Gastrointestinal Interoception in Anorexia Nervosa

Study Overview
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Brief Summary
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Anorexia nervosa (AN) has among the highest mortality rate of any psychiatric illness, yet we have a poor understanding of the biological causes of this disorder. In this study, we use a novel mechanosensory intervention to examine the basic question of whether individuals with AN have abnormal gut sensations and whether such indicators are associated with adverse consequences from the disorder.

Official Title
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A Neurocomputational Assay of Gastrointestinal Interoception in Anorexia Nervosa

Conditions
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Anorexia Nervosa

Intervention / Treatment
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* Device: Vibrant capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HC Inclusion criteria: i. Body mass index ≥ 18.5. ii. Females, ages 15 to 40 years iii. Women of childbearing age: a hormonal (i.e., oral, implantable, or injectable) and single-barrier method, or a double-barrier method of birth control must be used throughout the study. iv. Independently ambulatory v. Possession of a smartphone with data plan vi. English proficiency vii. Willingness and ability to participate in study procedures viii. Provision of signed and dated informed consent form AN Inclusion criteria: i. Primary clinical diagnosis of anorexia nervosa as defined by Laureate Eating Disorders Program ii. Body mass index ≥ 18.5. iii. Transitioned from acute clinical status rating to residential clinical status or partial/intensive outpatient clinical status rating iv. No new medication prescription in the week prior to study randomization, Must be on a stable dose of medication for at least 1 week. v. Females, ages 15 to 40 years vi. Women of childbearing age: a hormonal (i.e., oral, implantable, or injectable) and single-barrier method, or a double-barrier method of birth control must be used throughout the study. vii. Independently ambulatory viii. Possession of a smartphone with data plan ix. English proficiency x. Willingness and ability to participate in study procedures xi. Provision of signed and dated informed consent form Exclusion Criteria: HC Exclusion criteria: i. Current diagnosis of a psychiatric disorder per the MINI International Diagnostic Interview ii. Taking any psychotropic medication iii. Active suicidal ideation with intent or plan iv. Active cutting or skin lacerating behaviors v. Active purging behaviors (specifically, self-induced vomiting), and/or a history of severe self-induced vomiting vi. Pregnancy as defined by a urine screen during screening, and confirmed during each stimulation visit, and must not be lactating vii. History of significant gastrointestinal disorder, including any form of inflammatory bowel disease or gastrointestinal malignancy (celiac disease is accepted if the subject has been treated and is in remission) viii. History of complicated/obstructive diverticular disease ix. Clinical evidence of significant gastroparesis x. Diagnosis of mega-rectum or colon, congenital anorectal malformation, or clinically significant rectocele or rectal prolapse xi. History of intestinal or colonic obstruction, or suspected intestinal obstruction xii. History of intestinal resection (with an exception for appendectomy, cholecystectomy and inguinal hernia repair), history of bariatric surgery or evidence of any structural abnormality of the gastrointestinal tract that might affect transit xiii. History of Zenker's diverticulum, dysphagia, Barrett's esophagus, esophageal stricture or achalasia, transesophageal fistula, or eosinophilic esophagitis. xiv. Clinical evidence (as judged by the investigator) of respiratory, cardiovascular, renal, hepatic, biliary, endocrine, or neurologic disease xv. Chronic use of non-steroidal anti-inflammatory drugs (NSAIDs): chronic use is defined as taking full dose NSAIDs more than three times a week for at least six months. Subjects on cardiac doses of aspirin may be enrolled in the study xvi. Cardiac pacemaker, implantable cardioverter defibrillator, implantable infusion device, or gastric electrical stimulator xxv. Orthostatic hypotension (defined as a drop of ≥ 20 mm Hg in systolic BP or a drop of ≥ 10 mm Hg in diastolic BP when measured shortly after transitioning from lying down to standing) xxvi. Any other condition which in the opinion of the investigator may adversely affect the safety of the subject or would limit the subject's ability to complete the study xxvii. No smartphone/computer or limited access to a smartphone/computer xxviii. Regular use of any of the following medications