Type 2 DiabetesNCT05477134
Arginine Metabolism in Youth With Type 2 Diabetes
A study testing Stable isotope infusion, oral glucose ingestion, intravenous arginine bolus in people with Type 2 Diabetes, run by Baylor College of Medicine at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 12 to 20 yearsHealthy volunteers can take part
- Conditions the study is for
- Type 2 Diabetes
- What is being tested?
- Stable isotope infusion, oral glucose ingestion, intravenous arginine bolus
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Feb 2023to 18 Jun 2026
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 20 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- Youth with type 2 diabetes and healthy controls who meet other inclusion criteria outlined below.
- Age and pubertal stage criteria (12- to 20-year-old girls who are postmenarchal, and 14- to 20-year-old boys who are at Tanner stage 5 genitalia),
- Additional criteria for youth with diabetes: i. diagnosis of T2D, and ii. diabetes duration between 3 months and 10 years.
Who cannot join
- Previous history of diabetic ketoacidosis (DKA)
- Poorly controlled diabetes defined as HbA1c >7.5%,
- Abnormal liver, thyroid, gonadal or adrenal functions,
- Renal insufficiency defined by eGFR (estimated glomerular filtration rate) <90 mL/min/1.73 m2,
- Any glucose lowering medications except metformin, insulin and liraglutide
- Any medication use that will likely to interfere amino acid metabolism, (8) Any hormonal replacement therapy, and (9) Pregnancy.
Trial locations and contacts
1 site in 1 country.
United States1 site
Texas Children's Hospital / Baylor College of Medicine
Houston, Texas, 77030
About this study
Official title: Arginine Metabolism in Pediatric Type 2 Diabetes
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.
Read the detailed description
In parallel with the youth obesity epidemic, type 2 diabetes (T2D) in youth is becoming a significant public health concern. The incidence of pediatric T2D increased by 50% during the past decade, and recent data show that T2D accounts for one in four newly-diagnosed diabetes cases in children. Youth with T2D have an aggressive disease course and a rapid decline in β-cell function, and many also have multiple cardiovascular disease risk factors at an early age. The disease is characterized by insulin resistance and impaired insulin secretion, but the molecular underpinnings of T2D are not yet fully elucidated. This study aims to uncover the role of arginine metabolism in the pathogenesis of youth with T2D and the effect of exogenous arginine administration on β-cell function in them.
Arginine is a known stimulant of insulin secretion in pancreatic β-cells. Nitric oxide (NO) is synthesized from arginine by NO synthase, and arginine stimulates insulin secretion in both NO-mediated and NO-independent mechanisms by stimulating guanylate cyclase, membrane depolarization, and metabolic by-products. The effects of arginine in pancreatic β-cells are dependent on the cells' available arginine concentration. Kinetic techniques using isotope tracer infusions and targeted metabolomics provide a unique opportunity to determine "intracellular" arginine availability and its relative contribution of various pathways to this pool. Such studies in adults with T2D have shown that arginine and NO play roles in the pathogenesis of T2D by affecting insulin secretion and insulin sensitivity. In the preliminary data on children with T2D, the investigators found that children with T2D had lower fasting arginine, citrulline (arginine precursor), and glutamine (citrulline precursor) levels. In this proposal, the investigators will seek kinetic validation of these hypothesis-generating observations to investigate the role of arginine metabolism in youth with T2D. Our central hypothesis is that youth with T2D have inadequate arginine availability (Aim 1), leading to suboptimal β-cell function, which can be restored by exogenous arginine administration (Aim 2). If our hypotheses are proven, arginine supplementation will play a clinically vital role in improving diabetes outcomes in this population as a safe, low-cost, and readily available nutrient.
- Conditions
- Type 2 Diabetes
- Being tested
- Stable isotope infusion, oral glucose ingestion, intravenous arginine bolus
- Keywords
- Children, Pediatric type 2 diabetes, Pediatric diabetes, Arginine, Youth
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Stable isotope infusion, oral glucose ingestion, intravenous arginine bolusOther
On separate study days, each participant will have a stable isotope infusion, ingest oral glucose, and be given an intravenous arginine bolus.
| Study group | Role | What they receive |
|---|---|---|
| The study cohort consisting of youth with type 2 diabetes and healthy controls | Experimental | 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. Receives: Other: Stable isotope infusion, oral glucose ingestion, intravenous arginine bolus |
What is being measured
The primary outcome is the main question the study is designed to answer.
The difference in arginine availability
Arginine availability will be assessed and compared between youth with type 2 diabetes and healthy controls.
Measured: 1 day
Secondary outcomes (2)
The difference in insulin secretion and the effect of intravenous arginine bolus on insulin secretion
Insulin secretion will be assessed and compared between youth with type 2 diabetes and healthy controls using oral glucose tolerance tests and modified oral glucose tolerance tests including intravenous arginine administration. The effect of arginine bolus on insulin secretion will be compared between the groups.
Measured: 1 day
The difference in insulin sensitivity and the effect of intravenous arginine bolus on insulin sensitivity
Insulin sensitivity will be assessed and compared between youth with type 2 diabetes and healthy controls using oral glucose tolerance tests and modified oral glucose tolerance tests including intravenous arginine administration. The effect of arginine bolus on insulin sensitivity will be compared between the groups.
