Glutamine Metabolism Assessment in Healthy Subjects

Overseen By Wilson Gonsalves

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Mayo Clinic

Must not be taking: Steroids

Disqualifiers: Renal failure, Pregnancy, Liver disease, Anemia, Alcohol use, others

Compensation: Varies

Number of Visits: 2

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how the body uses a nutrient called glutamine, focusing on healthy bone marrow cells. Researchers are testing two methods: one administers a special form of glutamine (5-13C-Glutamine) through an IV before taking a bone marrow sample, and the other examines the sample in a lab setting. The goal is to determine which method better reveals how the body uses glutamine. The trial seeks healthy participants without kidney or liver problems, who are not anemic, and have a BMI of 30 or less. As an unphased trial, this study offers a unique opportunity to contribute to foundational research on nutrient utilization in the body.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are using steroids.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that L-Glutamine is generally safe and well-tolerated by the body. As a common amino acid naturally found throughout the body, it is something the body already uses daily. However, some reports mention minor side effects like eye or skin irritation.

In some cases, when taken as an oral powder, L-Glutamine has been associated with an overactive spleen, stomach pain, and mild discomforts such as a burning sensation or hot flashes. These side effects are rare and usually not serious.

Since this study uses a special form of L-Glutamine called 5-13C-Glutamine, discussing any concerns with the study team is important. Overall, evidence suggests that the treatment is safe for humans, especially since L-Glutamine is FDA-approved for other uses. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores how the body processes glutamine, an important amino acid, which could unlock new insights into metabolism. Unlike typical metabolic studies that may focus on dietary intake or enzyme activity, this trial uses 5-13C-Glutamine, a special labeled version of glutamine that allows scientists to trace its path through the body with precision. Additionally, the trial employs both in vivo and ex vivo approaches, offering a comprehensive view by examining glutamine metabolism inside the body and in cultured plasma cells. Understanding these mechanisms in healthy subjects may pave the way for breakthroughs in treating metabolic disorders or cancer.

What evidence suggests that this trial's treatments could be effective for assessing glutamine metabolism?

This trial will assess glutamine metabolism using a special form of glutamine, called 5-13C-Glutamine, to observe how the body uses this amino acid. In one arm of the trial, healthy subjects receive an intravenous infusion of 5-13C-Glutamine before undergoing a bone marrow aspiration. In another arm, plasma cells obtained from bone marrow aspiration are cultured ex vivo in cell culture media containing 5-13C-Glutamine. Studies have shown that glutamine is crucial for various body functions, such as supporting immune cell growth and infection defense. By studying this special glutamine, researchers aim to better understand its role in healthy cells, potentially leading to improved methods for supporting cell function and health. ^{4 6 7 8 9}

Who Is on the Research Team?

Wilson Gonsalves, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for healthy adults aged 18-60 who can give written consent. It's not suitable for pregnant individuals, those with liver disease, kidney failure, anemia (low hemoglobin levels), heavy alcohol users (>2 drinks per day), people with a BMI over 30, or anyone currently using steroids.

Inclusion Criteria

Able to provide written consent

Exclusion Criteria

Pregnancy

Anemia (Hemoglobin < 12.5 g/dL in men and < 11.5 g/dL in women)

History of alcohol use (average > 2 drinks per day)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

In Vivo Assessment

Infusion of 5-13C-Glutamine intravenously in healthy subjects prior to undergoing a bone marrow aspiration

1 day

1 visit (in-person)

Ex Vivo Assessment

Bone marrow aspiration followed by ex vivo culture of plasma cells in media containing 5-13C-Glutamine

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the assessments

1 week

What Are the Treatments Tested in This Trial?

Interventions

• 5-13C-Glutamine
• Bone marrow aspiration

Trial Overview The study is testing how bone marrow plasma cells in healthy subjects use glutamine. Participants will undergo a bone marrow aspiration and receive a special form of glutamine labeled with carbon-13 to track its utilization in the body compared to lab-based tests.

How Is the Trial Designed?

Group I: In Vivo Experimental Treatment 2 Interventions

Infusion of 5-13C-Glutamine intravenously in healthy subjects prior to undergoing a bone marrow aspiration.

Group II: Ex Vivo Placebo Group 1 Intervention

Healthy subjects will undergoing a bone marrow aspiration and then the plasma cells acquired will be cultured ex vivo in cell culture media containing 5-13C-Glutamine.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Published Research Related to This Trial

A new automated method for producing the radiotracer [11C]Gln was developed, yielding over 3.7 GBq of product with over 99% radiochemical purity, making it suitable for human use.

