Abstract
BackgroundThe efficacy and safety of Lisdexamfetamine dimesylate (LDX) in the treatment of moderate to severe binge eating disorder (BED) has been demonstrated in multiple randomised clinical trials. Despite this, little is known about how LDX acts to improve binge eating symptoms. This study aims to provide a comprehensive understanding of the neural mechanisms by which LDX improves symptoms of BED. We hypothesise that LDX will act by normalising connectivity within neural circuits responsible for reward and impulse control, and that this normalisation will correlate with reduced binge eating episodes.MethodsThis is an open-label Phase 4 clinical trial of LDX in adults with moderate to severe BED. Enrolment will include 40 adults with moderate to severe BED aged 18–40 years and Body Mass Index (BMI) of 20–45 kg/m2, and 22 healthy controls matched for age, gender and BMI. Clinical interview and validated scales are used to confirm diagnosis and screen for exclusion criteria, which include comorbid anorexia nervosa or bulimia nervosa, use of psychostimulants within the past 6 months, and current use of antipsychotics or noradrenaline reuptake inhibitors. Baseline assessments include clinical symptoms, multimodal neuroimaging, cognitive assessment of reward sensitivity and behavioural inhibition, and an (optional) genetic sample. A subset of these assessments are repeated after eight weeks of treatment with LDX titrated to either 50 or 70 mg. The primary outcome measures are resting-state intrinsic connectivity and the number of binge eating episodes. Analyses will be applied to resting-state fMRI data to characterise pharmacological effects across the functional connectome, and assess correlations with symptom measure changes. Comparison of neural measures between controls and those with BED post-treatment will also be performed to determine whether LDX normalises brain function.DiscussionFirst enrolment was in May 2018, and is ongoing. This study is the first comprehensive investigation of the neurobiological changes that occur with LDX treatment in adults with moderate to severe BED.Trial registrationACTRN12618000623291, Australian and New Zealand Clinical Trials Registry URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374913&isReview=true. Date of Registration: 20 April 2018.
Highlights
The efficacy and safety of Lisdexamfetamine dimesylate (LDX) in the treatment of moderate to severe binge eating disorder (BED) has been demonstrated in multiple randomised clinical trials
Binge Eating Disorder (BED) is an eating disorder characterised by recurrent episodes of excessive eating with a sense of lack of control over eating
The primary aim of this study is to provide a comprehensive understanding of the neural mechanisms by which LDX improves symptoms of BED
Summary
The efficacy and safety of Lisdexamfetamine dimesylate (LDX) in the treatment of moderate to severe binge eating disorder (BED) has been demonstrated in multiple randomised clinical trials. In a positron emission tomography (PET) study, high Body Mass Index (BMI) individuals with BED were found to have significantly increased DA levels in the caudate and putamen in response to food stimuli, relative to high BMI individuals without BED [6] This significantly correlated with binge eating severity but not with BMI. Functional magnetic resonance imaging (fMRI) studies have broadly shown dysfunction in the fronto-striatal regions relating to reward and inhibition [7,8,9,10,11,12] Those with BED may have impaired flexibility in reward-based decision making, with reduced activation in regions implicated in goaldirected action and evaluation of reward-based choice such the bilateral anterior insula and ventro-lateral prefrontal cortex [13]. Despite these important insights into the neuropathophysiology of BED, more studies are required to better understand neural dysfunction in BED, and how pharmacotherapies influence these systems to reduce BED symptoms
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