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Study of Arginine and Nitric Oxide in Patients With Diabetes

Primary Purpose

Ketosis Prone Diabetes

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Citrulline
Alanine
Sponsored by
Baylor College of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ketosis Prone Diabetes

Eligibility Criteria

20 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Baylor St Lukes Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Citrulline

alanine

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Change in Arginine production
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
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
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
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.

Full Information

First Posted
May 31, 2018
Last Updated
July 27, 2022
Sponsor
Baylor College of Medicine
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1. Study Identification

Unique Protocol Identification Number
NCT03566524
Brief Title
Study of Arginine and Nitric Oxide in Patients With Diabetes
Official Title
Arginine and Nitric Oxide Synthesis in the Pathogenesis of Ketosis-prone Diabetes
Study Type
Interventional

2. Study Status

Record Verification Date
July 2022
Overall Recruitment Status
Completed
Study Start Date
July 1, 2018 (Actual)
Primary Completion Date
June 30, 2022 (Actual)
Study Completion Date
June 30, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Baylor College of Medicine

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ketosis Prone Diabetes

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderOutcomes Assessor
Allocation
Randomized
Enrollment
10 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Citrulline
Arm Type
Experimental
Arm Description
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.
Arm Title
alanine
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Dietary Supplement
Intervention Name(s)
Citrulline
Intervention Description
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.
Intervention Type
Dietary Supplement
Intervention Name(s)
Alanine
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change in Arginine production
Description
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.
Time Frame
Three weeks
Secondary Outcome Measure Information:
Title
Change in Nitric Oxide Synthesis
Description
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.
Time Frame
Three weeks
Title
Change in Arterial function
Description
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.
Time Frame
Three weeks
Title
Change in Insulin secretion
Description
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.
Time Frame
Three weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Baylor St Lukes Medical Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Study of Arginine and Nitric Oxide in Patients With Diabetes

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