The Gut-brain Axis: a Novel Target for Treating Behavioral Alterations in Obesity (CIDO OEA)
|ClinicalTrials.gov Identifier: NCT01976156|
Recruitment Status : Completed
First Posted : November 5, 2013
Last Update Posted : January 17, 2018
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 in a double-blind cross-over design.
|Condition or disease||Intervention/treatment||Phase|
|Neural Response in Caudate Weight Loss Trial Impulsivity||Dietary Supplement: PhosphoLean Dietary Supplement: Placebo||Not Applicable|
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)|
|Estimated Enrollment :||168 participants|
|Intervention Model:||Crossover 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|
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), one capsule consumed midway between lunch and dinner, 60 minutes prior to dinner and one capsule 2 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
- Change in neural response [ Time Frame: 6 weeks, 6.5 months, 10.5 months, 14.5 months ]change in neural response to milkshake stimulus will be measured with functional magnetic resonance imaging
- Change in weight [ Time Frame: 6 weeks, 6.5 months, 10.5 months, 14.5 months ]Change in body weight, body mass index and body fat percentage will be determined
- Change in adherence to low-calorie diet [ Time Frame: 6.5 months ]attendance to coaching sessions and food diaries will be used to measure adherence
- Change in fat and sweet preference [ Time Frame: 6 weeks, 6.5 months, 10.5 months, 14.5 months ]Subject will be asked to sample and rate fatty and sweet flavor stimuli (all made from commercially available ingredients).
- Change in impulsivity [ Time Frame: 6 weeks, 6.5 months, 10.5 months, 14.5 months ]Various questionnaires and computer tasks addressing impulsivity
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01976156
|United States, Connecticut|
|The John B Pierce Laboratory|
|New Haven, Connecticut, United States, 06519|
|Principal Investigator:||Dana M Small, PhD||The John B. Pierce Laboratory|