Targeting the Gut-brain Axis to Facilitate Weight Loss in High Fat Diet Consumers

NCT ID: NCT04614233

Last Updated: 2025-01-10

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 64 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-06
• Study Completion Date: 2024-10-04

Brief Summary

The primary objective is to test if fat intake moderates the ability of oleoylethanolamide (OEA) to improve weight loss maintenance after the LEARN® weight loss program.

Detailed Description

The proposed work takes a precision medicine approach to obesity treatment and focuses specifically on weight loss maintenance. We propose to optimize a stratification strategy, using neural, metabolic and behavioral measures to identify individuals who will maintain clinically significant weight loss by daily supplementation with the fatty acid amide, oleoylethanolamide (OEA) following a gold-standard behavioral weight loss program. We will also test a model underlying the efficacy of our intervention to provide insight for the further development of therapeutic avenues. Our first aim is to conduct a randomized double-blind placebo-controlled trial to determine if fat intake moderates the ability of OEA to improve weight loss maintenance after the (LEARN®) weight loss program. We predict fat intake will strongly moderate the ability of OEA to produce clinically significant weight loss and weight loss maintenance 4- and 12-months) after LEARN and that this should not be influenced by sex.

Our second aim is to test if the Dietary Fat and Sugar intake questionnaire (DFS) is associated with measures of saturated fat intake and to optimize a clinically useful stratification strategy. Towards this end we will: (1) perform a neuroimaging study to assess brain response to a high fat milkshake (2) assess blood-based biomarkers of fat intake and synthesis; and (3) collect dietary intake records and food frequency questionnaires (FFQs). We predict that (1) the DFS predicts measures of saturated fat intake (2) that baseline dorsal striatal (DS) response to milkshake predicts weight loss in the OEA but not the placebo group and that connectome based predictive modeling (CPM) reveals a "neural fingerprint" that predicts weight loss on OEA; and (3) LASSO regression will identify baseline measures that best predict outcome to inform selection of a practical clinical stratification recommendation.

Our third aim is to test a model of OEA effectiveness. We predict that weight loss outcome is associated with shifts in fat preference and intake and these effects are mediated by increases in DS response to milkshake in the OEA but not placebo group. We will also test whether high fat diet (HFD) is associated with performance on reinforcement and cognitive measures or changes in energy expenditure or substrate utilization. If so, we will test whether these associations and their reversal by OEA contribute to outcome mediation.

Conditions

Overweight and Obesity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

RiduZone (90% Oleoylethanolamide (OEA))

Participants will be randomly assigned to take 2 capsules of RiduZone (each capsule contains 90% OEA) daily for 16 months.

Group Type: EXPERIMENTAL

RiduZone (90% OEA)

Intervention Type: DIETARY_SUPPLEMENT

Participants will be randomly assigned to take 2 capsules of RiduZone (each capsule contains 90% OEA ) daily for 16 months

Placebo

Participants will be randomly assigned to take 2 capsules of placebo daily for 16 months.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Participants will be randomly assigned to take 2 capsules of placebo daily for 16 months. Placebo capsules will consist of 180mg of hypromellose.

Interventions

RiduZone (90% OEA)

Participants will be randomly assigned to take 2 capsules of RiduZone (each capsule contains 90% OEA ) daily for 16 months

Intervention Type: DIETARY_SUPPLEMENT

Placebo

Participants will be randomly assigned to take 2 capsules of placebo daily for 16 months. Placebo capsules will consist of 180mg of hypromellose.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Ages 18-55
• Right-handed with a score of ≥ +50 on the modified Edinburgh handedness scale
• English-speaking
• BMI > 25.0
• Comfortable with the fMRI procedures during the mock scanning session and rate milkshake as at least mildly liked

Exclusion Criteria

• Serious or unstable medical illness (e.g., cancer)
• Past or current history of alcoholism or consistent drug use
• Current major psychiatric illness as defined by DSM-IV criteria including eating disorders
• Medications that affect alertness (e.g., barbiturates, benzodiazepines, chloral hydrate, haloperidol, lithium, carbamazepine, phenytoin, etc.)
• History of major head trauma with loss of consciousness
• Ongoing pregnancy
• History of metalworking, injury with shrapnel or metal slivers, or major surgery
• History of pacemaker or neurostimulator implantation
• Known taste or smell dysfunction
• A diagnosis of diabetes
• Any known allergy to foods used in the study, or any known life-threatening food allergy
• Tobacco use

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Modern Diet and Physiology Research Lab

New Haven, Connecticut, United States

Countries

United States

References

Fang X, Davis X, Flack KD, Duncan C, Li F, White M, Grilo C, Small DM. Dietary adaptation for weight loss maintenance at Yale (DAWLY): Protocol and predictions for a randomized controlled trial. Front Nutr. 2022 Jul 28;9:940064. doi: 10.3389/fnut.2022.940064. eCollection 2022.

Reference Type: DERIVED

PMID: 35967820 (View on PubMed)

Provided Documents

Document Type: Informed Consent Form

View Document

Other Identifiers

1R01DK126295-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2000028769

Identifier Type: -

Identifier Source: org_study_id