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Study of Arginine and Nitric Oxide in Patients With Diabetes

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ClinicalTrials.gov Identifier: NCT03566524
Recruitment Status : Recruiting
First Posted : June 25, 2018
Last Update Posted : July 21, 2021
Sponsor:
Information provided by (Responsible Party):
Farook Jahoor, Baylor College of Medicine

Brief Summary:
This study will test the effect of arginine versus citrulline versus placebo supplementation In three groups of 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: arginine Dietary Supplement: Citrulline Dietary Supplement: Alanine Not Applicable

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 39 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 : July 1, 2018
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : December 31, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arginine
In this experimental arm, 13 ketosis prone diabetes patients will be randomly assigned to receive 34.2 mmol/d of dietary arginine for 21 days. Arginine 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 arginine 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: arginine
Ketosis prone diabetes patients (n=13) will be randomly assigned to receive dietary supplements of arginine

Active Comparator: Citrulline
In this arm, 13 ketosis prone diabetes patients will be randomly assigned to receive 34.2 mmol/d of dietary citrulline for 21 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=13) will be randomly assigned to receive dietary supplements of citrulline

Placebo Comparator: alanine
In this arm, 13 ketosis prone diabetes patients will be randomly assigned to receive 34.2 mmol/d of dietary alanine for 21 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=13) will be randomly assigned to receive dietary supplements of alanine as placebo




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


Secondary Outcome Measures :
  1. Change in Nitric Oxide Synthesis [ Time Frame: Three weeks ]
    The change in the amount of nitric oxide produced produced from baseline in response to supplements of arginine versus citrulline versus alanine (placebo) will be assessed by stable isotope tracers after 3 weeks of supplementation.

  2. Change in Arterial function [ Time Frame: Three weeks ]
    The change in in arterial function (assessed by endopat) from baseline in response to supplements of arginine versus citrulline versus alanine placebo will be assessed after 3 weeks of supplementation..

  3. Change in Insulin secretion [ Time Frame: Three weeks ]
    The change in glucose stimulated insulin secretion from baseline in response to supplements of arginine versus citrulline versus alanine placebo will be assessed after 3 weeks of supplementation.



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Ages Eligible for Study:   20 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03566524


Contacts
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Contact: FAROOK JAHOOR, PhD 7137987084 fjahoor@bcm.edu
Contact: Ashok Balasubramanyam, MD 7137988654 ashokb@bcm.edu

Locations
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United States, Texas
Baylor St Lukes Medical Center Recruiting
Houston, Texas, United States, 77030
Contact: Mark J Biscome, PhD         
Sponsors and Collaborators
Baylor College of Medicine
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Responsible Party: Farook Jahoor, Professor, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT03566524    
Other Study ID Numbers: DK101411
First Posted: June 25, 2018    Key Record Dates
Last Update Posted: July 21, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Diabetes Mellitus
Ketosis
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Acidosis
Acid-Base Imbalance