Anorexia NervosaNCT02615119
Neural Basis of Meal Related Interoceptive Dysfunction in Anorexia Nervosa
A study testing Isoproterenol and Normal saline in people with Anorexia Nervosa and Major Depressive Disorder, run by Laureate Institute for Brain Research, Inc. at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Anorexia Nervosa, Major Depressive Disorder, Generalized Anxiety Disorder
- What is being tested?
- Isoproterenol and Normal saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 97 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2015to Jun 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Laureate Institute for Brain Research
Tulsa, Oklahoma, 74136
About this study
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.
Read the 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.
- Conditions
- Anorexia Nervosa, Major Depressive Disorder, Generalized Anxiety Disorder, Panic Disorder, Brain Injury
- Being tested
- Isoproterenol, Normal saline
- Keywords
- heartbeat, respiration, interoception, anxiety, eating
- Medical subject headings
- Anorexia Nervosa, Depressive Disorder, Major, Generalized Anxiety Disorder, Panic Disorder, Brain Injuries, Respiratory Aspiration, Anxiety Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IsoproterenolDrug
Also called Isuprel
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 salineDrug
Also called 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.
| Study group | Role | What they receive |
|---|---|---|
| Anorexia nervosa | Experimental | Intravenous bolus infusions of isoproterenol (up to 4 micrograms per infusion) and normal saline. Receives: Drug: Isoproterenol; Drug: Normal saline |
| Generalized anxiety disorder | Experimental | Intravenous bolus infusions of isoproterenol (up to 4 micrograms per infusion) and normal saline. Receives: Drug: Isoproterenol; Drug: Normal saline |
| Panic disorder | Experimental | Intravenous bolus infusions of isoproterenol (up to 4 micrograms per infusion) and normal saline. Receives: Drug: Isoproterenol; Drug: Normal saline |
| Major depressive disorder | Experimental | Intravenous bolus infusions of isoproterenol (up to 4 micrograms per infusion) and normal saline. Receives: Drug: Isoproterenol; Drug: Normal saline |
| Brain injury | Experimental | Intravenous bolus infusions of isoproterenol (up to 4 micrograms per infusion) and normal saline. Receives: Drug: Isoproterenol; Drug: Normal saline |
| Healthy comparison | Active comparator | Intravenous bolus infusions of isoproterenol (up to 4 micrograms per infusion) and normal saline. Receives: Drug: Isoproterenol; Drug: Normal saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Baseline
Secondary outcomes (5)
Change in anxiety level
Visual analog rating of level of anxiety (scale: 0 to 10) through study completion, an average of 2 weeks.
Measured: Baseline
Generalized anxiety disorder severity (Generalized Anxiety Disorder 7 scale)
7 questions on anxiety symptoms
Measured: Baseline
Panic disorder severity (Panic Disorder Severity scale)
panic symptoms questionnaire
Measured: Baseline
Major depressive disorder severity (Patient Health Questionnaire-9 scale)
9 questions on depression symptoms
Measured: Baseline
Eating disorder severity (Eating Disorder Examination scale)
questionnaire about eating disorder symptoms
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Nov 2015 (estimated)
- Study start1 Oct 2015
- Primary completionJun 2023
- Study completionJun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Anorexia NervosaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 97 participants (actual)
Sponsor and investigators
- Lead sponsor
- Laureate Institute for Brain Research, Inc.
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor
- Investigators
- Sahib S Khalsa, MD, PhD, Principal investigator, Laureate Institute for Brain Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02615119
- Sponsor's protocol ID
- 2017-002
- Status last verified
- Nov 2023
- First submitted
- 18 Nov 2015
- Last updated
- 18 Nov 2023
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 35107563
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neural Basis of Meal Related Interoceptive Dysfunction in Anorexia Nervosa
- ClinicalTrials.gov ID
- NCT02615119
- Acronym / sponsor ID
- 2017-002
- Conditions
- Anorexia Nervosa, Major Depressive Disorder, Generalized Anxiety Disorder, Panic Disorder, Brain Injury
- Keywords
- heartbeat, respiration, interoception, anxiety, eating
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 97 participants (actual)
- Lead sponsor
- Laureate Institute for Brain Research, Inc.University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 1 Oct 2015 (actual)
- Primary completion
- Jun 2023 (actual)
- Study completion
- Jun 2023 (actual)
- First posted
- 26 Nov 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Anorexia nervosa | Experimental | Drug: Isoproterenol, Drug: Normal salineIntravenous bolus infusions of isoproterenol (up to 4 micrograms per infusion) and normal saline. |
| Generalized anxiety disorder | Experimental | Drug: Isoproterenol, Drug: Normal salineIntravenous bolus infusions of isoproterenol (up to 4 micrograms per infusion) and normal saline. |
| Panic disorder | Experimental | Drug: Isoproterenol, Drug: Normal salineIntravenous bolus infusions of isoproterenol (up to 4 micrograms per infusion) and normal saline. |
| Major depressive disorder | Experimental | Drug: Isoproterenol, Drug: Normal salineIntravenous bolus infusions of isoproterenol (up to 4 micrograms per infusion) and normal saline. |
| Brain injury | Experimental | Drug: Isoproterenol, Drug: Normal salineIntravenous bolus infusions of isoproterenol (up to 4 micrograms per infusion) and normal saline. |
| Healthy comparison | Active comparator | Drug: Isoproterenol, Drug: Normal salineIntravenous bolus infusions of isoproterenol (up to 4 micrograms per infusion) and normal saline. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IsoproterenolAlso: IsuprelIntravenous 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. | Drug | Anorexia nervosa, Brain injury, Generalized anxiety disorder, Healthy comparison, Major depressive disorder, Panic disorder |
| Normal salineAlso: SalineIntravenous 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. | Drug | Anorexia nervosa, Brain injury, Generalized anxiety disorder, Healthy comparison, Major depressive disorder, Panic disorder |
Primary outcome
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).
5 secondary outcomes
Change in anxiety level
Time frame: Baseline
Generalized anxiety disorder severity (Generalized Anxiety Disorder 7 scale)
Time frame: Baseline
Panic disorder severity (Panic Disorder Severity scale)
Time frame: Baseline
Major depressive disorder severity (Patient Health Questionnaire-9 scale)
Time frame: Baseline
Eating disorder severity (Eating Disorder Examination scale)
Time frame: Baseline
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2023.
- Derived from this study: PubMed 35107563Teed 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sahib S Khalsa, MD, PhD principal investigator
Laureate Institute for Brain Research
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Isoproterenol and Normal saline in people with Anorexia Nervosa and Major Depressive Disorder, run by Laureate Institute for Brain Research, Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in cardiorespiratory sensation intensity (time frame: Baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02615119, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2023.