Neural Basis of Meal Related Interoceptive Dysfunction in Anorexia Nervosa

Major Depressive Disorder Clinical Trial

Official title:

Neural Basis of Meal Related Interoceptive Dysfunction in Anorexia Nervosa

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02615119
• Other study ID #: 2017-002
• Status: Completed
• Phase: N/A
• Start date: October 1, 2015
• Est. completion date: June 2023

Study information

• Verified date: November 2023
• Source: Laureate Institute for Brain Research, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 97
• Est. completion date: June 2023
• Est. primary completion date: June 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Anorexia
• Anorexia Nervosa
• Anxiety Disorders
• Brain Injuries
• Brain Injury
• Depressive Disorder
• Depressive Disorder, Major
• Generalized Anxiety Disorder
• Major Depressive Disorder
• Panic Disorder

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	Laureate Institute for Brain Research	Tulsa	Oklahoma

Sponsors (2)

Lead Sponsor	Collaborator
Laureate Institute for Brain Research, Inc.	National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Resting cardiac interoceptive sensitivity (heartbeat tapping task tap latencies (in milliseconds))	subject taps with their finger their own perceived heart beat	Baseline
Other	Systolic and diastolic blood pressure (millimeters of mercury; mmHg) during the autonomic task of the valsalva maneuver	blood pressure assessed	Baseline
Other	Systolic and diastolic blood pressure (millimeters of mercury; mmHg) during the autonomic handgrip task.	blood pressure assessed	Baseline
Other	Systolic and diastolic blood pressure (millimeters of mercury; mmHg) during the autonomic task of mental arithmetic.	blood pressure assessed	Baseline
Other	Systolic and diastolic blood pressure (millimeters of mercury; mmHg) during the autonomic cold pressor task.	blood pressure assessed	Baseline
Other	Systolic and diastolic blood pressure (millimeters of mercury; mmHg) during the autonomic task of breath holding).	blood pressure assessed	Baseline
Other	Structural magnetic resonance imaging (cortical thickness in millimeters cubed).	Structural MRI measure: cortical thickness.	Baseline
Other	Functional magnetic resonance imaging (Blood Oxygenation Level Dependent i.e. BOLD signal)	Functional MRI measure: task based activation change	Baseline
Other	EEG (coherence in alpha, beta, theta, delta, gamma frequencies, in Hertz (Hz))	EEG: global and local coherence.	Baseline
Other	Change in heart rate	Average heart rate change versus pre-infusion baseline	Baseline
Other	Change in breathing pattern	Average respiratory volume variability change versus pre-infusion baseline	Baseline
Primary	Change in cardiorespiratory sensation intensity	Visual analogue rating of intensity of heartbeat and breathing sensations (scale: 0 to 10) through study completion (e.g., the day of testing).	Baseline
Secondary	Change in anxiety level	Visual analog rating of level of anxiety (scale: 0 to 10) through study completion, an average of 2 weeks.	Baseline
Secondary	Generalized anxiety disorder severity (Generalized Anxiety Disorder 7 scale)	7 questions on anxiety symptoms	Baseline
Secondary	Panic disorder severity (Panic Disorder Severity scale)	panic symptoms questionnaire	Baseline
Secondary	Major depressive disorder severity (Patient Health Questionnaire-9 scale)	9 questions on depression symptoms	Baseline
Secondary	Eating disorder severity (Eating Disorder Examination scale)	questionnaire about eating disorder symptoms	Baseline