Clinical trial NCT04614233: Targeting the Gut-brain Axis to Facilitate Weight Loss in High Fat Diet Consumers
Official title: Targeting the Gut-brain Axis to Facilitate Weight Loss in High Fat Diet Consumers
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Overweight and Obesity
Keywords: high-fat diet consumers
gut-brain axis
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2020-11-03
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Investigators are testing the hypotheses that high fat diet consumers will show the greatest benefit from supplementation with oleoylethanolamide (OEA) in terms of weight loss maintenance, because OEA targets brain adaptations that are related to high fat diet.
Primary purpose: BASIC_SCIENCE

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.

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

Primary outcomes:
measure: Percent change in body weight
timeFrame: Baseline, 4 month, 8 month, and 16 months
measure: Change in absolute body weight
timeFrame: Baseline, 4 month, 8 month, and 16 months
measure: Change in waist circumference
timeFrame: Baseline, 4 month, 8 month, 16 month
measure: Change in hip circumference
timeFrame: Baseline, 4 month, 8 month, and 16 months
measure: Change in thigh circumference
timeFrame: Baseline, 4 month, 8 month, and 16 months
measure: Change in body fat percent
timeFrame: Baseline, 4 month, 8 month, and 16 months
measure: Change in visceral adipose tissue
timeFrame: Baseline, 4 month, 8 month, 16 month
measure: Change in saturated fat intake as measured by the DFS
timeFrame: Baseline, 4 month, 8 month, and 16 months
measure: Change in saturated fat intake as measured by the ASA24
timeFrame: Baseline, 4 month, 8 month, and 16 months
measure: Change in total saturated fat intake as measured by 3-day food diaries
timeFrame: Baseline, 4 month, 8 month, and 16 months
measure: Change in total fat intake as measured by 3-day food diaries
timeFrame: Baseline, 4 month, 8 month, and 16 months
measure: Change in total saturated fat intake as measured by C-reactive protein
timeFrame: Baseline, 8 month
measure: Change in brain response to milkshake
timeFrame: baseline, 8 month
measure: Change in fat perception with Visual Analogue Scale
timeFrame: Baseline, 4 month, 8 month, and 16 months
measure: Change in fat perception with General Labeled Magnitude Scale
timeFrame: Baseline, 4 month, 8 month, and 16 months
measure: Change in fat preference with Labeled Hedonic Scale
timeFrame: Baseline, 4 month, 8 month, and 16 months
measure: Change in sensitivity to the long-chain oleic acid C18:1 - measured by a 3-alternative forced choice test
timeFrame: Baseline, 4 month, 8 month, 16 month
measure: Change in sugar perception with General Labeled Magnitude Scale
timeFrame: Baseline, 4 month, 8 month, and 16 months
measure: Change in sugar preference with Labeled Hedonic Scale
timeFrame: Baseline, 4 month, 8 month, and 16 months
measure: Change in fat concentration preference measured by the Monell forced choice test
timeFrame: Baseline, 4 month, 8 month, and 16 months
measure: Change in sweet concentration preference measured by the Monell forced choice test
timeFrame: Baseline, 4 month, 8 month, and 16 months
measure: Change in food reinforcement with RED-13
timeFrame: Baseline and 8 month
measure: Change in food reinforcement with Becker DeGroot Markov Auction Task
timeFrame: Baseline and 8 month
measure: Change in cognition with Kirby Delay Discounting
timeFrame: Baseline, 4 month, 8 month, and 16 months
measure: Change in cognition with the Relational Task
timeFrame: Baseline, 4 month, 8 month, and 16 months
measure: Change in cognition with Penn Progressive Matrices Test
timeFrame: Baseline, 4 month, 8 month, and 16 months
measure: Change in cognition with Oral Reading Recognition Test
timeFrame: Baseline, 4 month, 8 month, and 16 months
measure: Change in cognition with Variable Short Penn Line Orientation Test
timeFrame: Baseline, 4 month, 8 month, and 16 months
measure: Change in cognition with Matrix Reasoning Task (Core NMOB)
timeFrame: Baseline, 4 month, 8 month, and 16 months
measure: Change in cognition with Digit Symbol Substitution (Core NMOB)
timeFrame: Baseline, 4 month, 8 month, and 16 months
measure: Change in cognition with Go/No-Go Task (Core NMOB)
timeFrame: Baseline, 4 month, 8 month, and 16 months
measure: Change in cognition with Penn Word Memory Test
timeFrame: Baseline, 4 month, 8 month, and 16 months
measure: Change in cognition with Dimensional Change Card Sorting (Core NMOB)
timeFrame: Baseline, 4 month, 8 month, and 16 months
measure: Change in cognition with Picture Sequence Memory (Core NMOB)
timeFrame: Baseline, 4 month, 8 month, and 16 months
measure: Change in cognition with Stockings of Cambridge (SOC) test (CANTAB)
timeFrame: Baseline, 4 month, 8 month, and 16 months
measure: Change in cognition with Intra-Extra Dimensional Set Shift test (CANTAB)
timeFrame: Baseline, 4 month, 8 month, and 16 months
measure: Change in cognition with delayed non-matching to sample test (CANTAB)
timeFrame: Baseline, 4 month, 8 month, and 16 months
measure: Change in cognition with Paired Associates Learning task (CANTAB)
timeFrame: Baseline, 4 month, 8 month, and 16 months
measure: Change in cognition with Probabilistic-Feedback Reward Task
timeFrame: Baseline, 4 month, 8 month, and 16 months
measure: Change in resting energy expenditure
timeFrame: Baseline and 8 month
measure: Change in respiratory exchange ratio
timeFrame: Baseline and 8 month
Secondary outcomes:
measure: Change in Healthy Eating Index (HEI)
timeFrame: Baseline, 4 month, 8 month, 16 month
measure: Change in 3-day food diary total solid fat intake
timeFrame: Baseline, 4 month, 8 month, 16 month
measure: Change in saturated fat intake measured by plasma cholesterol
timeFrame: Baseline, 8 month
measure: Change in saturated fat intake measured by plasma triglycerides
timeFrame: Baseline, 8 month
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Modern Diet and Physiology Research Lab
state: Connecticut
Study officials:
References:
citation: 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.