30 Participants Needed

Arginine Metabolism Study for Youth with Type 2 Diabetes

LM
MT
Overseen ByMustafa Tosur, MD
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

Will I have to stop taking my current medications?

You may need to stop taking certain medications if they interfere with amino acid metabolism or if you are on hormonal replacement therapy. However, you can continue taking metformin, insulin, and liraglutide.

What data supports the effectiveness of the drug for youth with Type 2 Diabetes?

Research shows that L-arginine can help restore endothelial function (the inner lining of blood vessels) in diabetes, which is important for heart health. Additionally, L-arginine has been shown to improve insulin sensitivity, which is beneficial for managing Type 2 Diabetes.12345

Is the use of stable isotopes, including L-arginine, safe in humans?

Stable isotopes, which include forms like L-arginine, have been used safely in humans for over fifty years. They are not radioactive and have no known side effects when used in small amounts.26789

How is the Arginine Metabolism Study treatment different from other treatments for Type 2 Diabetes?

This treatment is unique because it uses a combination of intravenous arginine, oral glucose, and stable isotope infusion to study arginine metabolism, which is not a standard approach for managing Type 2 Diabetes. It focuses on understanding metabolic pathways rather than directly controlling blood sugar levels, which is the goal of most traditional diabetes treatments.910111213

What is the purpose of this trial?

Type 2 diabetes (T2D), once considered only "a disease of older ages," is now a significant public health concern in youth. Although it is characterized by insulin resistance and impaired insulin secretion, its precise etiology and pathogenesis are not yet fully understood. This study aims to (1) explore arginine metabolism in youth with T2D via safe, minimally invasive kinetic experiments using stable isotope tracers and targeted metabolomics, and (2) determine the effect of exogenous arginine administration on β-cell function in youth with T2D, potentially supporting the use of this safe, low-cost, and readily available nutrient to improve pediatric diabetes outcomes.

Research Team

MT

Mustafa Tosur, MD

Principal Investigator

Baylor College of Medicine

Eligibility Criteria

This trial is for young people with Type 2 Diabetes, aged 12-20 years. Girls must be postmenarchal and boys at Tanner stage 5 genitalia. Participants should have been diagnosed with T2D for 3 months to 10 years. Those on hormonal therapy, insulin, or certain medications, or with other health issues like abnormal liver function or pregnancy cannot join.

Inclusion Criteria

I am a young person with type 2 diabetes.
I am a girl aged 12-20 years postmenarchal or a boy aged 14-20 years at Tanner stage 5.
I am a young person with Type 2 Diabetes for 3 months to 10 years.

Exclusion Criteria

Your diabetes is not well controlled, with HbA1c higher than 8%.
I am not on medications that affect amino acid metabolism.
My kidney function is reduced with an eGFR below 90 mL/min/1.73 m2.
See 6 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Study Day 1

Participants receive a primed dose of stable isotopes followed by continuous intravenous infusions for 5 hours

1 day
1 visit (in-person)

Study Day 2

Participants undergo an oral glucose tolerance test after drinking a 75-gram glucose solution

1 day
1 visit (in-person)

Study Day 3

Participants undergo a modified oral glucose tolerance test with a 75-gram glucose solution and a 5-gram arginine injection

1 day
1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the study procedures

4 weeks

Treatment Details

Interventions

  • Intravenous arginine bolus
  • Oral glucose ingestion
  • Stable isotope infusion
Trial Overview The study investigates how the body processes arginine in youths with Type 2 Diabetes by using stable isotope tracers and oral glucose tests. It also examines if taking extra arginine can help improve the function of cells that make insulin.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: The study cohort consisting of youth with type 2 diabetes and healthy controlsExperimental Treatment1 Intervention
In Study Day 1, participants will be given a primed dose of stable isotopes followed by continuous intravenous infusions for 5 hours. The investigators will use the following isotopes: U-13C6-Arg, 5,5-2H2-Cit, 15N2-Orn, 2H5-Phe, and Na13CO3. On Study Day 2, participants will drink a 75-gram glucose solution prior to an oral glucose tolerance test. On Study Day 3, participants will drink a 75-gram glucose solution and will be injected 5-gram arginine into their veins.

