A Phase 1/2 interventional study of Arginine hydrochloride and Sodium Chloride 0.9% in Diabetes (DM), Diabetic Ketoacidosis and Ketosis Prone Diabetes, sponsored by David K Carroll. Recruiting at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-02-12.
Sponsored by David K Carroll · Phase 1/2, Interventional, and Treatment
Among 31 studies in Diabetic Ketoacidosis with a site in United States — 5 open to participants now, 5 under way, none of them phase 3. Diabetic Ketoacidosis · United States.
Among the 31 studies in Diabetic Ketoacidosis with a site in United States, this one is the 11th largest by planned enrollment of the 23 interventional ones that give a count, is one of 3 that started in 2025, is the only one in phase 1/2, and was the 30th registered.
76 studies on the registry are indexed under Diabetic Ketoacidosis; 17 are open to participants now.
Browse Diabetic Ketoacidosis studies →5 of the 31 studies in Diabetic Ketoacidosis with a site in United States are open now. Recruiting first, the newest first:
Boston Medical Center · Sites in United States
Emory University · Sites in United States
Sanford Health · Sites in United States
HealthPartners Institute · Sites in United States
A study can be open while its sites in United States have not opened yet or have stopped. Only those recruiting at a site in United States →
Of the 11 Diabetic Ketoacidosis studies recruiting now, 5 (45%) set no upper age limit and 6 (55%) stop at 75 or younger; 3 take children under 18; 3 take healthy volunteers.
This study: 18 Years and older · all sexes · no healthy volunteers.
The full table on the hub →This tab as a report to print or save as PDF → With an account.
31 studies; the count open now beside each. This study's row is marked.
A study in two phases is counted once above. Listed by phase, each with its combined phases: Phase 1 1 · Phase 2 3 · Phase 3 1 · Phase 4 5
First in 2004; this study’s year is marked. 3 started in 2025.
This study's planned enrollment of 60 is close to the median of 66 across 44 interventional studies indexed under Diabetic Ketoacidosis.
Median enrollment 57 across the 23 interventional studies, 53 across the 8 observational. Of the 24 that completed or were terminated, 12 (50%) have results posted.
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1 of 31 have an industry lead sponsor. The 10 most frequent:
This is the only study on the registry with David K Carroll as lead sponsor.
David K Carroll has 1 study filed under Diabetic Ketoacidosis — fewer than ten, so there is no comparison to draw.
2 of the studies in Diabetic Ketoacidosis with a site in United States that are under way reach primary completion within a year, 0 of them phase 3. Phase 3 first, then by date:
| Study | Primary completion |
|---|---|
| NCT06699810Emory UniversityModeling Ketosis-Prone Diabetes Remission Via Diverse Mechanisms of Glucotoxicity | 2027-01 |
| NCT07167693David K CarrollPhase 1 Trial of Arginine Hydrochloride for the Management of Diabetic Ketoacidosis in Type 2 Diabetes | 2027-10-31 |
Among the 31 studies in Diabetic Ketoacidosis with a site in United States, from their registry updates:
Nothing recorded among them since 2026-09-25.
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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.
Background and Rationale. A substantial subset of adults with type 2 diabetes develop DKA ("ketone-prone" type 2 diabetes). Many of these patients lack diabetes autoantibodies (A-) and retain recoverable β-cell function (β+). The pathophysiology appears to involve reversible β-cell dysfunction from prolonged hyperglycemia. Arginine, a cationic amino acid and physiologic insulin secretagogue, depolarizes β-cells and enhances glucose-dependent insulin release within minutes. Prior human studies show prompt rises in insulin and C-peptide after arginine in individuals with preserved β-cell reserve. Arginine may also improve nitric-oxide bioavailability and mitigate mitochondrial dysfunction-processes implicated in hyperglycemic crises. We therefore hypothesize that early intravenous arginine, added to usual DKA care, will acutely increase endogenous insulin secretion and speed clearance of ketosis without added safety concerns.
Design and Setting. Prospective, phase 1/2, randomized, double-blind, placebo-controlled, parallel-group trial at four emergency departments in the Detroit metropolitan area. Target enrollment is 60 participants (1:1 allocation).
Participants. Adults (>17 years) with hyperglycemia (generally ≥250 mg/dL) and significant ketonemia/ketosis consistent with DKA and a clinical phenotype of ketone-prone type 2 diabetes. Key exclusions include known type 1 diabetes or positive GAD65 antibodies, chronic dialysis, cirrhosis, pregnancy, allergy to arginine, or features of moderate/greater alcohol intoxication. Screening may use point-of-care capillary β-hydroxybutyrate (BHB) or breath acetone to expedite identification; confirmatory laboratory thresholds will be used per protocol.
Intervention. As early as logistics allow after recognition of DKA, participants will receive a blinded 30-minute intravenous infusion of either arginine hydrochloride 30 g in 300 mL (R-Gene® 10) or matching placebo (normal saline 500 mL). Treating teams will manage DKA per standard institutional protocols; the study does not restrict clinical care (fluids, insulin, electrolytes).
Outcomes.
Primary endpoint: Endogenous insulin secretion quantified by the C-peptide/glucose ratio at 10, 30 (end of infusion), and 90 minutes after infusion start.
Key secondary endpoints: (a) Rate of BHB decline (ketone clearance), and (b) total insulin administered in the first 24 hours.
Mechanistic/biomarker endpoints: Plasma amino acids-especially arginine, citrulline, and ornithine-to compute the Global Arginine Bioavailability Ratio (arginine/[ornithine+citrulline]) at baseline and 90 minutes; insulin, proinsulin, and diabetes autoantibodies. Exploratory endpoint: Platelet mitochondrial complex IV and V activities as markers of oxidative phosphorylation.
