Clinical trial NCT06790771: Effect of Supplement on Appetite and GLP-1
Official title: Acute Effect of Supplement Containing L-Arginine on Appetite Suppression and GLP-1 Induction
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Hunger
Keywords: Hunger
GLP-1
Satiety
Supplement
Lead sponsor: Texas Christian University
Sponsor class: OTHER
Collaborators: name: Healthrite Partners
name: GMT Nutrition, LLC
First posted: 2025-01-24
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Each participant will undergo the three experimental conditions in random order. Each intervention will be separated by a wash out period of 1 week.
Primary purpose: PREVENTION

Brief summary: Study Summary

The goal of this study is to understand whether a dietary supplement containing L-arginine, resveratrol, tart cherry, and vitamin C reduces hunger and increases the release of GLP-1, a hormone associated with appetite suppression and improved glucose regulation. The study will also explore the metabolic effects of the supplement.

Main Questions:

1. Does the supplement reduce hunger more effectively than a placebo?
2. Does it enhance GLP-1 release in individuals with overweight or obesity?

Participants:

* Age: 18-60 years
* Body Mass Index (BMI): 25-40 kg/m²
* Total participants: 25
* Must maintain usual eating and activity habits during the study.

Study Design:

* Conditions Tested: High-dose supplement, low-dose supplement, and placebo.
* Participants will undergo three separate 2-hour lab visits, each after fasting for 8 hours.
* During each visit:
* Consume the assigned supplement or placebo.
* Eat a standardized meal after a 60-minute rest.
* Provide blood samples at eight time points to measure GLP-1 and other metabolic markers.
* Rate hunger using a 7-point scale.

Benefits and Risks:

* Benefits: Participants may not directly benefit, but the findings could lead to new appetite-suppressing supplements that aid in weight loss.
* Risks: Include discomfort from blood draws, possible gastrointestinal side effects from the supplement, and allergic reactions. Measures are in place to minimize these risks, such as pre-screening for allergies and using trained personnel for blood collection.

This study is triple-blinded, meaning neither the participants, researchers, nor analysts will know which condition is being tested during each visit. Data collected will be anonymized to protect participant privacy.

Detailed description: Study Title:

Acute Effect of Supplement Containing L-Arginine on Appetite Suppression and GLP-1 Induction

Research Objectives:

The study aims to evaluate the effects of a dietary supplement containing L-arginine, resveratrol, tart cherry, and vitamin C on appetite suppression, GLP-1 hormone release, and associated metabolic outcomes in individuals with overweight or obesity.

Background:

GLP-1 (Glucagon-Like Peptide 1) plays a crucial role in regulating appetite and glucose homeostasis.

Condensed Background Information:

The combination of the following ingredients is hypothesized to have a synergistic effect, promoting satiety and improving metabolic health:

* L-arginine enhances GLP-1 secretion, improving glucose tolerance and reducing appetite.
* Resveratrol inhibits DPP-IV, extending the activity of GLP-1.
* Tart cherry supports metabolic regulation by enhancing nitric oxide availability and preventing arginine catabolism.
* Vitamin C acts as an antioxidant, supporting the efficacy of other components.

Participant Details:

* Number of Participants: 25
* Eligibility Criteria:
* Adults aged 18-60 years.
* BMI between 25 and 40 kg/m².
* Must maintain current diet and physical activity levels.

Exclusion Criteria:

* Significant weight change (\>5%) in the last three months.
* Medical conditions like uncontrolled diabetes, kidney disease, thyroid disorders, or autoimmune diseases.
* Current use of medications or supplements affecting weight or GLP-1 levels.
* Pregnancy or lactation.

Study Design:

This is a randomized, triple-blinded, placebo-controlled study with three conditions:

* High-Dose Supplement (\~10 g)
* Low-Dose Supplement (\~5 g)
* Placebo (\~5 g) Each participant will experience all three conditions in random order.

The timeline for the study involves:

* Pre-Session: 8-hour fasting before each visit.
* Arrival at the lab (Rickel Building, Rooms 256/259).
* Baseline blood sample collection.
* Administration of assigned supplement/placebo.
* 60-minute rest period.
* Consumption of a standardized meal (Bertolli Chicken Alfredo pasta bake) in isolation within a 30-minute window.
* Collection of additional blood samples at eight-time points
* Measurement of hunger using a 7-point scale.

