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Neural Basis of Meal Related Interoceptive Dysfunction in Anorexia Nervosa

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ClinicalTrials.gov Identifier: NCT02615119
Recruitment Status : Recruiting
First Posted : November 26, 2015
Last Update Posted : August 20, 2019
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Anorexia Nervosa Major Depressive Disorder Generalized Anxiety Disorder Panic Disorder Brain Injury Drug: Isoproterenol Drug: Normal saline Not Applicable

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 310 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 : October 2015
Estimated Primary Completion Date : October 2020
Estimated Study Completion Date : December 2027

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Anxiety

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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: Saline




Primary Outcome Measures :
  1. 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).


Secondary Outcome Measures :
  1. 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.

  2. Generalized anxiety disorder severity (Generalized Anxiety Disorder 7 scale) [ Time Frame: Baseline ]
    7 questions on anxiety symptoms

  3. Panic disorder severity (Panic Disorder Severity scale) [ Time Frame: Baseline ]
    panic symptoms questionnaire

  4. Major depressive disorder severity (Patient Health Questionnaire-9 scale) [ Time Frame: Baseline ]
    9 questions on depression symptoms

  5. Eating disorder severity (Eating Disorder Examination scale) [ Time Frame: Baseline ]
    questionnaire about eating disorder symptoms


Other Outcome Measures:
  1. Resting cardiac interoceptive sensitivity (heartbeat tapping task tap latencies (in milliseconds)) [ Time Frame: Baseline ]
    subject taps with their finger their own perceived heart beat

  2. Systolic and diastolic blood pressure (millimeters of mercury; mmHg) during the autonomic task of the valsalva maneuver [ Time Frame: Baseline ]
    blood pressure assessed

  3. Systolic and diastolic blood pressure (millimeters of mercury; mmHg) during the autonomic handgrip task. [ Time Frame: Baseline ]
    blood pressure assessed

  4. Systolic and diastolic blood pressure (millimeters of mercury; mmHg) during the autonomic task of mental arithmetic. [ Time Frame: Baseline ]
    blood pressure assessed

  5. Systolic and diastolic blood pressure (millimeters of mercury; mmHg) during the autonomic cold pressor task. [ Time Frame: Baseline ]
    blood pressure assessed

  6. Systolic and diastolic blood pressure (millimeters of mercury; mmHg) during the autonomic task of breath holding). [ Time Frame: Baseline ]
    blood pressure assessed

  7. Structural magnetic resonance imaging (cortical thickness in millimeters cubed). [ Time Frame: Baseline ]
    Structural MRI measure: cortical thickness.

  8. Functional magnetic resonance imaging (cerebral blood flow, in ml/100g/min) [ Time Frame: Baseline ]
    Functional MRI measure: resting state functional connectivity.

  9. EEG (coherence in alpha, beta, theta, delta, gamma frequencies, in Hertz (Hz)) [ Time Frame: Baseline ]
    EEG: global and local coherence.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02615119


Contacts
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Contact: Valerie Upshaw, RN 9185025176 vupshaw@laureateinstitute.org

Locations
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United States, Oklahoma
Laureate Institute for Brain Research Recruiting
Tulsa, Oklahoma, United States, 74136
Sponsors and Collaborators
Laureate Institute for Brain Research, Inc.
National Institute of Mental Health (NIMH)
Investigators
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Principal Investigator: Sahib S Khalsa, MD, PhD Laureate Institute for Brain Research

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Responsible Party: Laureate Institute for Brain Research, Inc.
ClinicalTrials.gov Identifier: NCT02615119     History of Changes
Other Study ID Numbers: 2017-002
First Posted: November 26, 2015    Key Record Dates
Last Update Posted: August 20, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Laureate Institute for Brain Research, Inc.:
heartbeat
respiration
interoception
anxiety
eating
Additional relevant MeSH terms:
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Brain Injuries
Disease
Anorexia
Depressive Disorder
Depressive Disorder, Major
Anxiety Disorders
Anorexia Nervosa
Panic Disorder
Pathologic Processes
Mood Disorders
Mental Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Wounds and Injuries
Signs and Symptoms, Digestive
Signs and Symptoms
Feeding and Eating Disorders
Isoproterenol
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents