Neural Basis of Meal Related Interoceptive Dysfunction in Anorexia Nervosa

Sponsor

Laureate Institute for Brain Research, Inc. (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT02615119

Collaborator

National Institute of Mental Health (NIMH) (NIH)

302

Enrollment

Location

Arms

146

Duration (Months)

2.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Anorexia Nervosa Major Depressive Disorder Generalized Anxiety Disorder Panic Disorder Brain Injury	Drug: Isoproterenol Drug: Normal saline	N/A

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 Design

Study Type:

Interventional

Actual Enrollment :

302 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Basic Science

Official Title:

Neural Basis of Meal Related Interoceptive Dysfunction in Anorexia Nervosa

Study Start Date :

Oct 1, 2015

Anticipated Primary Completion Date :

Oct 1, 2022

Anticipated Study Completion Date :

Dec 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Anorexia nervosa Intravenous bolus infusions of isoproterenol (up to 4 micrograms per infusion) and normal saline.	Drug: Isoproterenol Intravenous infusions of isoproterenol, delivered in a randomized double blinded order, in each participant from each group. Participants will rate the experience of heartbeat and breathing sensations as well as anxiety induced by the infusion. Other Names: Isuprel Drug: Normal saline Intravenous infusions of normal saline, delivered in a randomized double blinded order, in each participant from each group. Participants will rate the experience of heartbeat and breathing sensations as well as anxiety induced by the infusion. Other Names: Saline
Experimental: Generalized anxiety disorder Intravenous bolus infusions of isoproterenol (up to 4 micrograms per infusion) and normal saline.	Drug: Isoproterenol Intravenous infusions of isoproterenol, delivered in a randomized double blinded order, in each participant from each group. Participants will rate the experience of heartbeat and breathing sensations as well as anxiety induced by the infusion. Other Names: Isuprel Drug: Normal saline Intravenous infusions of normal saline, delivered in a randomized double blinded order, in each participant from each group. Participants will rate the experience of heartbeat and breathing sensations as well as anxiety induced by the infusion. Other Names: Saline
Experimental: Panic disorder Intravenous bolus infusions of isoproterenol (up to 4 micrograms per infusion) and normal saline.	Drug: Isoproterenol Intravenous infusions of isoproterenol, delivered in a randomized double blinded order, in each participant from each group. Participants will rate the experience of heartbeat and breathing sensations as well as anxiety induced by the infusion. Other Names: Isuprel Drug: Normal saline Intravenous infusions of normal saline, delivered in a randomized double blinded order, in each participant from each group. Participants will rate the experience of heartbeat and breathing sensations as well as anxiety induced by the infusion. Other Names: Saline
Experimental: Major depressive disorder Intravenous bolus infusions of isoproterenol (up to 4 micrograms per infusion) and normal saline.	Drug: Isoproterenol Intravenous infusions of isoproterenol, delivered in a randomized double blinded order, in each participant from each group. Participants will rate the experience of heartbeat and breathing sensations as well as anxiety induced by the infusion. Other Names: Isuprel Drug: Normal saline Intravenous infusions of normal saline, delivered in a randomized double blinded order, in each participant from each group. Participants will rate the experience of heartbeat and breathing sensations as well as anxiety induced by the infusion. Other Names: Saline
Experimental: Brain injury Intravenous bolus infusions of isoproterenol (up to 4 micrograms per infusion) and normal saline.	Drug: Isoproterenol Intravenous infusions of isoproterenol, delivered in a randomized double blinded order, in each participant from each group. Participants will rate the experience of heartbeat and breathing sensations as well as anxiety induced by the infusion. Other Names: Isuprel Drug: Normal saline Intravenous infusions of normal saline, delivered in a randomized double blinded order, in each participant from each group. Participants will rate the experience of heartbeat and breathing sensations as well as anxiety induced by the infusion. Other Names: Saline
Active Comparator: Healthy comparison Intravenous bolus infusions of isoproterenol (up to 4 micrograms per infusion) and normal saline.	Drug: Isoproterenol Intravenous infusions of isoproterenol, delivered in a randomized double blinded order, in each participant from each group. Participants will rate the experience of heartbeat and breathing sensations as well as anxiety induced by the infusion. Other Names: Isuprel Drug: Normal saline Intravenous infusions of normal saline, delivered in a randomized double blinded order, in each participant from each group. Participants will rate the experience of heartbeat and breathing sensations as well as anxiety induced by the infusion. Other Names: Saline

Outcome Measures

Primary Outcome Measures

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

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
Major depressive disorder severity (Patient Health Questionnaire-9 scale) [Baseline]
9 questions on depression symptoms
Eating disorder severity (Eating Disorder Examination scale) [Baseline]
questionnaire about eating disorder symptoms

Other Outcome Measures

Resting cardiac interoceptive sensitivity (heartbeat tapping task tap latencies (in milliseconds)) [Baseline]
subject taps with their finger their own perceived heart beat
Systolic and diastolic blood pressure (millimeters of mercury; mmHg) during the autonomic task of the valsalva maneuver [Baseline]
blood pressure assessed
Systolic and diastolic blood pressure (millimeters of mercury; mmHg) during the autonomic handgrip task. [Baseline]
blood pressure assessed
Systolic and diastolic blood pressure (millimeters of mercury; mmHg) during the autonomic task of mental arithmetic. [Baseline]
blood pressure assessed
Systolic and diastolic blood pressure (millimeters of mercury; mmHg) during the autonomic cold pressor task. [Baseline]
blood pressure assessed
Systolic and diastolic blood pressure (millimeters of mercury; mmHg) during the autonomic task of breath holding). [Baseline]
blood pressure assessed
Structural magnetic resonance imaging (cortical thickness in millimeters cubed). [Baseline]
Structural MRI measure: cortical thickness.
Functional magnetic resonance imaging (Blood Oxygenation Level Dependent i.e. BOLD signal) [Baseline]
Functional MRI measure: task based activation change
EEG (coherence in alpha, beta, theta, delta, gamma frequencies, in Hertz (Hz)) [Baseline]
EEG: global and local coherence.
Change in heart rate [Baseline]
Average heart rate change versus pre-infusion baseline
Change in breathing pattern [Baseline]
Average respiratory volume variability change versus pre-infusion baseline

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.

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.