Neural Basis of Meal Related Interoceptive Dysfunction in Anorexia Nervosa

Not Applicable

Completed

• Conditions: Panic Disorder; Major Depressive Disorder; Brain Injury; Anorexia Nervosa; Generalized Anxiety Disorder
• Interventions: Drug: Isoproterenol; Drug: Normal saline

• Registration Number: NCT02615119
• Lead Sponsor: Laureate Institute for Brain Research, Inc.

Brief Summary

This study aims to identify the brain regions responsible for encoding cardiorespiratory 'interoceptive' sensations and determine whether they are dysfunctional in individuals affected by eating disorders, anxiety, depression, or brain injury. By evaluating the same interoceptive sensations across different human illnesses, the investigators hope to provide convergent evidence resulting in identification of core underlying neural processes, and to discern relative contributions in each condition.

Detailed Description

The human brain has constant access to a multitude of complex signals, which it must simplify and organize in order to sustain the integrity of the organism. Many of these signals originate from outside of the body, such as lights, sounds, and smells, and much is known about how humans consciously perceive these 'exteroceptive' signals and how the human brain represents them. Comparatively little is known about how the human brain processes 'interoceptive' signals originating from inside of the body, despite the fact that the brain has access to far more of them (for instance, intestinal tension, bladder distension, breath, heartbeat, body temperature, blood pressure, serum osmolality, inflammation, proprioception etc.).

The current study study therefore aims to identify the brain regions responsible for encoding cardiorespiratory 'interoceptive' sensations and determine whether they are dysfunctional in individuals affected by eating disorders, anxiety, depression, or brain injury. Participants in this study will receive stimulation of the cardiorespiratory channel of the interoceptive system using bolus intravenous infusions of isoproterenol, a peripherally acting medication similar to adrenaline, and saline. Stimulation will occur during functional magnetic resonance imaging (fMRI) as well as outside of the fMRI scanner. After the scan participants will consume a meal. By evaluating the same interoceptive sensations across different human illnesses, the investigators hope to provide convergent evidence resulting in identification of core underlying neural processes, and to discern relative contributions in each condition.

Study Timeline

• Study Start: 2015-10-01
• Study First Submitted: 2015-11-18
• Study First Submitted QC: 2015-11-23
• Study First Posted: 2015-11-26
• Primary Completion: 2023-06
• Study Completion: 2023-06
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-16
• Last Update Posted: 2023-11-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 97

Inclusion Criteria

• Diagnostic and Statistical Manual 5 (DSM 5) criteria for anorexia nervosa and age 18 to 40, or generalized anxiety disorder, or panic disorder, or major depressive disorder, or brain injury caused either by herpes simplex encephalitis or Urbach-Wiethe disease.

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Exclusion Criteria

• DSM 5 diagnosis with any of the following: Schizophrenia spectrum and other psychotic disorders, bipolar and related disorders, antisocial personality disorder, active suicidal ideation with intent or plan
• Current cardiac arrhythmia
• Current respiratory disease
• Seizure disorder
• MRI contraindications including: cardiac pacemaker, metal fragments in eyes/skin/body (shrapnel), aortic/aneurysm clips, prosthesis, by-pass surgery/coronary artery clips, hearing aid, heart valve replacement, shunt (ventricular or spinal), electrodes, metal plates/pins/screws/ wires, or neuro/bio-stimulators (TENS unit), persons who have ever been a professional metal worker/welder, history of eye surgery/eyes washed out because of metal, vision problems uncorrectable with lenses, inability to lie still on one's back for 60-120 minutes; prior neurosurgery; tattoos or cosmetic makeup with metal dyes, unwillingness to remove body piercings, and pregnancy.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Panic disorder	Normal saline	Intravenous bolus infusions of isoproterenol (up to 4 micrograms per infusion) and normal saline.
Major depressive disorder	Normal saline	Intravenous bolus infusions of isoproterenol (up to 4 micrograms per infusion) and normal saline.
Anorexia nervosa	Normal saline	Intravenous bolus infusions of isoproterenol (up to 4 micrograms per infusion) and normal saline.
Healthy comparison	Normal saline	Intravenous bolus infusions of isoproterenol (up to 4 micrograms per infusion) and normal saline.
Generalized anxiety disorder	Normal saline	Intravenous bolus infusions of isoproterenol (up to 4 micrograms per infusion) and normal saline.
Brain injury	Normal saline	Intravenous bolus infusions of isoproterenol (up to 4 micrograms per infusion) and normal saline.
Anorexia nervosa	Isoproterenol	Intravenous bolus infusions of isoproterenol (up to 4 micrograms per infusion) and normal saline.
Healthy comparison	Isoproterenol	Intravenous bolus infusions of isoproterenol (up to 4 micrograms per infusion) and normal saline.
Generalized anxiety disorder	Isoproterenol	Intravenous bolus infusions of isoproterenol (up to 4 micrograms per infusion) and normal saline.
Panic disorder	Isoproterenol	Intravenous bolus infusions of isoproterenol (up to 4 micrograms per infusion) and normal saline.
Major depressive disorder	Isoproterenol	Intravenous bolus infusions of isoproterenol (up to 4 micrograms per infusion) and normal saline.
Brain injury	Isoproterenol	Intravenous bolus infusions of isoproterenol (up to 4 micrograms per infusion) and normal saline.

Primary Outcome Measures

Name	Time	Method
Change in cardiorespiratory sensation intensity	Baseline	Visual analogue rating of intensity of heartbeat and breathing sensations (scale: 0 to 10) through study completion (e.g., the day of testing).

Secondary Outcome Measures

Name	Time	Method
Eating disorder severity (Eating Disorder Examination scale)	Baseline	questionnaire about eating disorder symptoms
Major depressive disorder severity (Patient Health Questionnaire-9 scale)	Baseline	9 questions on depression symptoms
Change in anxiety level	Baseline	Visual analog rating of level of anxiety (scale: 0 to 10) through study completion, an average of 2 weeks.
Generalized anxiety disorder severity (Generalized Anxiety Disorder 7 scale)	Baseline	7 questions on anxiety symptoms
Panic disorder severity (Panic Disorder Severity scale)	Baseline	panic symptoms questionnaire

Trial Locations

Locations (1)

Laureate Institute for Brain Research; 🇺🇸 Tulsa, Oklahoma, United States