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The Gut-brain Axis: a Novel Target for Treating Behavioral Alterations in Obesity (CIDO OEA)

Primary Purpose

Neural Response in Caudate, Weight Loss Trial, Impulsivity

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
PhosphoLean
Placebo
Sponsored by
Yale University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Neural Response in Caudate

Eligibility Criteria

18 Years - 45 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Right handed, English speaking, be a non-smoker (never smoked more than 2 cigarettes per month). Subjects will have a Body Mass Index > 25 kg/m2 (overweight/obese). Subjects are in good health. Subjects are able to provide a letter from their physician stating that they have had a physical exam in the past year and are in general good health and have specifically tested in the normal range for thyroid function and Hemoglobin 1Ac (and as such do not suffer from common metabolic disorders). In addition to this we will at intake confirm normal blood pressure, blood sugar and electrolyte balance for every subject.

Exclusion Criteria:

a) serious or unstable medical illness (e.g., cancer); b) past or current history of alcoholism or consistent drug use; c) current and history of major psychiatric illness as defined by the Diagnostic and Statistical Manual Diploma in Social Medicine-IV criteria including eating disorders, d) medications that affect alertness (e.g., barbiturates, benzodiazepines, chloral hydrate, haloperidol, lithium, carbamazepine, phenytoin, etc.)and any psychoactive drugs or anti-obesity agents; e) history of major head trauma with loss of consciousness; f) ongoing pregnancy; g) known taste or smell dysfunction; h) a diagnosis of diabetes; i) any known food allergy, certain food sensitivities (lactose); j) pregnant or nursing women, k) history of metalworking, injury with shrapnel or metal slivers, and major surgery; l) history of pacemaker or neurostimulator implantation.

Sites / Locations

  • The John B Pierce Laboratory

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Phopsholean dietary supplement

Placebo (rice flour) group

Arm Description

Subjects in the Phospholean group will receive six capsules of PhosphoLean orally daily (total of 180 mg of NOPE and 120 mg of EGCG), ); two capsules consumed one hour before lunch, two capsules one hour prior to dinner, and two capsules two hours after dinner.

The control (placebo) group will receive a placebo (identical in appearance, but containing 100 mg of rice flour per capsule).

Outcomes

Primary Outcome Measures

Change in neural response
change in neural response to milkshake stimulus will be measured with functional magnetic resonance imaging
Change in adherence to the behavioral weight loss program, greater weight loss maintenance,and these will be related to impulsivity, fat preference and intake, and striatal response
attendance to coaching sessions and food diaries will be used to measure adherence
Change in fat and sweet preference and intake
Subject will be asked to sample and rate fatty and sweet flavor stimuli (all made from commercially available ingredients).
Change in impulsivity
Various questionnaires and computer tasks addressing impulsivity

Secondary Outcome Measures

Baseline brain
perceptual and cognitive measures will be associated with diet, insulin sensitivity and may vary with genotype (TaqA1 1A polymorphism)

Full Information

First Posted
September 11, 2013
Last Updated
June 25, 2018
Sponsor
Yale University
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT01976156
Brief Title
The Gut-brain Axis: a Novel Target for Treating Behavioral Alterations in Obesity
Acronym
CIDO OEA
Official Title
The Gut-brain Axis: a Novel Target for Treating Behavioral Alterations in Obesity
Study Type
Interventional

