Study of Arginine and Nitric Oxide in Patients With Diabetes

Sponsor

Baylor College of Medicine (Other)

Overall Status

Completed

CT.gov ID

NCT03566524

Collaborator

(none)

Enrollment

Location

Arms

Actual Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will test the effect of citrulline versus placebo supplementation in ketosis-prone diabetes (KPD) patients on arginine and nitric oxide production and on glucose- and arginine-stimulated insulin secretion and arterial flow-mediated dilation.

Condition or Disease	Intervention/Treatment	Phase
Ketosis Prone Diabetes	Dietary Supplement: Citrulline Dietary Supplement: Alanine	N/A

Detailed Description

Both arginine and its derivative nitric oxide (NO) have been implicated in the regulation of glucose homeostasis. Arginine is a β cell secretagogue, potentiating glucose stimulated insulin secretion. Further, it has been shown that glucose can stimulate NO production in primary β cells, and NO then enhances insulin secretion.

On the other hand, because the only known fate of citrulline is its conversion to arginine, citrulline supplementation could be a more efficient and safe way to increase intracellular arginine. Compared to enteral arginine, citrulline administration to healthy humans elicited a greater increase in plasma arginine and NO products, suggesting a greater increase in cellular arginine availability for NO synthesis. Therefore dietary citrulline supplementation will result in greater arginine availability and NO synthesis than arginine supplementation per se in KPD patients. In addition, because the consequences of diminished NO production in usual type 2 diabetes includes vascular dysfunction, an overall increase in NO production in response to citrulline supplementation will result in an improvement in vascular function assessed by arterial flow-mediated dilation

Study Design

Study Type:

Interventional

Actual Enrollment :

10 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Arginine and Nitric Oxide Synthesis in the Pathogenesis of Ketosis-prone Diabetes

Actual Study Start Date :

Jul 1, 2018

Actual Primary Completion Date :

Jun 30, 2022

Actual Study Completion Date :

Jun 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Citrulline In this arm, 10 ketosis prone diabetes patients will be randomly assigned to receive 34.2 mmol/d of dietary citrulline for 20 days. Citrulline will be in the form of 2.85 mmol capsules and patients will be instructed to consume 4 capsules with each of their 3 main meals. The citrulline will be provided in a double-blind fashion by a designated unblinded investigator who will not come in direct contact with the subjects.	Dietary Supplement: Citrulline Ketosis prone diabetes patients (n=10) will be randomly assigned to receive either dietary supplement of citrulline or alanine as placebo. They will then cross over to the other supplement.
Placebo Comparator: alanine In this arm, 10 ketosis prone diabetes patients will be randomly assigned to receive 34.2 mmol/d of dietary alanine for 20 days. Alanine will be in the form of 2.85 mmol capsules and patients will be instructed to consume 4 capsules with each of their 3 main meals. The alanine will be provided in a double-blind fashion by a designated unblinded investigator who will not come in direct contact with the subjects.	Dietary Supplement: Alanine Ketosis prone diabetes patients (n=10) will be randomly assigned to receive either dietary supplement of citrulline or alanine as placebo. They will then cross over to the other supplement.

Arm

Intervention/Treatment

Experimental: Citrulline

In this arm, 10 ketosis prone diabetes patients will be randomly assigned to receive 34.2 mmol/d of dietary citrulline for 20 days. Citrulline will be in the form of 2.85 mmol capsules and patients will be instructed to consume 4 capsules with each of their 3 main meals. The citrulline will be provided in a double-blind fashion by a designated unblinded investigator who will not come in direct contact with the subjects.

Dietary Supplement: Citrulline

Ketosis prone diabetes patients (n=10) will be randomly assigned to receive either dietary supplement of citrulline or alanine as placebo. They will then cross over to the other supplement.

Placebo Comparator: alanine

In this arm, 10 ketosis prone diabetes patients will be randomly assigned to receive 34.2 mmol/d of dietary alanine for 20 days. Alanine will be in the form of 2.85 mmol capsules and patients will be instructed to consume 4 capsules with each of their 3 main meals. The alanine will be provided in a double-blind fashion by a designated unblinded investigator who will not come in direct contact with the subjects.

Dietary Supplement: Alanine

Ketosis prone diabetes patients (n=10) will be randomly assigned to receive either dietary supplement of citrulline or alanine as placebo. They will then cross over to the other supplement.

Outcome Measures

Primary Outcome Measures

Change in Arginine production [Three weeks]
The change in the amount of arginine produced from baseline in response to supplements of citrulline versus alanine (placebo) will be assessed by stable isotope tracers after 3 weeks of supplementation.

Secondary Outcome Measures

Change in Nitric Oxide Synthesis [Three weeks]
The change in the amount of nitric oxide produced produced from baseline in response to supplements of citrulline versus alanine (placebo) will be assessed by stable isotope tracers after 3 weeks of supplementation.
Change in Arterial function [Three weeks]
The change in in arterial function (assessed by endopat) from baseline in response to supplements of citrulline versus alanine placebo will be assessed after 3 weeks of supplementation.
Change in Insulin secretion [Three weeks]
The change in glucose stimulated insulin secretion from baseline in response to supplements of citrulline versus alanine placebo will be assessed after 3 weeks of supplementation.

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

New onset (defined as receiving a diagnosis within the past 1 year) diagnosis of unprovoked" A-β+ ketosis-prone diabetes
Aged 20-65 years
In good health except for diabetes without clinical evidence of micro- or macrovascular complications by history, physical exam and blood chemistries

Exclusion Criteria:

Chronic or acute illness
History of myocardial infarction or coronary artery disease or stroke,
Renal insufficiency (eGFR <90mL/min/1.73m2; <30 mg albumin / g creatinine in urine)
Abnormal liver, thyroid, gonadal or adrenal functions
On medications other than metformin,
On any hormonal replacement therapy
Pregnancy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Baylor St Lukes Medical Center	Houston	Texas	United States	77030

Sponsors and Collaborators

Baylor College of Medicine

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Farook Jahoor, Professor, Baylor College of Medicine

ClinicalTrials.gov Identifier:

NCT03566524

Other Study ID Numbers:

DK101411

First Posted:

Jun 25, 2018

Last Update Posted:

Jul 29, 2022

Last Verified:

Jul 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Diabetes Mellitus

Ketosis

Study Results

No Results Posted as of Jul 29, 2022