Hyperphagia, Prader-Willi Syndrome
Conditions
Keywords
Obesity, Over weight
Brief summary
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
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.
Interventions
DEVICEtDCS
Sponsors
Prader-Willi Syndrome Association USA
Harvard Medical School (HMS and HSDM)
Foundation for Prader-Willi Research
University of Kansas Medical Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
Yes
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: 1. metal in the head 2. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Amplitude of Eyeblink Startle Responses | Amplitude of Eyeblink Startle at Day 30 relative to normal weight controls | 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. |
| Dykens Hyperphagia Questionnaire | Total Score Day 30 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Three-Factor Eating Questionnaire | Total Scores at Day 30 | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sham tDCS 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.
tDCS | 12 |
| Active tDCS 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.
tDCS | 19 |
| Total | 31 |
Baseline characteristics
| Characteristic | Active tDCS | Total | Sham tDCS |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 19 Participants | 31 Participants | 12 Participants |
| Age, Continuous all patients | 39.3 years STANDARD_DEVIATION 13.6 | 35.8 years STANDARD_DEVIATION 13.7 | 33.2 years STANDARD_DEVIATION 13.7 |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment United States | 19 Participants | 31 Participants | 12 Participants |
| Sex: Female, Male Female | 7 Participants | 14 Participants | 7 Participants |
| Sex: Female, Male Male | 12 Participants | 17 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 19 |
| other Total, other adverse events | 0 / 12 | 0 / 19 |
| serious Total, serious adverse events | 0 / 12 | 0 / 19 |
Outcome results
Primary
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.
Time frame: Amplitude of Eyeblink Startle at Day 30 relative to normal weight controls
Population: All participants
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sham tDCS | Amplitude of Eyeblink Startle Responses | All Participants | 0.006 microvolts | Standard Error 0.001 |
| Sham tDCS | Amplitude of Eyeblink Startle Responses | Obese Participants | 0.008 microvolts | Standard Error 0.002 |
| Sham tDCS | Amplitude of Eyeblink Startle Responses | Participants with PWS | 0.004 microvolts | Standard Error 0.002 |
| Active tDCS | Amplitude of Eyeblink Startle Responses | All Participants | 0.001 microvolts | Standard Error 0.001 |
| Active tDCS | Amplitude of Eyeblink Startle Responses | Obese Participants | 0.001 microvolts | Standard Error 0.001 |
| Active tDCS | Amplitude of Eyeblink Startle Responses | Participants with PWS | 0.001 microvolts | Standard Error 0.001 |
Primary
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.
Time frame: Total Score Day 30
Population: all participants
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sham tDCS | Dykens Hyperphagia Questionnaire | Normal Weight Participants | 19.8 score on a scale | Standard Deviation 4 |
| Sham tDCS | Dykens Hyperphagia Questionnaire | Obese Participants | 15.3 score on a scale | Standard Deviation 5.1 |
| Sham tDCS | Dykens Hyperphagia Questionnaire | Participants with PWS | 28.3 score on a scale | Standard Deviation 6.1 |
| Active tDCS | Dykens Hyperphagia Questionnaire | Normal Weight Participants | 22.1 score on a scale | Standard Deviation 6.7 |
| Active tDCS | Dykens Hyperphagia Questionnaire | Obese Participants | 24.8 score on a scale | Standard Deviation 5.1 |
| Active tDCS | Dykens Hyperphagia Questionnaire | Participants with PWS | 25.3 score on a scale | Standard Deviation 6 |
Secondary
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.
Time frame: Total Scores at Day 30
Population: All participants
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sham tDCS | Three-Factor Eating Questionnaire | Normal Weight Participants | 19.82 score on a scale | Standard Deviation 9.1 |
| Sham tDCS | Three-Factor Eating Questionnaire | Obese Participants | 16.3 score on a scale | Standard Deviation 8 |
| Sham tDCS | Three-Factor Eating Questionnaire | Participants with PWS | 32.7 score on a scale | Standard Deviation 5.9 |
| Active tDCS | Three-Factor Eating Questionnaire | Participants with PWS | 27.8 score on a scale | Standard Deviation 5 |
| Active tDCS | Three-Factor Eating Questionnaire | Normal Weight Participants | 20.5 score on a scale | Standard Deviation 10.3 |
| Active tDCS | Three-Factor Eating Questionnaire | Obese Participants | 25.1 score on a scale | Standard Deviation 10.7 |