Recruiting
Phase 1
Phase 2

Arginine

Sponsor:

David K Carroll

Code:

NCT07167693

Conditions

Diabetes (DM)

Diabetic Ketoacidosis

Ketosis Prone Diabetes

Hyperglycaemia (Diabetic)

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Arginine hydrochloride

Sodium Chloride 0.9%

Study Details

Brief summary:

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.

Conditions

Diabetes (DM)

Diabetic Ketoacidosis

Ketosis Prone Diabetes

Hyperglycaemia (Diabetic)

Study ID

NCT07167693

Start date

Dec 19, 2025

Status verified date

Feb, 2026

Completion date

Dec 31, 2027

Anticipated

Primary completion date

Oct 31, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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.

Study Design

Enrollment

60 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

active comparator: Arginine Hydrochloride 30 g IV + Standard DKA Care

Single, blinded 30-minute intravenous infusion of arginine hydrochloride 30 g/300 mL (R-Gene® 10), initiated as early as feasible after recognition of DKA, in addition to standard DKA management (fluids, insulin, electrolytes) at the treating clinician's discretion. Infusion procedures are matched to placebo (covered containers; standardized pump settings) to maintain blinding. Study blood draws occur at 0 (pre-infusion), 10, 30, and 90 minutes for C-peptide/glucose and targeted amino acids; clinical labs are used to assess β-hydroxybutyrate clearance and total insulin administered in the first 24 h.

placebo comparator: Placebo (0.9% Saline) IV + Standard DKA Care

Single, blinded 30-minute intravenous infusion of matching placebo: 0.9% sodium chloride (normal saline) in a 500 mL container, administered at a standardized rate to mimic the active arm, plus standard DKA management directed by the treating team. Appearance and administration procedures match the arginine arm (covered containers; identical pumps/tubing) to preserve blinding. Study blood draws and assessments occur on the same schedule as the arginine arm (0, 10, 30, and 90 minutes).

Interventions

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.

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 measure

  • Change in endogenous insulin secretion (C-peptide/glucose ratio) [ Time Frame: Baseline (pre-infusion) to 90 minutes after infusion start ]

Central Contacts and Locations

Central contacts

David K Carroll, M.D.

16175830221hj7218@wayne.edu

Locations

Detroit Medical Center

Recruiting

Detroit, Michigan, United States, 48201

Contacts

David K Carroll, M.D.

6175830221hj7218@wayne.edu

More Information

Sponsor

David K Carroll

Last update posted

Feb 12, 2026

Last verified

Feb, 2026

Keywords

  • Arginine hydrochloride
  • Arginine
  • R-Gene 10
  • Insulin secretagogue
  • Endogenous insulin secretion
  • C-peptide
  • C-peptide to glucose ratio
  • Type 2 ketosis-prone diabetes (T2KPD)
  • Flatbush diabetes
  • Ketosis-prone diabetes (KPD)
  • Hyperglycemic crisis
  • Nitric oxide (NO)
  • Global arginine bioavailability ratio (GABR)
  • Mitochondrial function

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by David K Carroll on 2026-02-12.