Monoamine Contributions to Neurocircuitry in Eating Disorders

• ClinicalTrials.gov Identifier: NCT02020408
• Recruitment Status: Completed
• First Posted: December 24, 2013
• Results First Posted: April 27, 2020
• Last Update Posted: April 27, 2020
• Sponsor: University of California, San Diego
• Collaborator: National Institute of Mental Health (NIMH)
• Information provided by (Responsible Party): Walter Kaye, University of California, San Diego

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Eating Disorder	Drug: [11C]raclopride; Drug: [11C]DASB; Drug: amphetamine	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 88 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Monoamine Contributions to Neurocircuitry in Eating Disorders
• Study Start Date: May 2011
• Actual Primary Completion Date: December 31, 2017
• Actual Study Completion Date: December 31, 2017

Arms and Interventions

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 Name: Raclopride, serial number 009; Drug: [11C]DASB; BPND of [11C]DASB.; Other Name: 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 Name: dextroamphetamine

Outcome Measures

Primary Outcome Measures :

1. 5-HT Transporter Binding as Measured During the PET Scan [ Time Frame: 90 minute 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.

Secondary Outcome Measures :

1. Dopamine D2/D3 Receptor Binding as Measured During the PET Scan After Amphetamine Administration [ Time Frame: 90 min PET scan ]
   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].

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Locations

United States, California

University of California San Diego

San Diego, California, United States, 92102

Sponsors and Collaborators

University of California, San Diego

National Institute of Mental Health (NIMH)

Investigators

• Principal Investigator: Walter Kaye, MD; UCSD
• Principal Investigator: Ursula Bailer, MD; UCSD

  Study Documents (Full-Text)

Documents provided by Walter Kaye, University of California, San Diego:

Study Protocol and Statistical Analysis Plan  [PDF] September 9, 2015

More Information

• Responsible Party: Walter Kaye, MD, University of California, San Diego
• ClinicalTrials.gov Identifier: NCT02020408
• Other Study ID Numbers: 090661; R01MH092793 ( U.S. NIH Grant/Contract )
• First Posted: December 24, 2013
• Results First Posted: April 27, 2020
• Last Update Posted: April 27, 2020
• Last Verified: December 2019

Additional relevant MeSH terms:

Feeding and Eating Disorders; Mental Disorders; Raclopride; Amphetamine; Dextroamphetamine; Central Nervous System Stimulants; Physiological Effects of Drugs; Sympathomimetics; Autonomic Agents; Peripheral Nervous System Agents; Dopamine Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Adrenergic Agents; Adrenergic Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Uptake Inhibitors; Antipsychotic Agents; Tranquilizing Agents; Central Nervous System Depressants; Psychotropic Drugs; Dopamine Antagonists