2. Study Status

Record Verification Date
June 2018
Overall Recruitment Status
Completed
Study Start Date
October 2013 (undefined)
Primary Completion Date
October 2017 (Actual)
Study Completion Date
October 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Yale University
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The aims of this project are to determine if dietary supplementation with NOPE-EGCG (PhosphoLeantm, 30mg NOPE+20mg EGCG per capsule) can: rescue striatal function, increase adherence to a diet, reduce weight-gain after a diet, improve performance on impulsivity, go/no-go tasks, and negative outcome learning, and shift fat and sweet preference in overweight/obese human subjects Secondary hypotheses: Baseline brain; perceptual and cognitive measures will be associated with diet, insulin sensitivity and may vary with genotype (TaqA1 1A polymorphism).
Detailed Description
In prior studies we have demonstrated an inverse relationship between body mass index and response in the dorsal striatum (DS) during consumption of a palatable milkshake (Stice et al. 2008). We have also shown that the magnitude of the reduced response predicts weight gain, especially in individuals who carry a copy of the A1 allele of the taq1A polymorphism (Stice et al. 2008). Since the A1 allele is associated with reduced striatal D2 receptors (Jonsson et al. 1999, Noble 2003, Noble et al. 1991, Pohjalainen et al. 1998, Ritchie et al. 1998, Thompson et al. 1997), this finding implicates the dopamine system in the reduced blood oxygen level dependent (BOLD) response. Our results also indicate that this reduced response is a consequence, rather than a cause of obesity, since gaining weight (Stice et al. 2010), but not risk for obesity (Stice et al. 2011) (by virtue of parental obesity), is associated with reduced DS response to palatable food. Taken together the results indicate that increased adiposity is associated with blunted DS response to palatable food that may reflect altered dopamine signaling. More recently we determined that reduced DS responses in overweight and obese subjects are associated with increased impulsivity measured with the Barratt Impulsiveness Scale and a go no/no-go task (Babbs et al, In Press). Related to these findings in humans, preliminary work in rodents shows that exogenous administration of N-Acylethanolamines, such as oleoylethanolamine (OEA) can normalize high-fat diet induced dopamine decreases in DS and possibly induce a shift in preference (Tellez et al., In Press). Human testing of OEA supplementation is possible based on the availability of a dietary supplement containing the OEA precursor NOPE-EGCG ((PhosphoLEANtm, 100 mg NOPE+50mg EGCG per capsule). PhosphoLEAN has been shown to enhance adherence to dietary advice in overweight healthy subjects (Rondanelli et al. 2009, Mangine et al. 2012). We therefore propose a double-blind cross-over study to test whether PhosphoLean will rescue striatal function, increase adherence to a diet, reduce weight-gain after a diet, improve performance on impulsivity, go/no-go tasks, and negative outcome learning, and shift fat and sweet preference in overweight/obese human subjects.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neural Response in Caudate, Weight Loss Trial, Impulsivity

