Glycolate Metabolism Study in Healthy Subjects

Overseen By Sonia Fargue, M.D., Ph.D.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Alabama at Birmingham

Disqualifiers: Hepatic, renal, bowel, endocrine, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how the body processes glycolate, a compound related to oxalate that can contribute to kidney stones, using a special carbon tracer. Participants will follow a controlled diet and receive one of three treatments: a constant infusion of 13C2-Glycolate (a labeled form of glycolate), a single oral dose, or a single intravenous dose. The study seeks healthy adults who can commit to dietary rules and urine collection. As an unphased trial, it offers participants the opportunity to contribute to foundational research that could lead to better understanding and treatment of kidney stones.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, since the study involves healthy subjects, it's possible that any medications affecting metabolism might need to be paused. Please consult with the study coordinators for specific guidance.

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

Research has shown that glycolic acid, the main ingredient in the treatments under study, is generally safe when used in controlled environments. Studies on the continuous infusion of 13C2-Glycolate have found no harmful effects at certain inhaled levels, indicating it is well-tolerated.

For the single oral dose, evidence suggests that very high doses of similar substances can cause issues, such as metabolism problems and potential kidney concerns. However, these effects appeared only at doses much higher than those typically used in studies.

Research has used the single intravenous dose of 13C2-glycolate without significant problems. This dose helps researchers understand how the body processes the substance and is not at levels known to cause harm.

Overall, glycolic acid has been studied for various uses, and when used in controlled amounts, it is generally considered safe. The study uses doses that are low and safe, based on previous research. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it aims to explore how 13C2-Glycolate is metabolized in the body, offering new insights into glycolate metabolism. Unlike other studies that may focus on disease states, this trial involves healthy subjects to establish a baseline understanding. The unique aspect of this trial is its use of carbon-13 labeled glycolate, which allows for precise tracking of the compound's metabolic pathway. By examining different administration methods—constant infusion, single oral dose, and single intravenous dose—the trial can provide comprehensive data on how the body processes glycolate, potentially leading to new approaches in treating conditions related to its metabolism.

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

This trial will study the metabolism of glycolate using a special form called 13C2-glycolate. Participants will be assigned to different treatment arms, each involving a unique method of administering 13C2-glycolate. Research has shown that glycolate plays an important role in how the body handles oxalate, a substance that can cause kidney stones. Studies have found that glycolate converts into glyoxylate and then into oxalate in the body. By using 13C2-glycolate, researchers can track how glycolate breaks down, helping them understand its effect on oxalate levels in urine. Early results suggest that understanding this process could help control oxalate levels and possibly lower the risk of kidney stones. More research is needed to confirm these findings, but this is a promising area of study for those interested in kidney health. ^{2 6 7 8 9}

Who Is on the Research Team?

Sonia Fargue, M.D., Ph.D.

Principal Investigator

University of Alabama at Birmingham

Are You a Good Fit for This Trial?

This trial is for mentally competent adults aged 18-75, with a BMI between 19 and 40, who are in good health as determined by medical history and blood tests. They must have completed acceptable urine collections twice for screening. It's not for pregnant or lactating individuals, those planning to become pregnant soon, or anyone with liver, kidney, bowel or endocrine diseases.

Inclusion Criteria

I am in good health based on my medical history and recent blood tests.

Your body mass index (BMI) falls within the range of 19 to 40.

I can understand and make decisions about my health care.

Exclusion Criteria

Pregnancy, intention to become pregnant in the near future, or lactation

I have a condition that could affect how my body absorbs or gets rid of substances.

Abnormal urine chemistries or blood metabolic profiles

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Dietary Control

Participants consume a controlled low-oxalate diet for 5 days to equilibrate before glycolate administration.

5 days

No visits required

Glycolate Administration and Monitoring

Participants receive either a constant infusion, single oral dose, or single intravenous dose of carbon-13 glycolate. Blood and urine samples are collected to measure labeled glycolate and oxalate.

1 day

1 visit (in-person) lasting 7-10 hours

Follow-up

Participants are monitored for safety and effectiveness after glycolate administration, with continued urine collection at home.

1 day

No additional visits required

What Are the Treatments Tested in This Trial?

Interventions

• 13C2-Glycolate
• Low oxalate controlled Diet

Trial Overview

The study is testing how the body processes a substance called glycolate into another substance called oxalate using different methods: an IV infusion, an oral dose of labeled glycolate (13C2-Glycolate), and while on a low-oxalate diet. The goal is to understand how this metabolism contributes to the amount of oxalate in urine.

How Is the Trial Designed?

Group I: Single Oral Dose of 13C2-Glycolate Experimental Treatment 2 Interventions

Subjects will consume a controlled diet for 5 days total. On Days 3 and 4, subjects will collect 24 hour urines. On Day 5, they will come to the Clinical Research Unit (CRU) in the fasted state for a visit lasting from 7:00 am to 2:30 pm. At 8:30 am, subjects will ingest the carbon-13 glycolate, dissolved in to 50 ml (about 1/4 cup) of water. From 7:30 am to 2:30 pm, urine collections will occur hourly. At 8:30 am, intravenous (IV) blood samples will be taken every fifteen minutes until 9:30 am, every half hour from 9:30 am to 10:30 am, and then finally hourly from 10:30 am to 2:30 pm . Subjects will receive a meal at 2:30 pm, thus concluding the CRU visit. At home, subjects will collect timed urine until the next morning to be returned to the CRU.

