Neural Basis of Meal Related Interoceptive Dysfunction in Anorexia Nervosa

NCT02615119 | Completed DMC

• 1 other identifier: 2017-002
• Study Type: interventional
• Target: 97
• Locations: 1 country
• Sites: 1

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.

Conditions

Anorexia Nervosa; Major Depressive Disorder; Generalized Anxiety Disorder; Panic Disorder; Brain Injury

Keywords

heartbeat; respiration; interoception; anxiety; eating

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Change in anxiety level

  Baseline

• Generalized anxiety disorder severity (Generalized Anxiety Disorder 7 scale)

  Baseline

• Panic disorder severity (Panic Disorder Severity scale)

  Baseline

• Major depressive disorder severity (Patient Health Questionnaire-9 scale)

  Baseline

• Eating disorder severity (Eating Disorder Examination scale)

  Baseline

Other Outcomes (11)

• Resting cardiac interoceptive sensitivity (heartbeat tapping task tap latencies (in milliseconds))

  Baseline

• Systolic and diastolic blood pressure (millimeters of mercury; mmHg) during the autonomic task of the valsalva maneuver

  Baseline

• Systolic and diastolic blood pressure (millimeters of mercury; mmHg) during the autonomic handgrip task.

  Baseline

Study Arms (6)

Anorexia nervosa

EXPERIMENTAL

Intravenous bolus infusions of isoproterenol (up to 4 micrograms per infusion) and normal saline.

Drug: Isoproterenol; Drug: Normal saline

Generalized anxiety disorder

EXPERIMENTAL

Intravenous bolus infusions of isoproterenol (up to 4 micrograms per infusion) and normal saline.

Drug: Isoproterenol; Drug: Normal saline

Panic disorder

EXPERIMENTAL

Intravenous bolus infusions of isoproterenol (up to 4 micrograms per infusion) and normal saline.

Drug: Isoproterenol; Drug: Normal saline

Major depressive disorder

EXPERIMENTAL

Intravenous bolus infusions of isoproterenol (up to 4 micrograms per infusion) and normal saline.

Drug: Isoproterenol; Drug: Normal saline

Brain injury

EXPERIMENTAL

Intravenous bolus infusions of isoproterenol (up to 4 micrograms per infusion) and normal saline.

Drug: Isoproterenol; Drug: Normal saline

Healthy comparison

ACTIVE COMPARATOR

Intravenous bolus infusions of isoproterenol (up to 4 micrograms per infusion) and normal saline.

Drug: Isoproterenol; Drug: Normal saline

Interventions

Isoproterenol DRUG

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.

Also known as: Isuprel

Anorexia nervosa; Brain injury; Generalized anxiety disorder; Healthy comparison; Major depressive disorder; Panic disorder

Normal saline DRUG

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.

Also known as: Saline

Anorexia nervosa; Brain injury; Generalized anxiety disorder; Healthy comparison; Major depressive disorder; Panic disorder

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Laureate Institute for Brain Research, Inc.: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

Laureate Institute for Brain Research

Tulsa, Oklahoma, 74136, United States

Location

Related Publications (1)

• Teed AR, Feinstein JS, Puhl M, Lapidus RC, Upshaw V, Kuplicki RT, Bodurka J, Ajijola OA, Kaye WH, Thompson WK, Paulus MP, Khalsa SS. Association of Generalized Anxiety Disorder With Autonomic Hypersensitivity and Blunted Ventromedial Prefrontal Cortex Activity During Peripheral Adrenergic Stimulation: A Randomized Clinical Trial. JAMA Psychiatry. 2022 Apr 1;79(4):323-332. doi: 10.1001/jamapsychiatry.2021.4225.

  PMID: 35107563 DERIVED

MeSH Terms

Conditions

Anorexia Nervosa; Depressive Disorder, Major; Generalized Anxiety Disorder; Panic Disorder; Brain Injuries; Respiratory Aspiration; Anxiety Disorders

Interventions

Isoproterenol; Saline Solution; Sodium Chloride

Condition Hierarchy (Ancestors)

Feeding and Eating Disorders; Mental Disorders; Depressive Disorder; Mood Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Respiration Disorders; Respiratory Tract Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Catecholamines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Sahib S Khalsa, MD, PhD

  Laureate Institute for Brain Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2015
• First Posted: November 26, 2015
• Study Start: October 1, 2015
• Primary Completion: June 1, 2023
• Study Completion: June 1, 2023
• Last Updated: November 18, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)