NCT07167693 · David K Carroll
Phase 1 Trial of Arginine Hydrochloride for the Management of Diabetic Ketoacidosis in Type 2 Diabetes
What this study is about
Diabetic ketoacidosis (DKA) is increasingly recognized in adults with "ketone-prone" type 2 diabetes. In many of these patients, the pancreas can still make insulin but becomes temporarily "stunned" during severe, prolonged high blood sugar. Arginine is a naturally occurring amino acid that can trigger the pancreas to release its own insulin when glucose is high.
View original scientific description
Diabetic ketoacidosis (DKA) is increasingly recognized in adults with "ketone-prone" type 2 diabetes. In many of these patients, the pancreas can still make insulin but becomes temporarily "stunned" during severe, prolonged high blood sugar. Arginine is a naturally occurring amino acid that can trigger the pancreas to release its own insulin when glucose is high. It is FDA-approved for other uses and has been given intravenously for decades with a strong safety record. Whether a single arginine infusion given early during DKA can safely boost the body's insulin and speed recovery has not been tested. This randomized, double-blind, placebo-controlled, phase 1/2 trial will enroll 60 adults who present to one of four Detroit-area emergency departments with DKA consistent with ketone-prone type 2 diabetes (high glucose and significant ketones). Participants will receive standard DKA care ordered by their clinicians. In addition, under blinded conditions they will receive either arginine hydrochloride 30 grams (in 300 mL) or placebo (normal saline), infused intravenously over 30 minutes as early as feasible after DKA is recognized. The main question is whether arginine increases endogenous (self-made) insulin soon after infusion. We will measure C-peptide (a marker released in equal amounts with insulin) and glucose at 10, 30, and 90 minutes after the start of the infusion and calculate the C-peptide/glucose ratio. Secondary measures include the rate of ketone (β-hydroxybutyrate) clearance and the total insulin dose required in the first 24 hours. Additional blood tests will examine arginine and related amino acids, and a small sample of platelets will be used to explore mitochondrial function. Safety will be closely monitored during and after the infusion, and participants will be contacted at 90 days to assess for any delayed problems. Potential risks include temporary flushing, nausea, or headache; the infusion can be stopped at any time if needed. Potential benefits include faster resolution of ketosis and reduced insulin needs, but benefits cannot be guaranteed for individual participants.
Interventions
DRUG
Arginine hydrochloride
Single intravenous infusion of arginine hydrochloride 30 g in 300 mL 10% solution (R-Gene® 10), administered over 30 minutes via infusion pump. Given as early as feasible after recognition of DKA and in addition to standard DKA care (fluids, insulin, electrolytes) at the treating clinician's discretion. Investigational pharmacy prepares and dispenses blinded study drug; containers are covered to mask appearance and infusion parameters match placebo. Continuous safety monitoring with prespecified stop criteria. Study blood draws at 0 (pre-infusion), 10, 30, and 90 minutes for C-peptide/glucose and amino acids; clinical labs track β-hydroxybutyrate clearance and total insulin over 24 hours.
DRUG
Sodium Chloride 0.9%
Placebo comparator: 0.9% sodium chloride administered as a single 30-minute intravenous infusion using identical tubing, pump settings, and covered container as the active arm to preserve blinding. Initiated as early as feasible after recognition of DKA and provided in addition to standard DKA care at the treating clinician's discretion. Study assessments occur on the same schedule as the active arm (0, 10, 30, and 90 minutes) with continuous safety monitoring during and after infusion and follow-up through 90 days.
Primary outcome measures
Change in endogenous insulin secretion (C-peptide/glucose ratio)
Time frame: Baseline (pre-infusion) to 90 minutes after infusion start
Serum C-peptide (ng/mL) and plasma glucose (mg/dL) will be measured at 0 (pre-infusion), 10, 30, and 90 minutes from infusion start. The C-peptide/glucose ratio will be calculated at each time. Primary summary = change from baseline to 90 minutes (90-min ratio minus baseline ratio). Higher values indicate greater recruitable endogenous insulin secretion.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- Age \>17 years.
- Unscheduled presentation to a participating emergency department with hyperglycemia (serum glucose \>250 mg/dL) and significant ketonemia consistent with DKA, defined as laboratory serum/plasma β-hydroxybutyrate (BHB) \>20 mg/dL (≈≥1.9 mmol/L). Note: point-of-care capillary BHB ≥1.5 mmol/L and/or breath acetone ≥0.01% may be used for screening while confirmatory labs are pending; if confirmatory BHB ≤20 mg/dL, the participant is a screen failure.
- Clinical phenotype consistent with ketosis-prone type 2 diabetes (no known prior diagnosis of type 1 diabetes).
- Able to provide written informed consent and comply with study procedures in the ED.
Exclusion criteria
- Current renal replacement therapy for chronic kidney disease (hemodialysis or peritoneal dialysis).
- Known history of type 1 diabetes mellitus or known GAD65 autoantibody positivity.
- Diagnosed cirrhosis/advanced chronic liver disease.
- Pregnancy (known pregnancy or positive test at screening).
- Known allergy or hypersensitivity to arginine or its components.
- Features of at least moderate acute alcohol intoxication at screening, per treating team.
Where
- Detroit, Michigan
Collaborators
Wayne State University, Detroit Medical Center
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Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Feb 12, 2026 · Source of record for eligibility and locations