Safety Monitoring. Participants will be observed closely during and after infusion with serial vital signs and symptom checks (e.g., flushing, nausea, headache). Pre-specified stop criteria allow immediate interruption of the infusion. Adverse events will be assessed to 90 days (telephone/medical record review) and reported per regulatory guidance. Because of the small size and favorable safety profile of intravenous arginine, the study qualifies as early-phase with streamlined oversight; an independent Data and Safety Monitoring Board has nonetheless been chartered.
Sample Size and Analysis. Based on prior insulinotropic responses to arginine, we powered the study to detect a moderate-to-large effect (standardized mean difference \~0.8) in the primary endpoint with 80% power and α=0.05, yielding \~26 per group. Allowing for attrition, we plan to enroll 60 participants. The C-peptide/glucose ratio will be assessed for normality and compared between groups with appropriate parametric or transformed analyses; ketone clearance and insulin dose will be analyzed similarly. Prespecified sensitivity analyses will account for baseline severity and timing of insulin initiation.
Operational Notes. To facilitate early enrollment, research staff will screen patients with suspected DKA using point-of-care BHB or breath acetone while confirmatory labs are pending. Blood draws for study assays occur at baseline (pre-infusion), 10, 30, and 90 minutes, with additional clinically obtained labs used for outcomes (e.g., BHB over the first 24 hours). Platelet-rich plasma will be stored for exploratory mitochondrial testing using validated methods.
Impact. If early arginine infusion safely augments endogenous insulin and accelerates ketone clearance, this pragmatic, low-cost, readily available therapy could reduce reliance on prolonged insulin infusions, shorten ICU/ED resource use, and improve patient experience during DKA. Findings will inform the design of a larger phase 2/3 trial focused on clinical effectiveness and health-system outcomes in ketone-prone type 2 diabetes.
76 studies on the registry are indexed under Diabetic Ketoacidosis; 17 are open to participants now.
This study's planned enrollment of 60 is close to the median of 66 across 44 interventional studies indexed under Diabetic Ketoacidosis.
Browse Diabetic Ketoacidosis studies →This is the only study on the registry with David K Carroll as lead sponsor.
Compared within Diabetic Ketoacidosis, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Diabetes Mellitus. The counts are of registry records indexed under each term, refreshed daily. How we classify →
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
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.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Drug: Arginine hydrochloride
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).
Drug: Sodium Chloride 0.9%
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.
Also known as: L-arginine hydrochloride, Arginine HCl, R-Gene 10, Arginine hydrochloride injection 10%
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.
Also known as: Normal saline
Change in endogenous insulin secretion (C-peptide/glucose ratio)
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.
Time frame: Baseline (pre-infusion) to 90 minutes after infusion start
Change in beta-hydroxybutyrate (BHB) concentration
Difference in serum BHB from baseline to 24 hours (baseline BHB minus 24-hour BHB). Positive values reflect ketone clearance.
Time frame: Baseline to 24 hours
Rate of BHB clearance
Slope of BHB concentration over time using all clinically obtained values in the first 24 hours.
Time frame: 0-24 hours
Total insulin administered in first 24 hours
Sum of all insulin doses (IV and/or subcutaneous) administered as part of routine care.
Time frame: 0-24 hours
Plasma arginine concentration (change from baseline)
HPLC-based quantification of plasma arginine at baseline and 90 minutes; change = 90-min minus baseline.
Time frame: Baseline to 90 minutes
Global Arginine Bioavailability Ratio (GABR)
GABR = \[arginine\]/(\[ornithine\]+\[citrulline\]); change from baseline to 90 minutes.
Time frame: Baseline to 90 minutes
Platelet mitochondrial complex IV activity (change from baseline)
Enzymatic activity of cytochrome c oxidase (complex IV) measured in isolated platelet-rich plasma; normalized to protein content or citrate synthase as per lab SOP; change = 90-min minus baseline.
Time frame: Baseline to 90 minutes
Platelet mitochondrial complex V (ATP synthase) activity (change from baseline)
Activity measured in isolated platelets; normalized per lab SOP; change = 90-min minus baseline.
Time frame: Baseline to 90 minutes
Plan to share: Yes — We will share de-identified individual participant data (IPD) underlying the primary and secondary outcomes, including: demographics (age, sex), baseline clinical values, all C-peptide and glucose measurements at 0/10/30/90 minutes, β-hydroxybutyrate values used to derive ketone-clearance metrics, total insulin administered in the first 24 hours, adverse events, and (when available) amino-acid measures and platelet mitochondrial assays. A data dictionary will accompany the dataset. All IPD will be de-identified consistent with HIPAA Safe Harbor (direct identifiers removed; dates converted to study day/time; site identifiers suppressed).
Supporting information: Study protocol, Statistical analysis plan, Analytic code
Time frame: Beginning after publication of the primary results manuscript (or within 24 months of last-patient last-visit, whichever occurs first) and available for at least 5 years thereafter.
Access criteria: Access is provided upon reasonable request to the Study Contact listed on this record. Requestors must submit a brief proposal with analysis aims and statistical plan and provide evidence of IRB/ethics review or exemption. A Data Use Agreement is required (no re-identification, no onward sharing, secure storage, and acknowledgment of the source in resulting works). Approved requests will receive the de-identified dataset and data dictionary via secure transfer. Aggregated results will also be made available on reasonable request.
No publications or documents are linked to this record.
Started Dec 2025 (actual). Primary completion is estimated for Oct 2027, 22 months after the start.
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