Intravenous arginine bolus is already approved in United States, European Union for the following indications:

🇺🇸
Approved in United States as L-arginine for:
  • Nutritional supplement
  • Pharmaceutical aid
🇪🇺
Approved in European Union as L-arginine for:
  • Nutritional supplement
  • Pharmaceutical aid

Find a Clinic Near You

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials
1,044
Recruited
6,031,000+

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

Collaborator

Trials
2,513
Recruited
4,366,000+

Findings from Research

In experimental diabetes mellitus, there is a shift in L-arginine metabolism towards increased arginase activity, which reduces the availability of free L-arginine and affects nitric oxide production.
Long-term infusion of L-arginine can restore endothelial function in diabetic conditions, but this effect diminishes once the infusion stops, indicating a temporary benefit.
[Effect of L-arginine on the endothelium functional activity in experimental diabetes mellitus].Sahach, VF., Prysiazhna, OD., Tkachenko, MN., et al.[2014]
A new protocol using stable isotope tracers after an oral glucose challenge provides more accurate estimates of glucose effectiveness and insulin sensitivity compared to traditional methods, with values 2-3 times higher than those from frequently sampled intravenous glucose tolerance tests.
The study, involving six healthy adults tested twice, demonstrated that the two-compartment model for glucose distribution offers a better physiological understanding of glucose kinetics, and the insulin sensitivity measurements showed high reproducibility with a 93% correlation between tests.
A stable isotope minimal model protocol with oral glucose administration.Bluck, LJ., Clapperton, AT., Coward, WA.[2022]
In a study involving 17 healthy young adults, oral L-citrulline supplementation did not improve treadmill time to exhaustion; in fact, it resulted in a shorter time compared to a placebo, suggesting it may not enhance exercise performance as expected.
Additionally, L-citrulline ingestion was associated with a lack of the normal increase in plasma insulin levels following high-intensity exercise, indicating it may affect insulin secretion or clearance during physical activity.
L-citrulline reduces time to exhaustion and insulin response to a graded exercise test.Hickner, RC., Tanner, CJ., Evans, CA., et al.[2013]

References

[Effect of L-arginine on the endothelium functional activity in experimental diabetes mellitus]. [2014]
A stable isotope minimal model protocol with oral glucose administration. [2022]
L-citrulline reduces time to exhaustion and insulin response to a graded exercise test. [2013]
Assessment of insulin action in insulin-dependent diabetes mellitus using [6(14)C]glucose, [3(3)H]glucose, and [2(3)H]glucose. Differences in the apparent pattern of insulin resistance depending on the isotope used. [2018]
L-arginine-nitric oxide kinetics in normal and type 2 diabetic subjects: a stable-labelled 15N arginine approach. [2019]
Stable isotopes in biosciences, their measurement and models for amino acid metabolism. [2019]
Use of stable isotopes to assess protein and amino acid metabolism in children and adolescents: a brief review. [2013]
Evidence for separate handling in vivo of different regions of the insulin molecule using A14- and B1-labeled insulin tracers. [2019]
Quantifying rates of glucose production in vivo following an intraperitoneal tracer bolus. [2018]
10.United Statespubmed.ncbi.nlm.nih.gov
Determination of a glucose-dependent futile recycling rate constant from an intraperitoneal glucose tolerance test. [2019]
11.United Statespubmed.ncbi.nlm.nih.gov
Capillary Electrophoresis-High Resolution Mass Spectrometry for Measuring In Vivo Arginine Isotope Incorporation in Alzheimer's Disease Mouse Models. [2021]
12.United Statespubmed.ncbi.nlm.nih.gov
Dietary arginine uptake by the splanchnic region in adult humans. [2017]
13.United Statespubmed.ncbi.nlm.nih.gov
Relation between insulin and glucose flux rates in the dog. [2015]
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