Group II: Single Intravenous Dose of 13C2-Glycolate Experimental Treatment 2 Interventions

Subjects will consume a controlled diet for 5 days total. On Days 3 and 4, subjects will collect 24 hour urines. On Day 5, they will come to the Clinical Research Unit (CRU) in the fasted state for a visit lasting from 7:00 am to 2:30 pm. An intravenous (IV) catheter will be placed in a vein on the back of the hand at 8:30 am for a single dose of carbon-13 glycolate to be administered. From 7:30 am to 2:30 pm, urine collections will occur hourly. At 8:30 am, IV blood samples will be taken every fifteen minutes until 9:30 am, every half hour from 9:30 am to 10:30 am, and then finally hourly from 10:30 am to 2:30 pm . Subjects will receive a meal at 2:30 pm, thus concluding the CRU visit. At home, subjects will collect timed urine until the next morning to be returned to the CRU.

Group III: Constant Infusion of 13C2-Glycolate Experimental Treatment 2 Interventions

Subjects will consume a controlled diet for 5 days total. On Days 3 and 4, subjects will collect 24 hour urines. On Day 5, they will come to the Clinical Research Unit (CRU) in the fasted state for a visit lasting from 7:00 am to 5:30 pm. An intravenous (IV) catheter will be placed in a vein on the back of the hand at 7:30 am for the carbon 13 glycolate infusion which will occur at a constant rate for 10 hours, following a priming dose. From 7:30 am to 5:30 pm, urine collections will occur hourly, and from 8:30 am to 5:30 pm, IV blood collections will occur every half hour. Subjects will receive a meal at 5:30 pm, thus concluding the CRU visit. At home, subjects will collect timed urine until the next morning to be returned to the CRU.

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

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

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

A new ion chromatography coupled with mass spectrometry (IC-MS) method allows for the rapid quantification of glycolate and 2-phosphoglycolate in tissue samples, with analysis completed in under an hour.

Glycolate and 2-phosphoglycolate were found in low concentrations across various tissues, with glycolate levels ranging from 12-48 nmol/g and PG from 4-17 nmol/g, suggesting these compounds may have previously unrecognized metabolic roles in the body.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glycolate and 2-phosphoglycolate content of tissues measured by ion chromatography coupled to mass spectrometry. Knight, J., Hinsdale, M., Holmes, R.[2021]

Hyperpolarized 13C-labeled metabolic substrates can be used to monitor glycolysis and the pentose phosphate pathway in real time, providing insights into glucose metabolism in both healthy and diseased tissues.

This technique successfully visualizes elevated glycolysis in tumors, known as the Warburg effect, using specific 13C-labeled glucose derivatives, which could enhance our understanding of metabolic changes in cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Probing carbohydrate metabolism using hyperpolarized 13 C-labeled molecules. Singh, J., Suh, EH., Sharma, G., et al.[2023]

A new gas-liquid chromatographic/mass spectrometric method allows for the simultaneous measurement of plasma acetate content and tracer enrichment using only 200-500 microliters of plasma, demonstrating high precision (± 5%) in physiological acetate ranges.

This method was successfully applied to measure acetate turnover in a young adult, showcasing its potential for in vivo studies involving (2-13C)acetate as an isotopic tracer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capillary gas-liquid chromatographic/mass spectrometric measurement of plasma acetate content and (2-13C) acetate enrichment. Rocchiccioli, F., Lepetit, N., Bougnères, PF.[2006]

A new computer program was developed to accurately calculate and correct the mass isotopomer distribution of metabolites, which is crucial for understanding metabolic processes involving 13C-labeled substrates.

The program showed differences in corrected mass isotopomer distributions compared to classical techniques, which could impact the calculation of glucose production in metabolic studies, highlighting the importance of accurate isotopic analysis in metabolic research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Correction of 13C mass isotopomer distributions for natural stable isotope abundance. Fernandez, CA., Des Rosiers, C., Previs, SF., et al.[2013]

The study demonstrated that using 1-[(13)C]glucose with advanced measurement techniques can effectively replace the traditional 6,6-[(2)H(2)]glucose method for assessing glucose metabolism in various populations, including lean and obese individuals, those with impaired glucose tolerance, and diabetes.

This new method allows for a significant reduction in the amount of isotope needed (approximately 15-fold less), making it not only more cost-effective but also improving the accuracy of glucose metabolism measurements by achieving near-physiological conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

13C- and 2H-labelled glucose compared for minimal model estimates of glucose metabolism in man. Bluck, LJ., Clapperton, AT., Coward, WA.[2015]

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Conclusion: The No Observed Adverse Effect Concentration (NOAEC) for the nasal and pulmonary toxicity of glycolic acid was determined to be over 50 mg/m3 at the ...

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Glycolic acid-13C2 is an inhibitor of tyrosinase, suppressing melanin formation and lead to a lightening of skin colour.

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