Pilot Study of Startle-response Test to Assess Transcranial Direct Current Stimulation-induced Modulation of Hyperphagia in Prader-Willi Syndrome

Study Overview
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Brief Summary
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The purpose of this study is to determine the effects of transcranial direct current stimulation (tDCS) as it modifies hyperphagia in obese subjects, non-obese subjects, and subjects with Prader-Willi syndrome (PWS).

Detailed Description
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PWS is characterized by hypotonia, feeding difficulties, developmental delay and failure to thrive during infancy, and by an insatiable appetite (hyperphagia), rapid weight gain and obesity in early childhood. Hyperphagia is one of the most prominent and debilitating features of PWS, and currently no pharmaceutical drug has been successful in decreasing appetite in such patients. tDCS is a safe, noninvasive method whereby a weak electric current is directly transmitted into the brain via external electrodes connected to a 9-volt radio battery. It is based on decades-old observations that nerve cell firing can be altered by low amplitude direct current (DC). The researchers in this study believe that tDCS may have a positive impact on hyperphagia and weight. In this study, the investigators intend to assess whether the effects tDCS differ between obese subjects, non-obese subjects, and subjects with Prader-Willi syndrome by measuring the amplitude and latency of eyeblink startle responses to a set of food- and non-food-related visual stimuli in all subjects, various hyperphagia questionnaires, and cognitive and behavioral assessments. It is hypothesized that as a group, subjects with Prader-Willi syndrome will demonstrate behavioral and psychometric evidence of abnormal food image processing, craving and associated behaviors relative to our control groups, and this group may receive potentially beneficial effects from tDCS sessions. Obese subjects are also predicted to have decreased hyperphagia and food cravings as a result of tDCS.

Official Title
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Pilot Study of Startle-response Test to Assess Transcranial Direct Current Stimulation- Induced Modulation of Hyperphagia in Prader-Willi Syndrome

Conditions
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Hyperphagia, Prader-Willi Syndrome

Intervention / Treatment
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* Device: tDCS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy individuals and individuals diagnosed with Prader-Willi syndrome Provide informed consent to participate in the study Body Mass Index (BMI) <25kg/m2 (for non-obese subjects only) Body Mass Index (BMI) ≥30kg/m2 (for obese subjects only) Exclusion Criteria: Subject is pregnant at time of enrollment in the study. Contraindications to tDCS: metal in the head implanted brain medical devices Clinically significant and unstable medical disorders (e.g., uncontrolled diabetes, uncompensated cardiac issues, heart failure, pulmonary issues, or chronic obstructive pulmonary disease) as self-reported. Clinically significant and unstable psychiatric disorders (e.g., schizophrenia, schizoaffective disorder, other psychosis, bipolar illness, severe depression) as self-reported. Significant visual impairment, as self-reported History of auditory deficiencies, as self-reported History of alcohol or substance abuse within the last 6 months as self-reported Use of carbamazepine within the past 6 months as self-reported. Current use of antidepressants History of neurological disorders as self-reported History of neurosurgery as self-reported

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: Sham tDCS<br>Five consecutive sessions of no tDCS. Each session will last approximately 30 minutes. Current will be applied for 20 minutes. Less than 3 minutes of tDCS has been shown to induce no lasting effects. Normal weight control participants will receive one sham session and one active session. | Device: tDCS<br> <br> * Other names: ActivaDoseII;|
| Experimental: Active tDCS<br>Five consecutive sessions of tDCS administered. Each session will take about 30 minutes. Normal weight control participants will receive one sham session and one active session. | Device: tDCS<br> <br> * Other names: ActivaDoseII;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Amplitude of Eyeblink Startle Responses | Muscle contractions generated by the orbicularis oculi were recorded by a BIOPAC systems bioamplifier (model EMG 100c) passing 10-500 Hz signals, sampling at a rate of 2000/second and amplified by a factor of 5000. Eyeblink startle-responses were measured in response to food and non-food images at two lead-intervals (2500 ms and 6000 ms) to assess emotional responses (e.g., early and late, respectively) for each picture stimulus. Startle responses were assessed during (e.g., while viewing the food, puppy, etc.) and between (e.g., during washout periods; no-images) visual image-processing. Omnibus amplitudes are presented for sham vs active treatment groups for all participants, individuals with obesity and Prader Willi syndrome relative to lean controls. | Amplitude of Eyeblink Startle at Day 30 relative to normal weight controls | 
| Dykens Hyperphagia Questionnaire | The Dykens Hyperphagia Questionnaire is a 13-item instrument that was specifically designed to measure food-related preoccupations and problems, as well as the severity of these concerns. Items on the questionnaire are rated on a five-point scale (1: not a problem to 5: severe and/or frequent problem). Possible scores on the questionnaire range from a minimum score of 0 to a maximum score of 65. Higher scores indicate greater hyperphagia. | Total Score Day 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Three-Factor Eating Questionnaire | The Three-Factor Eating Questionnaire is a self-completed, 51-item questionnaire that measures both cognitive and behavioral aspects of eating (dietary restraint, disinhibition, and hunger), and comprises two parts. Part 1 includes 36 true/false questions, and part 2 includes 14 questions on a four point Likert scale (1= rarely, 2 = sometimes, 3 = usually, 4 = always) and 1 question on a five point Likert scale (1 = eat whatever you want, whenever you want it to 5 = constantly limiting food intake, never 'giving in'; other questions). Higher scores indicate more severe pathology. | Total Scores at Day 30 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obesity, Over weight