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
100 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Phopsholean dietary supplement
Arm Type
Experimental
Arm Description
Subjects in the Phospholean group will receive six capsules of PhosphoLean orally daily (total of 180 mg of NOPE and 120 mg of EGCG), ); two capsules consumed one hour before lunch, two capsules one hour prior to dinner, and two capsules two hours after dinner.
Arm Title
Placebo (rice flour) group
Arm Type
Placebo Comparator
Arm Description
The control (placebo) group will receive a placebo (identical in appearance, but containing 100 mg of rice flour per capsule).
Intervention Type
Dietary Supplement
Intervention Name(s)
PhosphoLean
Intervention Description
PhosphoLean supplied by Cheminutra (White Bear Lake, MN). PhosphoLean® N-Oleoyl-PE + EGCG (NOPE + EGCG) is a proprietary phosphobioflavonic complex of N-oleoyl-phosphatidyl-ethanolamine (NOPE), which contains oleoyl ethanolamine (OEA) bound to phosphatidylethanolamine (PE), and epigallocatechin gallate (EGCG).
Intervention Type
Dietary Supplement
Intervention Name(s)
Placebo
Intervention Description
Placebo consists of rice flour
Primary Outcome Measure Information:
Title
Change in neural response
Description
change in neural response to milkshake stimulus will be measured with functional magnetic resonance imaging
Time Frame
6 weeks, 5.5 months, 9.5 months
Title
Change in adherence to the behavioral weight loss program, greater weight loss maintenance,and these will be related to impulsivity, fat preference and intake, and striatal response
Description
attendance to coaching sessions and food diaries will be used to measure adherence
Time Frame
5.5 months
Title
Change in fat and sweet preference and intake
Description
Subject will be asked to sample and rate fatty and sweet flavor stimuli (all made from commercially available ingredients).
Time Frame
6 weeks, 5.5 months, 9.5 months
Title
Change in impulsivity
Description
Various questionnaires and computer tasks addressing impulsivity
Time Frame
6 weeks, 5.5 months, 9.5 months
Secondary Outcome Measure Information:
Title
Baseline brain
Description
perceptual and cognitive measures will be associated with diet, insulin sensitivity and may vary with genotype (TaqA1 1A polymorphism)
Time Frame
0 weeks (baseline)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Right handed, English speaking, be a non-smoker (never smoked more than 2 cigarettes per month). Subjects will have a Body Mass Index > 25 kg/m2 (overweight/obese). Subjects are in good health. Subjects are able to provide a letter from their physician stating that they have had a physical exam in the past year and are in general good health and have specifically tested in the normal range for thyroid function and Hemoglobin 1Ac (and as such do not suffer from common metabolic disorders). In addition to this we will at intake confirm normal blood pressure, blood sugar and electrolyte balance for every subject. Exclusion Criteria: a) serious or unstable medical illness (e.g., cancer); b) past or current history of alcoholism or consistent drug use; c) current and history of major psychiatric illness as defined by the Diagnostic and Statistical Manual Diploma in Social Medicine-IV criteria including eating disorders, d) medications that affect alertness (e.g., barbiturates, benzodiazepines, chloral hydrate, haloperidol, lithium, carbamazepine, phenytoin, etc.)and any psychoactive drugs or anti-obesity agents; e) history of major head trauma with loss of consciousness; f) ongoing pregnancy; g) known taste or smell dysfunction; h) a diagnosis of diabetes; i) any known food allergy, certain food sensitivities (lactose); j) pregnant or nursing women, k) history of metalworking, injury with shrapnel or metal slivers, and major surgery; l) history of pacemaker or neurostimulator implantation.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dana M Small, PhD
Organizational Affiliation
The John B. Pierce Laboratory
Official's Role
Principal Investigator
Facility Information:
Facility Name
The John B Pierce Laboratory
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06519
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
18927395
Citation
Stice E, Spoor S, Bohon C, Small DM. Relation between obesity and blunted striatal response to food is moderated by TaqIA A1 allele. Science. 2008 Oct 17;322(5900):449-52. doi: 10.1126/science.1161550.
Results Reference
background
PubMed Identifier
10395223
Citation
Jonsson EG, Nothen MM, Grunhage F, Farde L, Nakashima Y, Propping P, Sedvall GC. Polymorphisms in the dopamine D2 receptor gene and their relationships to striatal dopamine receptor density of healthy volunteers. Mol Psychiatry. 1999 May;4(3):290-6. doi: 10.1038/sj.mp.4000532.
Results Reference
background
PubMed Identifier
12497624
Citation
Noble EP. D2 dopamine receptor gene in psychiatric and neurologic disorders and its phenotypes. Am J Med Genet B Neuropsychiatr Genet. 2003 Jan 1;116B(1):103-25. doi: 10.1002/ajmg.b.10005.
Results Reference
background
PubMed Identifier
2069496
Citation
Noble EP, Blum K, Ritchie T, Montgomery A, Sheridan PJ. Allelic association of the D2 dopamine receptor gene with receptor-binding characteristics in alcoholism. Arch Gen Psychiatry. 1991 Jul;48(7):648-54. doi: 10.1001/archpsyc.1991.01810310066012.
Results Reference
background
PubMed Identifier
9672901
Citation
Pohjalainen T, Rinne JO, Nagren K, Lehikoinen P, Anttila K, Syvalahti EK, Hietala J. The A1 allele of the human D2 dopamine receptor gene predicts low D2 receptor availability in healthy volunteers. Mol Psychiatry. 1998 May;3(3):256-60. doi: 10.1038/sj.mp.4000350.
Results Reference
background
PubMed Identifier
12587665
Citation
Ritchie T, Noble EP. Association of seven polymorphisms of the D2 dopamine receptor gene with brain receptor-binding characteristics. Neurochem Res. 2003 Jan;28(1):73-82. doi: 10.1023/a:1021648128758.
Results Reference
background
PubMed Identifier
9429233
Citation
Thompson J, Thomas N, Singleton A, Piggott M, Lloyd S, Perry EK, Morris CM, Perry RH, Ferrier IN, Court JA. D2 dopamine receptor gene (DRD2) Taq1 A polymorphism: reduced dopamine D2 receptor binding in the human striatum associated with the A1 allele. Pharmacogenetics. 1997 Dec;7(6):479-84. doi: 10.1097/00008571-199712000-00006.
Results Reference
background
PubMed Identifier
20881128
Citation
Stice E, Yokum S, Blum K, Bohon C. Weight gain is associated with reduced striatal response to palatable food. J Neurosci. 2010 Sep 29;30(39):13105-9. doi: 10.1523/JNEUROSCI.2105-10.2010.
Results Reference
background
PubMed Identifier
21430137
Citation
Stice E, Yokum S, Burger KS, Epstein LH, Small DM. Youth at risk for obesity show greater activation of striatal and somatosensory regions to food. J Neurosci. 2011 Mar 23;31(12):4360-6. doi: 10.1523/JNEUROSCI.6604-10.2011.
Results Reference
background
PubMed Identifier
18590587
Citation
Rondanelli M, Opizzi A, Solerte SB, Trotti R, Klersy C, Cazzola R. Administration of a dietary supplement ( N-oleyl-phosphatidylethanolamine and epigallocatechin-3-gallate formula) enhances compliance with diet in healthy overweight subjects: a randomized controlled trial. Br J Nutr. 2009 Feb;101(3):457-64. doi: 10.1017/S0007114508024008. Epub 2008 Jul 1.
Results Reference
background
PubMed Identifier
23033919
Citation
Mangine GT, Gonzalez AM, Wells AJ, McCormack WP, Fragala MS, Stout JR, Hoffman JR. The effect of a dietary supplement (N-oleyl-phosphatidyl-ethanolamine and epigallocatechin gallate) on dietary compliance and body fat loss in adults who are overweight: a double-blind, randomized control trial. Lipids Health Dis. 2012 Oct 4;11:127. doi: 10.1186/1476-511X-11-127.
Results Reference
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The Gut-brain Axis: a Novel Target for Treating Behavioral Alterations in Obesity

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