Monoamine Contributions to Neurocircuitry in Eating Disorders

• Sponsor: University of California, San Diego (Other)
• Overall Status: Completed
• CT.gov ID: NCT02020408
• Collaborator: National Institute of Mental Health (NIMH) (NIH)
• Enrollment: 88
• Location: 1
• Arm: 1
• Duration (Months): 80
• Patients Per Site Per Month: 1.1

Study Details

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
• 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 1, 2011
• Actual Primary Completion Date: Dec 31, 2017
• Actual Study Completion Date: Dec 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 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

Outcome Measures

Primary Outcome Measures

1. 5-HT Transporter Binding as Measured During the PET Scan [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 [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

Criteria

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

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

	Site	City	State	Country	Postal Code
1	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)

• Study Protocol and Statistical Analysis Plan - Sep 9, 2015

More Information

Publications

None provided.

• Responsible Party: Walter Kaye, MD, University of California, San Diego
• ClinicalTrials.gov Identifier: NCT02020408
• Other Study ID Numbers: 090661; R01MH092793
• First Posted: Dec 24, 2013
• Last Update Posted: Apr 27, 2020
• Last Verified: Dec 1, 2019

• Additional relevant MeSH terms: Feeding and Eating Disorders; Raclopride; Amphetamine; Dextroamphetamine

Study Results

Participant Flow

Arm/Group Title	[11C]Raclopride, [11C]DASB, Amphetamine
Arm/Group Description	healthy control women (CW); women recovered from restricting type anorexia nervosa (REC AN); women recovered from bulimic type anorexia nervosa (REC AN-BN) women recovered from from bulimia nervosa (REC BN)
Period Title: Overall Study
STARTED	88
COMPLETED	85
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	[11C]Raclopride, [11C]DASB, Amphetamine
Arm/Group Description	healthy control women (CW); women recovered from restricting type anorexia nervosa (REC AN); women recovered from bulimic type anorexia nervosa (REC AN-BN) women recovered from from bulimia nervosa (REC BN)
Overall Participants	85
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	85 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	85 100%
Male	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	12 14.1%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 1.2%
White	72 84.7%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	85 100%

Outcome Measures

1. Primary Outcome

Title	5-HT Transporter Binding as Measured During the PET Scan
Description	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.
Time Frame	90 minute PET scan

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	[11C]DASB Binding Potential Control Women	[11C]DASB Binding Potential in REC AN	[11C]DASB Binding Potential in REC ANBN	[11C]DASB Binding Potential in REC BN
Arm/Group Description	[11C] DASB Binding potential (BPND) in control women (healthy controls)	[11C]DASB binding potential in women recovered from restricting type anorexia nervosa (REC AN)	[11C]DASB binding potential in women recovered from bulimic type anorexia nervosa (REC AN-BN)	[11C]DASB binding potential in women recovered from bulimia nervosa (REC BN)
Measure Participants	24	18	16	8
[11C]DASB BPND anteroventral striatum	1.68 (0.26)	1.54 (0.32)	1.46 (0.47)	1.60 (0.34)
[11C]DASB BPND post dorsal caudate	0.44 (0.15)	0.35 (0.18)	0.39 (0.16)	0.37 (0.19)
[11C]DASB BPND posterior putamen	1.36 (0.25)	1.27 (0.18)	1.17 (0.39)	1.32 (0.29)
[11C]DASB BPND predorsal caudate	1.08 (0.19)	0.99 (0.32)	0.99 (0.34)	0.98 (0.30)
[11C]DASB BPND anterior putamen	1.70 (0.26)	1.59 (0.26)	1.49 (0.48)	1.57 (0.28)
[11C]DASB BPND midbrain	2.21 (0.31)	2.06 (0.30)	1.98 (0.60)	2.17 (0.19)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	[11C]DASB Binding Potential Control Women, [11C]DASB Binding Potential in REC AN, [11C]DASB Binding Potential in REC ANBN, [11C]DASB Binding Potential in REC BN
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	> 0.05
	Comments	The p value was calculated and adjusted for multiple comparisons (Bonferroni).
	Method	ANOVA
	Comments

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Due to technical problems and temporary closure of the PET Facility during the study and consequent lack of time and funding for additional scanning, we were unable to recruit a sufficient number of women recovered from bulimia nervosa (BN) for the AMPHETAMINE CHALLENGE STUDY and therefore no data for this outcome measure were collected in REC BN.

Arm/Group Title	[11C]Raclopride Binding Potential Control Women	[11C]Raclopride Binding Potential in REC AN	[11C]Raclopride Binding Potential in REC ANBN
Arm/Group Description	[11C]raclopride binding potential in control women after amphetamine administration	[11C]raclopride binding potential in women recovered from restricting type anorexia nervosa (REC AN) after amphetamine administration	[11C]raclopride binding potential in womenrecovered from bulimic type anorexia nervosa (REC ANBN) after amphetamine administration
Measure Participants	14	13	5
[11C]raclopride BPND anteroventral striatum	2.09 (0.22)	2.01 (0.15)	1.94 (0.37)
[11C]raclopride BPND post dorsal caudate	1.69 (0.27)	1.62 (0.19)	1.69 (0.34)
[11C]raclopride BPND anterior putamen	2.71 (0.26)	2.65 (0.22)	2.60 (0.40)
[11C]raclopride BPND posterior putamen	2.53 (0.32)	2.46 (0.26)	2.47 (0.40)
[11C]raclopride BPND predorsal caudate	2.48 (0.30)	2.40 (0.14)	2.47 (0.47)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	[11C]DASB Binding Potential Control Women, [11C]DASB Binding Potential in REC AN, [11C]DASB Binding Potential in REC ANBN
	Comments	A General Linear Model using log([11C]raclopride BPND) after amphetamine administration as dependent variable and Diagnostic Group as independent variable was used. Baseline (before amphetamine administration) [11C]raclopride BPND was used as covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments	The p value was calculated and adjusted for multiple comparisons (Bonferroni).
	Method	General Linear Model
	Comments

Adverse Events

Time Frame	5 years
Arm/Group Title	[11C]Raclopride, [11C]DASB, Amphetamine
Arm/Group Description	healthy control women (CW); women recovered from restricting type anorexia nervosa (REC AN); women recovered from bulimic type anorexia nervosa (REC AN-BN) women recovered from from bulimia nervosa (REC BN)
All Cause Mortality
	[11C]Raclopride, [11C]DASB, Amphetamine
	Affected / at Risk (%)	# Events
Total	0/85 (0%)
Serious Adverse Events
	[11C]Raclopride, [11C]DASB, Amphetamine
	Affected / at Risk (%)	# Events
Total	0/85 (0%)
Other (Not Including Serious) Adverse Events
	[11C]Raclopride, [11C]DASB, Amphetamine
	Affected / at Risk (%)	# Events
Total	2/85 (2.4%)
Cardiac disorders
High blood pressure	2/85 (2.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.