Measured: 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2022
- Study start6 Feb 2023
- Primary completion18 Jun 2026
- Study completion18 Jun 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 2 DiabetesStudies of the same condition, open and under way.
- More trials run by Baylor College of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baylor College of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mustafa Tosur, Baylor College of Medicine
- Investigators
- Mustafa Tosur, MD, Principal investigator, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05477134
- Sponsor's protocol ID
- H-51936
- Status last verified
- Aug 2026
- First submitted
- 25 Jul 2022
- Last updated
- 13 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Arginine Metabolism in Pediatric Type 2 Diabetes
- ClinicalTrials.gov ID
- NCT05477134
- Acronym / sponsor ID
- H-51936
- Conditions
- Type 2 Diabetes
- Keywords
- Children, Pediatric type 2 diabetes, Pediatric diabetes, Arginine, Youth
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Baylor College of MedicineUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 6 Feb 2023 (actual)
- Primary completion
- 18 Jun 2026 (actual)
- Study completion
- 18 Jun 2026 (actual)
- First posted
- 28 Jul 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
In parallel with the youth obesity epidemic, type 2 diabetes (T2D) in youth is becoming a significant public health concern. The incidence of pediatric T2D increased by 50% during the past decade, and recent data show that T2D accounts for one in four newly-diagnosed diabetes cases in children. Youth with T2D have an aggressive disease course and a rapid decline in β-cell function, and many also have multiple cardiovascular disease risk factors at an early age. The disease is characterized by insulin resistance and impaired insulin secretion, but the molecular underpinnings of T2D are not yet fully elucidated. This study aims to uncover the role of arginine metabolism in the pathogenesis of youth with T2D and the effect of exogenous arginine administration on β-cell function in them.
Arginine is a known stimulant of insulin secretion in pancreatic β-cells. Nitric oxide (NO) is synthesized from arginine by NO synthase, and arginine stimulates insulin secretion in both NO-mediated and NO-independent mechanisms by stimulating guanylate cyclase, membrane depolarization, and metabolic by-products. The effects of arginine in pancreatic β-cells are dependent on the cells' available arginine concentration. Kinetic techniques using isotope tracer infusions and targeted metabolomics provide a unique opportunity to determine "intracellular" arginine availability and its relative contribution of various pathways to this pool. Such studies in adults with T2D have shown that arginine and NO play roles in the pathogenesis of T2D by affecting insulin secretion and insulin sensitivity. In the preliminary data on children with T2D, the investigators found that children with T2D had lower fasting arginine, citrulline (arginine precursor), and glutamine (citrulline precursor) levels. In this proposal, the investigators will seek kinetic validation of these hypothesis-generating observations to investigate the role of arginine metabolism in youth with T2D. Our central hypothesis is that youth with T2D have inadequate arginine availability (Aim 1), leading to suboptimal β-cell function, which can be restored by exogenous arginine administration (Aim 2). If our hypotheses are proven, arginine supplementation will play a clinically vital role in improving diabetes outcomes in this population as a safe, low-cost, and readily available nutrient.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| The study cohort consisting of youth with type 2 diabetes and healthy controls | Experimental | Other: Stable isotope infusion, oral glucose ingestion, intravenous arginine bolusIn 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. |
Who may qualify
- Ages
- 12 to 20 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- Youth with type 2 diabetes and healthy controls who meet other inclusion criteria outlined below.
- Age and pubertal stage criteria (12- to 20-year-old girls who are postmenarchal, and 14- to 20-year-old boys who are at Tanner stage 5 genitalia),
- Additional criteria for youth with diabetes: i. diagnosis of T2D, and ii. diabetes duration between 3 months and 10 years.
Key exclusion criteria (6 listed)
- Previous history of diabetic ketoacidosis (DKA)
- Poorly controlled diabetes defined as HbA1c >7.5%,
- Abnormal liver, thyroid, gonadal or adrenal functions,
- Renal insufficiency defined by eGFR (estimated glomerular filtration rate) <90 mL/min/1.73 m2,
- Any glucose lowering medications except metformin, insulin and liraglutide
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Stable isotope infusion, oral glucose ingestion, intravenous arginine bolusOn separate study days, each participant will have a stable isotope infusion, ingest oral glucose, and be given an intravenous arginine bolus. | Other | The study cohort consisting of youth with type 2 diabetes and healthy controls |
Primary outcome
The difference in arginine availability
Time frame: 1 day
Arginine availability will be assessed and compared between youth with type 2 diabetes and healthy controls.
2 secondary outcomes
The difference in insulin secretion and the effect of intravenous arginine bolus on insulin secretion
Time frame: 1 day
The difference in insulin sensitivity and the effect of intravenous arginine bolus on insulin sensitivity
Time frame: 1 day
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mustafa Tosur, MD principal investigator
Baylor College of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Stable isotope infusion, oral glucose ingestion, intravenous arginine bolus in people with Type 2 Diabetes, run by Baylor College of Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The difference in arginine availability (time frame: 1 day). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Aug 2026.