This production process is efficient, taking about 45 minutes, and ensures a chemically pure final product, which is crucial for its application in cancer research and diagnostics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Automated radiosynthesis of 5-[11C]l-glutamine, an important tracer for glutamine utilization. Rosenberg, AJ., Nickels, ML., Schulte, ML., et al.[2020]

The first-in-human study of the PET tracer 11C-glutamine in nine patients with metastatic colorectal cancer showed it was well tolerated with no safety concerns, indicating its potential for safe use in cancer imaging.

11C-glutamine effectively visualized metastatic lesions in organs such as the lung, brain, bone, and liver, suggesting its utility for noninvasive imaging and monitoring of cancer treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-Human PET Imaging and Estimated Radiation Dosimetry of l-[5-11C]-Glutamine in Patients with Metastatic Colorectal Cancer. Cohen, AS., Grudzinski, J., Smith, GT., et al.[2023]

In a study involving healthy young adult males, intravenous infusions of labeled glutamate and glutamine showed that the turnover rates for these amino acids are quite fast, with glutamate at 8.0% min-1 and glutamine at 2.8% min-1, indicating rapid metabolism.

The research revealed that only a small fraction (5%) of plasma glutamine comes from intracellular glutamate, suggesting that the kinetics measured reflect transport through plasma rather than overall body metabolism, highlighting the complexity of amino acid dynamics in the body.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glutamine and glutamate kinetics in humans. Darmaun, D., Matthews, DE., Bier, DM.[2017]

In a study comparing six severely burned men to five healthy men, it was found that both groups had increased whole-body glutamine flux in response to stress, but the severely burned patients showed a decreased rate of glutamine release from muscles, indicating a compromised response to injury.

The results suggest that during severe injury, the body struggles to produce enough glutamine, making it a conditionally essential amino acid in critical illness, as the muscles fail to enhance its synthesis when reserves are low.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glutamine kinetics in burn patients. Comparison with hormonally induced stress in volunteers. Gore, DC., Jahoor, F.[2019]

Glutamine supplementation is showing promise as a beneficial adjunct therapy for patients undergoing bone marrow transplantation (BMT), helping to combat protein wasting, gut injury, and immune system issues after high-dose chemotherapy.

Current studies suggest that glutamine is well tolerated and may improve outcomes in stressed patients, but more rigorous randomized controlled trials are needed to fully establish its efficacy in modern BMT protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glutamine supplementation in bone marrow transplantation. Ziegler, TR.[2019]

Glutamine supplementation in animal models has shown potential benefits in cancer treatment, such as tumor regression and improved immune response, despite initial concerns about promoting tumor growth.

In human studies, glutamine may help reduce mucositis and graft versus host disease in bone marrow transplantation, but results are inconsistent and more high-quality research is needed to confirm its efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hot topics in parenteral nutrition. A review of the use of glutamine supplementation in the nutritional support of patients undergoing bone-marrow transplantation and traditional cancer therapy. Crowther, M.[2021]

A new method using gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS) allows for precise measurement of low levels of 13C-labeled glutamine in plasma, improving the ability to study glutamine metabolism in vivo.

This technique can measure 13C enrichments as low as 0.06 mol.% with high precision, making it a valuable tool for understanding glutamine's role as a fuel for rapidly dividing cells, such as those in the gut and immune system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determination of low 13C-glutamine enrichments using gas chromatography-combustion-isotope ratio mass spectrometry. Menand, C., Pouteau, E., Marchini, S., et al.[2013]

L-Glutamine was found to be safe in various tests, showing no mutagenic effects or chromosomal damage in laboratory assays, indicating it does not pose genetic risks.

In a 13-week study with Sprague-Dawley rats, even at the highest tested concentration of 5.0% in their diet, there were no significant adverse effects on health, suggesting a high safety margin for L-glutamine supplementation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral subchronic and genotoxicity studies conducted with the amino acid, L-glutamine. Wong, AW., Magnuson, BA., Nakagawa, K., et al.[2013]

Glutamine supplementation, whether given through the gut or intravenously, has been found to be safe and effective for patients undergoing bone marrow transplantation, helping to mitigate the severe side effects of high-dose chemotherapy and total body irradiation.

There is a need for further double-blind controlled clinical trials to explore the benefits of glutamine in the context of modern treatment regimens that include new combinations of chemotherapy and growth factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glutamine in the support of patients following bone marrow transplantation. Wilmore, DW., Schloerb, PR., Ziegler, TR.[2019]

The automated synthesis of the PET radiotracer [11C]L-glutamine was successfully developed, yielding a high radiochemical purity of over 90% and a yield of 43-52%, making it reliable for imaging metabolic pathways in cancers like triple negative breast cancer.

