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

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ClinicalTrials.gov Identifier: NCT01976156
Recruitment Status : Completed
First Posted : November 5, 2013
Last Update Posted : June 27, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Yale University

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).


Condition or disease Intervention/treatment Phase
Neural Response in Caudate Weight Loss Trial Impulsivity Dietary Supplement: PhosphoLean Dietary Supplement: Placebo Not Applicable

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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: The Gut-brain Axis: a Novel Target for Treating Behavioral Alterations in Obesity
Study Start Date : October 2013
Actual Primary Completion Date : October 2017
Actual Study Completion Date : October 2017

Arm Intervention/treatment
Experimental: Phopsholean dietary supplement
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.
Dietary Supplement: PhosphoLean
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).

Placebo Comparator: Placebo (rice flour) group
The control (placebo) group will receive a placebo (identical in appearance, but containing 100 mg of rice flour per capsule).
Dietary Supplement: Placebo
Placebo consists of rice flour




Primary Outcome Measures :
  1. Change in neural response [ Time Frame: 6 weeks, 5.5 months, 9.5 months ]
    change in neural response to milkshake stimulus will be measured with functional magnetic resonance imaging

  2. 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 [ Time Frame: 5.5 months ]
    attendance to coaching sessions and food diaries will be used to measure adherence

  3. Change in fat and sweet preference and intake [ Time Frame: 6 weeks, 5.5 months, 9.5 months ]
    Subject will be asked to sample and rate fatty and sweet flavor stimuli (all made from commercially available ingredients).

  4. Change in impulsivity [ Time Frame: 6 weeks, 5.5 months, 9.5 months ]
    Various questionnaires and computer tasks addressing impulsivity


Secondary Outcome Measures :
  1. Baseline brain [ Time Frame: 0 weeks (baseline) ]
    perceptual and cognitive measures will be associated with diet, insulin sensitivity and may vary with genotype (TaqA1 1A polymorphism)



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


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): NCT01976156


Locations
United States, Connecticut
The John B Pierce Laboratory
New Haven, Connecticut, United States, 06519
Sponsors and Collaborators
Yale University
National Cancer Institute (NCI)
Investigators
Principal Investigator: Dana M Small, PhD The John B. Pierce Laboratory

Publications:

Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT01976156     History of Changes
Other Study ID Numbers: 1308012537
1R01CA180030 ( U.S. NIH Grant/Contract )
First Posted: November 5, 2013    Key Record Dates
Last Update Posted: June 27, 2018
Last Verified: June 2018

Additional relevant MeSH terms:
Weight Loss
Impulsive Behavior
Body Weight Changes
Body Weight
Signs and Symptoms