Neural Basis of Meal Related Interoceptive Dysfunction in Anorexia Nervosa

November 16, 2023 updated by: Laureate Institute for Brain Research, Inc.
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

97

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Oklahoma
      • Tulsa, Oklahoma, United States, 74136
        • Laureate Institute for Brain Research

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

Yes

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in cardiorespiratory sensation intensity
Time Frame: Baseline
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 Outcome Measures

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

Other Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Laureate Institute for Brain Research, Inc.

Collaborators

National Institute of Mental Health (NIMH)

Investigators

  • Principal Investigator: Sahib S Khalsa, MD, PhD, Laureate Institute for Brain Research

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 1, 2015

Primary Completion (Actual)

June 1, 2023

Study Completion (Actual)

June 1, 2023

Study Registration Dates

First Submitted

November 18, 2015

First Submitted That Met QC Criteria

November 23, 2015

First Posted (Estimated)

November 26, 2015

Study Record Updates

Last Update Posted (Estimated)

November 20, 2023

Last Update Submitted That Met QC Criteria

November 16, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2017-002

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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