The Gut-brain Axis in Food Reward and Alcohol Consumption

Alcohol Consumption Clinical Trial

Official title:

The Gut-brain Axis in Food Reward and Alcohol Consumption

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01902069
• Other study ID #: 1305012106
• Secondary ID: 5P50AA012870
• Status: Completed
• Phase: N/A
• Start date: July 2013
• Est. completion date: November 2014

Study information

• Verified date: April 2020
• Source: Yale University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aims of this project are to:

1. Determine if 3-weeks dietary supplementation with NOPE-EGCG (PhosphoLEANtm, 85mg NOPE+50mg EGCG per capsule) versus a placebo will improve performance on impulsivity, go/no-go tasks and negative outcome learning in heavy drinkers.

2. Evaluate whether supplementation with NOPE-EGCG versus placebo results in reductions in alcohol consumption.

3. Preliminary data in the rodent model suggests that rats treated with OEA shift preference for lower fat test stimuli. In aim 3 we will Determine if 3-weeks of supplementation with PhosphoLEAN shifts fat preference towards lower fat test puddings.

Description:

Similarities in striatocortical pathway dysfunction have been noted for alcoholism and obesity. 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[1]. 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[1]. Since the A1 allele is associated with reduced striatal D2 receptors [2-7], 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 [8], but not risk for obesity [9] (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 BIS-11 and a go no/no-go task [10]. Heavy drinkers are also more likely to be impulsive [11]. In preliminary analyses of data on over 300 individuals assessed with the clinical core battery in the Center for the Translational Neuroscience of Alcoholism (CTNA), we found that higher scores on the BIS-11 and other measures of impulsivity were associated with greater alcohol consumption.

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. Human testing of OEA supplementation is possible based on the availability of a dietary supplement containing the OEA precursor NOPE-EGCG ((PhosphoLEANtm, 85mg NOPE+50mg EGCG per capsule). PhosphoLEAN has been shown to enhance adherence to dietary advice in overweight healthy subjects [12-14]. We therefore propose a pilot study to test whether PhosphoLEAN will improve performance on impulsivity, go/no-go tasks and negative outcome learning. Specifically, we will recruit heavy drinkers because they are more likely to be impulsive [11]. Phospholean may improve negative reinforcement learning in this population. This may lead to reductions in drinking as well. We will also explore whether the supplement leads to reductions in alcohol consumption and preference for high fat foods.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: November 2014
• Est. primary completion date: November 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years to 45 Years

Eligibility

Inclusion Criteria:

• Subjects meeting NIAAA heavy drinking criteria (for men defined as consuming 5 or more standard drinks on a drinking day and for women as consuming 4 or more standard drinks on a drinking day at least once per week for the prior 30 days, with an upper limit of 40 standard drinks per week). Half will be women. Right handed, English speaking, be a non-smoker (never smoked more than 2 cigarettes per month). Subjects will have a BMI between 18.5 and 35.

Exclusion Criteria:

• a) serious or unstable medical illness (e.g., cancer); b) past or current history of alcoholism or consistent drug use; c) current major psychiatric illness as defined by the DSM-IV criteria including eating disorders d) medications that affect alertness (e.g., barbiturates, benzodiazepines, chloral hydrate, haloperidol, lithium, carbamazepine, phenytoin, etc.); 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. Daily drinkers and individuals meeting criteria for alcohol dependence will be excluded.

Related Conditions & MeSH terms

• Alcohol Consumption
• Alcohol Drinking
• Impulsive Behavior
• Impulsivity

Intervention

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). PhosphoLean® 40P is a dietary ingredient under the Dietary Supplement Health and Education Act (DSHEA) regulations of the US FDA (1994).
• Placebo
Placebo consists of rice flour

Locations

Country	Name	City	State
United States	John B Pierce Laboratory	New Haven	Connecticut

Sponsors (2)

Lead Sponsor	Collaborator
Yale University	National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Fat and sweet preference	Subject will be asked to sample and rate fatty and sweet flavor stimuli (all made from commercially available ingredients).	21 days
Primary	Impulsivity	Various questionnaires and computer tasks addressing impulsivity.	21 days
Primary	Alcohol consumption	Interview addressing alcohol consumption	21 days