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Dopamine Receptor Contributions to Prediction Error and Reversal Learning in Anorexia Nervosa

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04128683
Recruitment Status : Not yet recruiting
First Posted : October 16, 2019
Last Update Posted : October 18, 2019
Sponsor:
Information provided by (Responsible Party):
Guido Frank, University of California, San Diego

Brief Summary:

Anorexia nervosa (AN) is an eating disorder associated with intense fear of weight gain, food refusal, and severe weight loss. AN has the highest mortality rate among the psychiatric disorders; however, little is known about biomarkers, and no medication has been approved for AN. Many individuals only partially recover, and treatment options, especially for the psychological components of the illness, are not very effective, highlighting the need for more effective treatments.

Brain reward pathways have a direct impact on the drive to eat, and a variety of neuroimaging studies have suggested altered reward processing in AN. The neurotransmitter dopamine has a central role in the reward circuitry to drive food approach, and the dynamic interplay between dopamine receptor response and food restriction could have implications for the pathophysiology of AN. Dopamine-related brain function has been studied indirectly using functional magnetic resonance brain imaging (fMRI) and tasks that deliver reward stimuli unexpectedly, that elicit the so-called prediction error (PE) response.

Research in AN showed repeatedly altered PE processing suggesting altered dopamine circuit function in the disorder.

Dopamine and PE response have also been associated with altered reversal learning, which has important treatment implication for AN as reversal learning is impaired in the disorder and modulation of the dopamine system could improve treatment.


Condition or disease Intervention/treatment Phase
Anorexia Nervosa Drug: amisulpride Drug: bromocriptine Early Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 44 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Other
Official Title: Toward Understanding Dopamine Receptor Contributions to Prediction Error and Reversal Learning in Anorexia Nervosa
Estimated Study Start Date : December 2019
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : December 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Healthy Controls
Healthy Control Subjects
Drug: amisulpride
Dopamine D2 antagonist to test how it affects brain response and behavior to prediction error and reversal tasks during functional magnetic resonance imaging (fMRI).
Other Name: Solian

Drug: bromocriptine
Dopamine D2 receptor agonist test how it affects brain response and behavior to prediction error and reversal tasks during functional magnetic resonance imaging (fMRI).
Other Name: Parlodel

Experimental: Anorexia Nervosa
Anorexia Nervosa Subjects
Drug: amisulpride
Dopamine D2 antagonist to test how it affects brain response and behavior to prediction error and reversal tasks during functional magnetic resonance imaging (fMRI).
Other Name: Solian

Drug: bromocriptine
Dopamine D2 receptor agonist test how it affects brain response and behavior to prediction error and reversal tasks during functional magnetic resonance imaging (fMRI).
Other Name: Parlodel




Primary Outcome Measures :
  1. fMRI brain response within group across the three conditions and distinction between conditions within groups [ Time Frame: Immediate during brain scanning ]
    Study participants will have three study days with either a medication or placebo condition and will undergo fMRI during which they perform prediction error or reversal learning tasks and the effect on brain response and behavior are measured immediately during scanning.


Secondary Outcome Measures :
  1. Difference in brain response between groups [ Time Frame: Immediate during brain scanning ]
    Study participants will have three study days with either a medication or placebo condition and will undergo fMRI during which they perform prediction error or reversal learning tasks and the effect on brain response and behavior are measured immediately during scanning.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 29 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Healthy Controls

  • Females ages 18-29 years
  • Healthy body weight between 90 and 110 % average body weight since puberty.
  • Regular monthly menstrual cycle
  • Edinburgh Handedness Inventory Revised (EHI-R) LQ* score > +200
  • English is primary language spoken

Restricting Type Anorexia Nervosa

  • Females ages 18-29 years
  • Diagnostic criteria. Current diagnosis of AN, including being underweight below 17.5 body mass index (BMI, kg/m2), will have a severe fear of weight gain, body image distortion and absence of the menstrual cycle over three consecutive months.
  • First 1-2 weeks in treatment at The University of California San Diego Eating Disorders Center for Treatment and Research or Rady Children's Hospital San Diego Medical Behavioral Unit.
  • Restricting subtype, that is without binge/purge behaviors
  • Edinburgh Handedness Inventory Revised (EHI-R) LQ* score > +200
  • English is primary language spoken

Exclusion Criteria:

