and process sensory information; indeed the intestinal tract contains more of the neurotransmitter serotonin than the brain itself. Peripheral signals from the body (including from the intestinal tract, but also from the blood stream - e.g. glucose levels) are transmitted to brain regions such as the hypothalamic nuclei to help regulate appetite/hunger and maintain equilibrium. Another key aspect of circuitry involved in eating involves the brain reward system, including the nucleus accumbens, which is regulated by neurotransmitters such as dopamine, opioids, noradrenaline, and serotonin. In humans, but to a lesser degree in other animals, there is also top-down control from the prefrontal cortices, which serve to regulate our behaviors and suppress our tendencies to crave rewards, and allow us to flexibly adapt our behavior rather than get stuck in repetitive habits. Thus, binge-eating most likely involves dysregulation of all three above domains regulating behavior: the primitive 'peripheral-hypothalamic' feedback system, reward circuitry, and top-down control circuitry. On a neurochemical level, binge eating may be related to dysfunction of the serotonergic, dopamine, glutamatergic, and norepinephrine systems. Thus, a medication to target binge eating needs to be multi-modal in terms of its pharmacology.

Official Title
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A Double-Blind, Placebo-Controlled Study of Vortioxetine in the Treatment of Binge Eating Disorder

Conditions
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Binge Eating Disorder

Intervention / Treatment
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* Drug: Vortioxetine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women age 18-65; Primary diagnosis of Binge eating disorder; At least 3 binge eating days per week for the 2 weeks before the baseline visit; Ability to understand and sign the consent form. Exclusion Criteria: Unstable medical illness based on history or clinically significant abnormalities on baseline physical examination (history of medical illness which is currently stable is allowed such as diabetes well controlled, treated hypothyroidism, hypertension, etc) Current pregnancy or lactation, or inadequate contraception in women of childbearing potential Subjects considered an immediate suicide risk based on the Columbia Suicide Severity rating Scale (C-SSRS) (www.cssrs.columbia.edu/docs) Past 12-month DSM-5 major psychiatric disorder (psychotic disorder, bipolar disorder, major depressive disorder) Past 6-month alcohol or substance use disorders Illegal substance use based on urine toxicology screening Initiation of psychological or weight-loss interventions within 3 months of screening Use of any other prescription psychotropic medication (except an as needed hypnotic or as needed benzodiazepine) Previous treatment with Vortioxetine Currently taking over the counter weight loss medications. If willing to stop these medications, the participant will not be excluded based on this criterion. 10) Cognitive impairment that interferes with the capacity to understand and self-administer medication or provide written informed consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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 |
| --- | --- |
| Placebo Comparator: Placebo<br>10 milligrams per day for the first week and 10 milligrams per day for the final taper week 20 milligrams per day for 10 weeks between taper periods. | Drug: Placebo<br> <br> |
| Experimental: Vortioxetine<br>10 milligrams per day day for the first week and 10 milligrams per day for the final taper week 20 milligrams per day for 10 weeks between taper periods. | Drug: Vortioxetine<br>* Medication currently approved for major depression.<br>* Other names: Brintellix;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Number of Binge Eating Episodes | Subjects will report the number of binge eating episodes in the week preceding the final visit (Week 12 of treatment), both to the investigator and via daily eating journals at all 9 visits. The outcome measure was the change in number of episodes from Week 0 (baseline) to the final visit (Week 12). | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BMI | Assessment of change in patient body mass index over the course of the study (from baseline to the final visit at Week 12). | 12 weeks | 
| Number of Participants With 4-week Cessation From Binge Eating | Subjects will be assessed at 4 weeks to determine cessation of binge eating status. | 4 weeks | 
| Clinical Global Impression Improvement Scale (CGI) | Patient global improvement relative to baseline, with scores ranging from 1-7. Higher scores indicate the patient is doing severely worse than they were at the beginning of treatment. | Week 12 (final) visit | 
| Three-Factor Eating Questionnaire | A self-reported measure of binge eating behavior that will be collected at all 9 study visits with scores ranging from 0-51, with higher scores indicating more compulsive eating habits. | 12 weeks | 
| Yale-Brown Obsessive Compulsive Scale Modified for Binge Eating | A clinician-administered scale assessing binge eating severity that will be assessed at all 9 study visits. Scores range from 0-40 with higher scores indicating more severe OCD symptoms. | 12 weeks | 
| Quality of Life Inventory | A self-report assessment of patient perceived quality of life that will be assessed at baseline and final visit. The scale provides a discrete score ranging from -192 to 192, with higher numbers indicating higher subjective quality of life. | 12 weeks | 
| Hamilton Depression Rating Scale | A clinician-administered assessment of depression that will be assessed at all 8 study visits after the baseline visit. The scale provides a discrete score that ranges from 0-52, with higher scores indicating more severe depressive symptoms. | 12 weeks | 
| Hamilton Anxiety Rating Scale | A clinician-administered assessment of anxiety that will be assessed at all 9 study visits. The scale provides a discrete score that ranges from 0-56, with higher scores indicating more severe anxiety symptoms. | 12 weeks |