Monoamine Contributions to Neurocircuitry in Eating Disorders

This study will use brain imaging technologies to measure several neurotransmitters (serotonin and dopamine) that contribute to our abilities to respond to reward or inhibit our impulses, and which are known to be altered in the brain of people with anorexia nervosa (AN) and bulimia nervosa (BN). Because palatable food stimulates dopamine secretion, we propose to use a challenge with brain imaging that will stimulate dopamine release which we hypothesize will generate anxiety rather than pleasure in AN, and will help explain why AN restrict eating in order to reduce anxiety. This study will help to understand the unique puzzling symptoms in eating disorders and contribute to finding better methods for identifying effective treatments for these often relapsing and sometimes chronic disorders.

Study Overview

• Status: Completed
• Conditions: Eating Disorder
• Intervention / Treatment: Drug: [11C]raclopride; Drug: [11C]DASB; Drug: amphetamine

Detailed Description

Alterations of serotonin (5-HT) and dopamine (DA) activity may contribute to extremes of appetitive behaviours in anorexia nervosa (AN) and bulimia nervosa (BN), through effects on inhibitory and reward neural pathways. To avoid the confounding effects of malnutrition, and because they have behaviours and neural circuit alterations relevant for this study, we will study 25 recovered (REC) restricting-type AN, 25 REC bulimic-type AN (AN-BN), 25 REC BN, and 25 control women (CW). This 5 year study, of women 18 to 45 years old, will employ positron emission tomography (PET) imaging with radioligands for the 5-HT transporter ([11C]DASB) and DA D2/D3 receptors ([11C]raclopride).

• Study Type: Interventional
• Enrollment (Actual): 88
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92102
      • University Of California San Diego

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion

• history of Diagnostic and Statistical Manual (DSM-IV) diagnosis of anorexia or bulimia.
• AN women have history of average body weight (ABW) below 85% for height.
• AN-BN subjects have history of ABW below 85% ABW.
• AN-BN subjects have history of binging/purging behaviors during a period of low weight.
• Subjects must be right-handed.
• Subjects have been recovered for 12 months or more.

Exclusion

• Diagnosis of alcohol or drug abuse or dependence in the 3 months.
• Alcohol or substance use within 30 days.
• Current diagnosis of an Axis I disorder.
• Organic brain syndromes, dementia, psychotic disorders, or mental retardation.
• Neurological or medical disorders such as seizure disorder, renal disease, diabetes, thyroid disease, EKG indicative of electrolyte imbalance
• BN subjects whose purging methods were the use of laxatives, diuretics
• Use of psychoactive medication in the 3 months.
• Pregnancy or lactation.
• Tobacco use in the 3 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: [11C]raclopride, [11C]DASB, amphetamine; One time administration of oral amphetamine based on subject's weight (0.5 mg/kg). One PET scan using [11C]DASB. Two PET scans using [11C]raclopride.

Drug: [11C]raclopride; 1.[11C]raclopride -The change (Δ) in BPND (the difference between the [11C]raclopride BPND at baseline and post-AMPH treatment normalized to the baseline BPND; Other Names: Raclopride, serial number 009; Drug: [11C]DASB; BPND of [11C]DASB.; Other Names: DASB, serial number 0011; Drug: amphetamine; The change (Δ) in BPND (the difference between the [11C]raclopride BPND at baseline and post-AMPH treatment normalized to the baseline BPND.; Other Names: dextroamphetamine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
5-HT Transporter Binding as Measured During the PET Scan	Use PET and [11C]DASB to explore 5-HTT receptor binding potential midbrain and striatal regions of interest in eating disorder subtypes. The Binding Potential (BP) was calculated as BP Non Displaceable (ND) = (VT/VND) -1. [VT = distribution volume in tissue; VND = non-displaceable distribution volume]. The binding of the 5-HTT on PET presumably reflects 5-HTT density and/or affinity.	90 minute PET scan

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dopamine D2/D3 Receptor Binding as Measured During the PET Scan After Amphetamine Administration	Use PET and [11C]raclopride to explore Dopamine D2/D3 receptor binding potential (BPND) in striatal regions of interest in eating disorder subtypes after amphetamine administration. The Binding Potential (BP) was calculated as BP Non Displaceable (ND) = (VT/VND) -1. [VT = distribution volume in tissue; VND = non-displaceable distribution volume].	90 min PET scan

Collaborators and Investigators

• Sponsor: University of California, San Diego
• Collaborators: National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: Walter Kaye, MD, UCSD; Principal Investigator: Ursula Bailer, MD, UCSD

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Actual): December 31, 2017
• Study Completion (Actual): December 31, 2017

Study Registration Dates

• First Submitted: December 11, 2013
• First Submitted That Met QC Criteria: December 18, 2013
• First Posted (Estimate): December 24, 2013

Study Record Updates

• Last Update Posted (Actual): April 27, 2020
• Last Update Submitted That Met QC Criteria: April 7, 2020
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Feeding and Eating Disorders; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Dopamine Antagonists; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Sympathomimetics; Adrenergic Uptake Inhibitors; Amphetamine; Dextroamphetamine; Raclopride
• Other Study ID Numbers: 090661; R01MH092793 (U.S. NIH Grant/Contract)