The Gut-brain Axis: a Novel Target for Treating Behavioral Alterations in Obesity

NCT01976156 | Completed DMC

• 2 other identifiers: 13080125371R01CA180030
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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).

Conditions

Neural Response in Caudate; Weight Loss Trial; Impulsivity

Outcome Measures

Primary Outcomes (4)

• Change in neural response

  change in neural response to milkshake stimulus will be measured with functional magnetic resonance imaging

  6 weeks, 5.5 months, 9.5 months

• 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

  5.5 months

• 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).

  6 weeks, 5.5 months, 9.5 months

• Change in impulsivity

  Various questionnaires and computer tasks addressing impulsivity

  6 weeks, 5.5 months, 9.5 months

Secondary Outcomes (1)

• Baseline brain

  0 weeks (baseline)

Study Arms (2)

Phopsholean dietary supplement

EXPERIMENTAL

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

Placebo (rice flour) group

PLACEBO COMPARATOR

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

Dietary Supplement: Placebo

Interventions

PhosphoLean DIETARY_SUPPLEMENT

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).

Phopsholean dietary supplement

Placebo DIETARY_SUPPLEMENT

Placebo consists of rice flour

Placebo (rice flour) group

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Yale University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

The John B Pierce Laboratory

New Haven, Connecticut, 06519, United States

Location

Related Publications (11)

• 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.

  PMID: 18927395 BACKGROUND

• 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.

  PMID: 10395223 BACKGROUND

• 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.

  PMID: 12497624 BACKGROUND

• 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.

  PMID: 2069496 BACKGROUND

• 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.

  PMID: 9672901 BACKGROUND

• 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.

  PMID: 12587665 BACKGROUND

• 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.

  PMID: 9429233 BACKGROUND

• 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.

  PMID: 20881128 BACKGROUND

• 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.

  PMID: 21430137 BACKGROUND

• 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.

  PMID: 18590587 BACKGROUND

• 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.

  PMID: 23033919 BACKGROUND

MeSH Terms

Conditions

Impulsive Behavior

Condition Hierarchy (Ancestors)

Behavior

Study Officials

• Dana M Small, PhD

  The John B. Pierce Laboratory

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2013
• First Posted: November 5, 2013
• Study Start: October 1, 2013
• Primary Completion: October 1, 2017
• Study Completion: October 1, 2017
• Last Updated: June 27, 2018

Record last verified: 2018-06

Locations

US (1)