Phase 1 Trial of Arginine Hydrochloride for the Management of Diabetic Ketoacidosis in Type 2 Diabetes

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)

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.

Sponsors & Collaborators

• Wayne State University

  collaborator OTHER

• Detroit Medical Center

  collaborator OTHER

• David K Carroll

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-12-19

Primary Completion

2027-10-31

Completion

2027-12-31

FDA Drug

Yes

Countries

• United States

Study Locations