Evaluation of Botanicals for Mechanisms Related to Appetite and Fat Metabolism

NCT02333461 | Completed

• 1 other identifier: BURN CURB POM-1
• Study Type: interventional
• Target: 90
• Locations: 0 countries
• Sites: N/A

Brief Summary

Excess caloric consumption, particularly from inexpensive, energy dense foods that are high in fat and refined carbohydrates, is a major driver of the global obesity epidemic. Dietary supplements that promote reduced intake of energy dense foods and/or impact the absorption and metabolism of fat and carbohydrates in the body can be used to help consumers control their weight. We identified two separate mechanistic approaches to target these effects. Diacylglycerol acyltransferase-1 (DGAT-1) is an enzyme involved in the formation of dietary fat into circulating triglycerides within the body. Once dietary fat is digested and absorbed, the resulting fatty acids are re-esterified into triglycerides. Inhibition of DGAT-1 results in delayed and decreased re-esterification of dietary fats into circulating triglycerides. It is hypothesized that this effect may lead to decreased deposition of excess dietary fat as adipose tissue, possibly due to increased fatty acid oxidation in the enterocytes. Ghrelin is a hormone that is known to stimulate appetite in humans. When calorie dense fatty foods are sensed in the stomach, ghrelin is acylated and activated via ghrelin O-acyltransferase (GOAT). The activation step attaches a medium chain fatty acid to the ghrelin molecule that enables it to transmit a signal in the brain that triggers eating and fat storage in adipose tissue. Interfering with the GOAT pathway will inhibit ghrelin activation and possibly diminish food intake and lipid storage. This concept is supported by animal studies in which weight gain in a high fat diet model is prevented when GOAT is inhibited. Our objective was to determine whether botanicals demonstrating in vitro DGAT-1 and GOAT inhibition have similar mechanistic effects in the human body. Based on the results of this study, prototype formulas may be developed and clinically- tested for outcomes related to weight management.

Conditions

Overweight; Obesity

Outcome Measures

Primary Outcomes (2)

• Serum triglyceride response (area under the curve = AUC) following consumption of a standardized high fat meal challenge.

  Six hours

• Plasma acylated ghrelin response (AUC) following consumption of a standardized high fat meal challenge

  Three hours

Secondary Outcomes (4)

• Maximum concentration (Cmax) for serum triglycerides following consumption of a standardized high fat meal challenge

  Six hours

• Time to maximum concentration (Tmax) for serum triglycerides following consumption of a standardized high fat meal challenge

  Six hours

• Cmax for plasma acylated ghrelin following consumption of a standardized high fat meal challenge

  Three hours

• Tmax for plasma acylated ghrelin following consumption of a standardized high fat meal challenge

  Three hours

Study Arms (5)

Placebo

PLACEBO COMPARATOR

333 mg capsule comprised of silicified microcrystalline cellulose, magnesium stearate, modified cellulose gum, silicon dioxide, dextrose, corn starch, and caramel color. Consumed as six capsules once daily (total of 2 g/day) with the morning meal for a period of seven days.

Dietary Supplement: Placebo

Apple

EXPERIMENTAL

333 mg capsule comprised of apple peel extract (115:1, standardized to 80% polyphenol and 5% phlorizin). Consumed as six capsules once daily (total of 2 g/day) with the morning meal for a period of seven days.

Dietary Supplement: Apple

Grape

EXPERIMENTAL

333 mg capsule comprised of grape extract (8000:1, standardized to 75% total polyphenol, 50% oligomeric proanthocyanidin). Consumed as six capsules once daily (total of 2 g/day) with the morning meal for a period of seven days.

Dietary Supplement: Grape

Red Raspberry

EXPERIMENTAL

333 mg capsule comprised of red raspberry leaf extract (4:1, standardized to 6% ellagic acid). Consumed as six capsules once daily (total of 2 g/day) with the morning meal for a period of seven days.

Dietary Supplement: Raspberry

Apricot/Nectarine

EXPERIMENTAL

333 mg capsule comprised of apricot/nectarine extract (40:1, standardized to 50% polyphenol).

Dietary Supplement: Apricot/Nectarine

Interventions

Placebo DIETARY_SUPPLEMENT

Participants were randomly assigned to receive one of four botanical interventions or placebo.

Placebo

Apple DIETARY_SUPPLEMENT

Participants were randomly assigned to receive one of four botanical interventions or placebo.

Apple

Grape DIETARY_SUPPLEMENT

Participants were randomly assigned to receive one of four botanical interventions or placebo.

Grape

Raspberry DIETARY_SUPPLEMENT

Participants were randomly assigned to receive one of four botanical interventions or placebo.

Red Raspberry

Apricot/Nectarine DIETARY_SUPPLEMENT

Participants were randomly assigned to receive one of four botanical interventions or placebo.

Apricot/Nectarine

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Overweight/obese (BMI of 25-35 kg/m2) men and women.
• Participant must be 18-70 years of age.
• Considered healthy with no evidence of chronic diseases.
• Willing to maintain a consistent diet and exercise pattern throughout the duration of the study.
• Willing to consume a dairy and egg-based fat challenge meal twice, at start and end of study (V2 \& V3).

You may not qualify if:

• History of allergic reaction to fruit, dairy or egg products.
• Current smoker or history of tobacco use within the past year.
• Use of dietary supplements within 1 week prior to Visit 2 and unwilling to refrain from use through the duration of the trial. Supplements include any vitamins, minerals, and herbal products, including herbal drinks.
• Use of fish oil supplements within the past 8 weeks.
• Consumption of fatty fish one or more times per week within the past 8 weeks (e.g., mackerel, salmon, trout, canned albacore tuna, sardines, haddock, cod, hake, halibut, shrimp, sole, flounder, perch, black bass, swordfish, oysters, Alaskan king crab).
• Presence of cardiovascular disease, cancer, diabetes mellitus, inflammatory bowel disease, lactose intolerance, or any other chronic health condition identified from the findings of the interview.
• History of gastric bypass or other surgery that physically alters the gastrointestinal tract.
• Blood pressure greater \> 140 mm Hg systolic or \> 90 mm Hg diastolic during seated, resting measurement on two consecutive occasions during visit 1.
• Fasting serum triglycerides \> 200 mg/dl.
• Use of lipid lowering medications or dietary supplements.
• Use of blood pressure lowering medications or dietary supplements.
• Use of Coumadin, aspirin, or other medications that influence hemostasis.
• Daily use of low dose (\< 81 mg) aspirin is allowed.
• Use of antibiotics within the past week.
• Chronic or therapeutic use of antacids, H2 agonists, and proton pump inhibitors.

Sponsors & Collaborators

• Access Business Group: lead
• Radiant Research: collaborator

Related Publications (1)

• Velliquette RA, Grann K, Missler SR, Patterson J, Hu C, Gellenbeck KW, Scholten JD, Randolph RK. Identification of a botanical inhibitor of intestinal diacylglyceride acyltransferase 1 activity via in vitro screening and a parallel, randomized, blinded, placebo-controlled clinical trial. Nutr Metab (Lond). 2015 Aug 6;12:27. doi: 10.1186/s12986-015-0025-2. eCollection 2015.

  PMID: 26246845 DERIVED

MeSH Terms

Conditions

Overweight; Obesity

Interventions

whole grape extract; Prunus armeniaca extract

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2015
• First Posted: January 7, 2015
• Study Start: May 1, 2012
• Primary Completion: August 1, 2012
• Study Completion: August 1, 2012
• Last Updated: January 7, 2015

Record last verified: 2015-01