Healthy Controls

  • Current pregnancy or breast feeding within last 3 months
  • Illiterate/Blind individuals
  • First degree relative with current or past eating disorder
  • Current Medications other than BCP or IUD
  • Contraindications to amisulpride or bromocriptine (as determined through medical history in bioscreen and PI interview) including: Syncopal migraine; Uncontrolled hypertension; Pheochromocytoma; Prolactinoma; Breast cancer; hypersensitivity/allergy to amisulpride or bromocriptine; History of long QT syndrome; Family history of sudden death or long QT syndrome; History of seizures or seizure disorder
  • Past or present Axis I psychiatric disorder including substance or alcohol use disorder as determined through SCID-5 clinical interview
  • Major Medical illness (as determined through medical history in bioscreen and PI interview) such as:

    o Conditions that are life threatening: cancer heart disease stroke HIV/AIDS

    o Conditions that are life threatening Conditions that cause serious disability without necessarily being life threatening: stroke closed head or spinal cord injuries mental retardation congenital malformations.

    o Conditions that cause significant pain or discomfort that can cause serious interruptions to life activities: severe allergies migraine arthritis sickle cell disease

    o Conditions that require major commitments of time and effort from care-givers for a substantial period of time: mobility disorders blindness Alzheimer's disease and other dementias chronic obstructive pulmonary disease paraplegia or quadriplegia Down's syndrome depression

    o Conditions that may require frequent monitoring: diabetes conditions requiring anticoagulation treatment severe asthma severe allergies schizophrenia and other psychotic illnesses.

    o Conditions that predict or are associated with severe consequences: hypertension (associated with heart disease) depression (associated with suicide) diabetes (associated with blindness, kidney failure) alcohol and other substance abuse (associated with intentional and unintentional injuries).

  • Recent history of suspected substance abuse or a lifetime history of psychostimulant abuse and/or dependence
  • Metal implants or braces (as determined through fMRI screening form)

Anorexia Nervosa

  • Pregnancy or breast feeding within last 3 months
  • Lifetime history of bipolar disorder or psychosis
  • Illiterate/Blind individuals
  • Contraindications to amisulpride or bromocriptine (as determined through medical history in bioscreen and PI interview) including: Syncopal migraine; Uncontrolled hypertension; Pheochromocytoma; Prolactinoma; Breast cancer; hypersensitivity/allergy to amisulpride or bromocriptine; History of long QT syndrome; Family history of sudden death or long QT syndrome; History of seizures or seizure disorder
  • Use of an anti-psychotic or other dopamine acting medication including stimulants within the past week at time of MRI
  • Recent history of substance abuse or dependence (within the last month)
  • Major Medical illness (as determined through medical history in bioscreen and PI interview) such as:

    o Conditions that are life threatening: cancer heart disease stroke HIV/AIDS

    o Conditions that are life threatening Conditions that cause serious disability without necessarily being life threatening: stroke closed head or spinal cord injuries mental retardation congenital malformations.

    o Conditions that cause significant pain or discomfort that can cause serious interruptions to life activities: severe allergies migraine arthritis sickle cell disease

    o Conditions that require major commitments of time and effort from care-givers for a substantial period of time: mobility disorders blindness Alzheimer's disease and other dementias chronic obstructive pulmonary disease paraplegia or quadriplegia Down's syndrome

    o Conditions that may require frequent monitoring: diabetes conditions requiring anticoagulation treatment severe asthma severe allergies schizophrenia and other psychotic illnesses.

    o Conditions that predict or are associated with severe consequences: hypertension (associated with heart disease) diabetes (associated with blindness, kidney failure) alcohol and other substance abuse (associated with intentional and unintentional injuries) within the last month

  • Metal implants or braces (as determined through fMRI screening form)

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): NCT04128683


Contacts
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Contact: Megan E Shott, BS 858-246-5272 mshott@ucsd.edu

Sponsors and Collaborators
University of California, San Diego
Investigators
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Principal Investigator: Guido Frank, MD University of California, San Diego

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Responsible Party: Guido Frank, Professor, University of California, San Diego
ClinicalTrials.gov Identifier: NCT04128683    
Other Study ID Numbers: 191348
First Posted: October 16, 2019    Key Record Dates
Last Update Posted: October 18, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Anorexia
Anorexia Nervosa
Signs and Symptoms, Digestive
Signs and Symptoms
Feeding and Eating Disorders
Mental Disorders
Dopamine
Bromocriptine
Amisulpride
Cardiotonic Agents
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Protective Agents
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Dopamine Antagonists
Antidepressive Agents, Second-Generation
Antidepressive Agents
Antiparkinson Agents
Anti-Dyskinesia Agents
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Dopamine Agonists