Study Procedures

Blood Sampling:

* 7 mL samples collected at each time point for metabolic analysis (e.g., glucose, insulin, GLP-1).
* Total blood volume: 168 mL per participant across all sessions.
* Samples will be analyzed for metabolic markers in Dr. Ryan Porter's lab.

Satiety Measurement:

Participants will rate hunger levels at each blood draw using a scale from "Extremely Hungry" to "Extremely Full."

Meal Intake:

An ad libitum meal is provided to assess the impact of supplementation on food consumption.

Risks and Mitigation

* Blood Draw Risks: Bruising, pain, infection, or dizziness. Managed by using trained personnel and aseptic techniques.
* Supplement Risks: Gastrointestinal discomfort and allergic reactions. Addressed by pre-screening participants for allergies. Emergency supplies will be available.
* Data Privacy Risks:

All data will be anonymized and stored securely to prevent breaches.

Expected Outcomes

The study aims to determine:

* If the supplement reduces hunger compared to a placebo.
* If it enhances GLP-1 release post-meal.
* If it improves other metabolic parameters (e.g., glucose, lipid profiles).

Data Handling:

All data will be anonymized and securely stored. Samples may be retained for up to 24 months for further research.

Statistical Analysis:

Data analysis will use ANOVA and Tukey's post-hoc tests in SPSS, with significance set at p\<0.05.

Study Impact:

This research could contribute to developing effective nutritional interventions to support appetite regulation and weight management, benefiting individuals with obesity and/or metabolic disorders.

Eligibility criteria: Inclusion Criteria:

Participants must meet all the following conditions to be eligible for the study:

* Age: 18-60 years old.
* BMI (Body Mass Index): Between 25 and 40 kg/m².
* Diet and Activity Stability: Willing to maintain current dietary and physical activity habits for the duration of the study.

Exclusion Criteria:

Participants will be excluded from the study if any of the following conditions apply:

* Recent Weight Change: Lost or gained more than 5% of body weight in the last 3 months.
* Pregnancy or Lactation: Pregnant or breastfeeding women.
* Medical Conditions:

  * Kidney disease (Chronic Kidney Disease or End-Stage Renal Disease).
  * Herpes simplex.
  * Uncontrolled diabetes (HbA1c \>7%).
  * Thyroid disorders or taking thyroid medications.
  * Type 1 diabetes.
  * Cushing syndrome.
  * Cirrhosis or hepatitis.
  * Chronic obstructive pulmonary disease (COPD).
  * Dementias.
  * Active autoimmune diseases (e.g., lupus, rheumatoid arthritis).
  * Crohn's disease or ulcerative colitis.
  * Celiac disease.
  * Allergies or Sensitivities:
  * Known allergies to any components of the supplement or standardized meal.
  * Medications: Currently taking any of the following:
* Supplements or medications for weight loss.
* Antihypertensive, antidiabetic, or antihyperlipidemic medications.
* Erectile dysfunction medications.
* Blood thinners (e.g., aspirin, warfarin).
* Medications containing nitric oxide or nitroglycerin.
* Drugs affecting GLP-1 levels, such as GLP-1 receptor agonists, insulin, certain antidepressants, or corticosteroids.

  * Substance Use: Evidence of illegal drug use, including marijuana.
  * Participation in Other Studies: Enrollment in another clinical trial that could interfere with the study outcomes.