or procedures: Medications that may substantially affect intestinal motility, prokinetics at high doses (metoclopramide, erythromycin, senna, prucalopride), anti-Parkinsonian medications, opiates, opioids, calcium-channel blockers, enemas xxix. History of a GI bleed within the last 3 months xxx. Pelvic floor dysfunction/defecatory disorder, based on subject history xxxi. Planning to undergo MRI during study time frame xxxii. Any known allergy to soybean or beeswax or Calcium Carbonate xxxiii. Bradycardia less than 40 beats per minute xxxiv. Pain Disorder AN Exclusion criteria: i. Active suicidal ideation with intent or plan ii. Active cutting or skin lacerating behaviors iii. Active purging behviors (specifically, self-induced vomiting), and/or a history of severe self-induced vomiting iv. Pregnancy as defined by a urine screen during screening, and confirmed during each stimulation visit, and must not be lactating v. History of significant gastrointestinal disorder, including any form of inflammatory bowel disease or gastrointestinal malignancy (celiac disease is accepted if the subject has been treated and is in remission) vi. History of complicated/obstructive diverticular disease vii. Clinical evidence of significant gastroparesis viii. Diagnosis of mega-rectum or colon, congenital anorectal malformation, or clinically significant rectocele or rectal prolapse ix. History of intestinal or colonic obstruction, or suspected intestinal obstruction x. History of intestinal resection (with an exception for appendectomy, cholecystectomy and inguinal hernia repair), history of bariatric surgery or evidence of any structural abnormality of the gastrointestinal tract that might affect transit xi. History of Zenker's diverticulum, dysphagia, Barrett's esophagus, esophageal stricture or achalasia, transesophageal fistula, or eosinophilic esophagitis. xii. Clinical evidence (as judged by the investigator) of respiratory, cardiovascular, renal, hepatic, biliary, endocrine, or neurologic disease xiii. Chronic use of non-steroidal anti-inflammatory drugs (NSAIDs): chronic use is defined as taking full dose NSAIDs more than three times a week for at least six months. Subjects on cardiac doses of aspirin may be enrolled in the study xiv. Cardiac pacemaker, implantable cardioverter defibrillator, implantable infusion device, or gastric electrical stimulator xv. Orthostatic hypotension (defined as a drop of ≥ 20 mm Hg in systolic BP or a drop of ≥ 10 mm Hg in diastolic BP when measured shortly after transitioning from lying down to standing) xvi. Any other condition which in the opinion of the investigator may adversely affect the safety of the subject or would limit the subject's ability to complete the study xvii. No smartphone/computer or limited access to a smartphone/computer xviii. Regular use of any of the following medications or procedures: Medications that may substantially affect intestinal motility, prokinetics at high doses (metoclopramide, erythromycin, senna, prucalopride), anti-Parkinsonian medications, opiates, opioids, calcium-channel blockers, enemas xix. History of GI bleed within the last 3 months xx. Pelvic floor dysfunction/defecatory disorder, based on subject history xxi. Planning to undergo MRI during study time frame xxii. Any known allergy to soybean or beeswax, or Calcium Carbonate xxiii. Bradycardia less than 40 beats per minute xxiv. Pain Disorder

Ages Eligible for Study
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Minimum Age: 15 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Capsule stimulation<br>Participants in this arm will receive gastric stimulation via the Vibrant capsule | Device: Vibrant capsule<br>* A capsule delivering mechanical vibrations<br>|
| Placebo Comparator: Placebo stimulation<br>Participants in this arm will receive no gastric stimulation via a placebo capsule | Device: Vibrant capsule<br>* A capsule delivering mechanical vibrations<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Interoceptive precision | Interoceptive sensory precision | At baseline | 
| Interoceptive prior | Interoceptive prior expectaiton | At baseline | 
| Learning rate | Interoceptive learning rate | At baseline | 
| Evoked response potential | Electroencephalogram (EEG) evoked response amplitude within 700 millisecond period following vibration onset | At baseline | 
| Electrogastrogram | Stomach electrogastrogram (EGG) power in bradygastria, normogastria, tachygastria and total power bands | At baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Normalized A prime | Signal detection accuracy measure | At baseline | 
| Illness status | Relapse, remission, or recovery status | At 1 month, 3 month, and 6 month follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Interoception