This synthesis process can be easily adapted for clinical research, providing a valuable tool for studying tumor biology and the role of L-glutamine in cancer metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Automated synthesis of [11C]L-glutamine on Synthra HCN plus synthesis module. Padakanti, PK., Li, S., Schmitz, A., et al.[2020]

Exogenous glutamine infusion significantly increases plasma glutamine levels and its appearance rate in the body, indicating enhanced glutamine metabolism, as shown in a study with six healthy men.

The study found that while glutamine infusion raised oxidation rates and plasma concentrations, it decreased the body's own production of glutamine, suggesting that external glutamine can influence internal metabolic processes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Response of glutamine metabolism to exogenous glutamine in humans. Hankard, RG., Darmaun, D., Sager, BK., et al.[2017]

In a study involving 10 normal postabsorptive volunteers, the turnover rates of plasma glutamine were found to differ significantly based on the tracer used, with [3,4-3H]glutamine showing the highest turnover rate, indicating that the choice of tracer can impact the measurement of glutamine metabolism.

The study validated monocompartmental equations for estimating plasma glutamine turnover under non-steady-state conditions, demonstrating that these equations can provide accurate predictions with minimal deviations, which is important for understanding glutamine dynamics in metabolic studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Steady-state and non-steady-state measurements of plasma glutamine turnover in humans. Kreider, ME., Stumvoll, M., Meyer, C., et al.[2017]

Citations

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Glutamine: Metabolism and Immune Function ... Glutamine is an essential nutrient for lymphocyte proliferation and cytokine production, macrophage phagocytic plus secretory activities, and neutrophil ...

2. medchemexpress.com medchemexpress.com/l-glutamine-5-13c.html?srsltid=AfmBOopReADD3VeeKkIEwVQikSF-yZ4lQuGDqhMS6vEBnplygAW3OqRZ

L-Glutamine-5- 13 C (Synonyms: L-Glutamic acid 5-amide-5 L-Glutamine-5-13C is the 13C-labeled L-Glutamine. L-Glutamine (L-Glutamic acid 5-amide) is a non-essential amino acid present abundantly throughout the body ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1319016413000029

Review Glutamic acid as anticancer agent: An overview The objective of the article is to highlight various roles of glutamic acid like endogenic anticancer agent, conjugates to anticancer agents, and derivatives ...

4. isotope.com isotope.com/metabolomics-and-cellular-metabolism/l-glutamine-13c5-clm-1822-h-01

L-Glutamine (¹³C₅, 99%) L-Glutamine (13C5) is a canonical amino acid that is used as a quantitative standard or metabolic tracer in MS-based experiments.

5. pubchem.ncbi.nlm.nih.gov pubchem.ncbi.nlm.nih.gov/compound/L-Glutamine

L-Glutamine | C5H10N2O3 | CID 5961 - PubChem A non-essential amino acid present abundantly throughout the body and is involved in many metabolic processes. It is synthesized from glutamic acid and ammonia.

6. isotope.com isotope.com/product/attachment/CDNLM-6805-PK/SDS%20-%20CDNLM-6805.pdf

L-GLUTAMINE (13C5, 97-99% Consult a physician and show this safety data sheet. First-aid measures after inhalation. : If breathed in, move person to fresh air. If not ...

7. medchemexpress.com medchemexpress.com/l-glutamine-5-13c.html?srsltid=AfmBOopnHavCo95BO6U2BvaA9kTk8mzH6v8PvlqjK6QQtU4SDBc8O6EI

L-Glutamine-5- 13 C (Synonyms: L-Glutamic acid 5-amide-5 L-Glutamine-5-13C is the 13C-labeled L-Glutamine. L-Glutamine (L-Glutamic acid 5-amide) is a non-essential amino acid present abundantly throughout the body ...

8. spectrumchemical.com spectrumchemical.com/media/sds/GL136_AGHS.pdf?srsltid=AfmBOop3yvxU2B7-YkIXbyue8lqJtk8oYU5GZsyJcseaXm6yXNX3otwe

C:\Program Files\WERCS50\DOCS\wercs.ps Consult a physician if necessary. Most important symptoms and effects, both acute and delayed. Symptoms. May cause eye/skin irritation.

9. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2017/208587s000lbl.pdf

ENDARI (L-glutamine oral powder ) - accessdata.fda.gov These adverse reactions included one case each of hypersplenism, abdominal pain, dyspepsia, burning sensation, and hot flash. Serious adverse reactions were ...