Primary outcomes:
measure: Appetite
timeFrame: 2 hours per session, measured during three separate sessions over three weeks.
measure: Food Intake
timeFrame: Single meal during each session, measured in three sessions over three weeks.
measure: Blood Glucose
timeFrame: 2 hours per session, measured during three separate sessions over three weeks.
Secondary outcomes:
measure: Insulin Levels
timeFrame: 2 hours per session, measured during three separate sessions over three weeks.
measure: Lipid Profile Levels
timeFrame: 2 hours per session, measured during three separate sessions over three weeks.
Other outcomes:
Locations:
city: Fort Worth
country: United States
facility: Texas Christian University
state: Texas
Study officials:
References:
citation: Lucotti P, Setola E, Monti LD, Galluccio E, Costa S, Sandoli EP, Fermo I, Rabaiotti G, Gatti R, Piatti P. Beneficial effects of a long-term oral L-arginine treatment added to a hypocaloric diet and exercise training program in obese, insulin-resistant type 2 diabetic patients. Am J Physiol Endocrinol Metab. 2006 Nov;291(5):E906-12. doi: 10.1152/ajpendo.00002.2006. Epub 2006 Jun 13.
citation: Dashtabi A, Mazloom Z, Fararouei M, Hejazi N. Oral L-Arginine Administration Improves Anthropometric and Biochemical Indices Associated With Cardiovascular Diseases in Obese Patients: A Randomized, Single Blind Placebo Controlled Clinical Trial. Res Cardiovasc Med. 2015 Dec 29;5(1):e29419. doi: 10.5812/cardiovascmed.29419. eCollection 2016 Feb.
citation: Rogers DR, Lawlor DJ, Moeller JL. Vitamin C Supplementation and Athletic Performance: A Review. Curr Sports Med Rep. 2023 Jul 1;22(7):255-259. doi: 10.1249/JSR.0000000000001083.
citation: Ceriello A, Novials A, Ortega E, Canivell S, Pujadas G, La Sala L, Bucciarelli L, Rondinelli M, Genovese S. Vitamin C further improves the protective effect of GLP-1 on the ischemia-reperfusion-like effect induced by hyperglycemia post-hypoglycemia in type 1 diabetes. Cardiovasc Diabetol. 2013 Jun 27;12:97. doi: 10.1186/1475-2840-12-97.
citation: Hooper DR, Orange T, Gruber MT, Darakjian AA, Conway KL, Hausenblas HA. Broad Spectrum Polyphenol Supplementation from Tart Cherry Extract on Markers of Recovery from Intense Resistance Exercise. J Int Soc Sports Nutr. 2021 Jun 14;18(1):47. doi: 10.1186/s12970-021-00449-x.
citation: Bordage S, Pham TN, Zedet A, Gugglielmetti AS, Nappey M, Demougeot C, Girard-Thernier C. Investigation of Mammal Arginase Inhibitory Properties of Natural Ubiquitous Polyphenols by Using an Optimized Colorimetric Microplate Assay. Planta Med. 2017 May;83(7):647-653. doi: 10.1055/s-0042-118711. Epub 2016 Oct 24.
citation: Kim DW, Jung DH, Sung J, Min IS, Lee SJ. Tart Cherry Extract Containing Chlorogenic Acid, Quercetin, and Kaempferol Inhibits the Mitochondrial Apoptotic Cell Death Elicited by Airborne PM10 in Human Epidermal Keratinocytes. Antioxidants (Basel). 2021 Mar 13;10(3):443. doi: 10.3390/antiox10030443.
citation: Huang PK, Lin SR, Chang CH, Tsai MJ, Lee DN, Weng CF. Natural phenolic compounds potentiate hypoglycemia via inhibition of Dipeptidyl peptidase IV. Sci Rep. 2019 Oct 30;9(1):15585. doi: 10.1038/s41598-019-52088-7.
citation: Hurt RT, Ebbert JO, Schroeder DR, Croghan IT, Bauer BA, McClave SA, Miles JM, McClain CJ. L-arginine for the treatment of centrally obese subjects: a pilot study. J Diet Suppl. 2014 Mar;11(1):40-52. doi: 10.3109/19390211.2013.859216. Epub 2014 Jan 10.
citation: Amin A, Neophytou C, Thein S, Martin NM, Alamshah A, Spreckley E, Bloom SR, Murphy KG. L-Arginine Increases Postprandial Circulating GLP-1 and PYY Levels in Humans. Obesity (Silver Spring). 2018 Nov;26(11):1721-1726. doi: 10.1002/oby.22323.
citation: Clemmensen C, Smajilovic S, Smith EP, Woods SC, Brauner-Osborne H, Seeley RJ, D'Alessio DA, Ryan KK. Oral L-arginine stimulates GLP-1 secretion to improve glucose tolerance in male mice. Endocrinology. 2013 Nov;154(11):3978-83. doi: 10.1210/en.2013-1529. Epub 2013 Aug 19.