Effect of L-Citrulline Supplementation on Arginase Activity and Vascular Function in Diabetes

Effect of L-Citrulline Supplementation on Arginase Activity and Vascular Function in Type II Diabetes Mellitus

Arginase has recently been implicated in an array of vascular conditions including atherosclerosis , hypertension and vascular complication of diabetes. In this study we will determine of L-citrulline; a natural amino acid that is known to have inhibitory effects on arginase activity, on vascular function in type 2 diabetic patients.

Study Overview

• Status: Unknown
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Dietary supplement: L-citrulline

Detailed Description

Vascular dysfunction is a major cause of morbidity and mortality in diabetic patients. The pathological process is characterized by impaired endothelial cell production of the vasodilator and antiplatelet adhesion factor nitric oxide (NO) and/or decreased NO bioavailability. NO is a major regulator of vascular tone and integrity. In endothelial cells, NO is produced by activity of endothelial NO synthase (eNOS) on its substrate L-arginine. Reduced availability of L-arginine to eNOS has been implicated in vascular dysfunction in diabetes and a variety of other disease conditions. Arginase, which metabolizes L-arginine to urea and ornithine, competes directly with NOS for L-arginine. Hence increases in arginase activity can decrease tissue and cellular arginine levels, reducing its availability to eNOS and decreasing No production. During diabetes, elevated levels of arginase can compete with NOS for available arginine thus reducing vascular NO. We have recently shown that arginase activity is elevated in diabetes. In this proposal we implement a method of flow mediate dilation (FMD) to assess vascular function in diabetic patients. We will study the relation of our vascular function findings with arginase activity levels. We propose that arginase activity measurements could be novel marker of vascular dysfunction in diabetes. The effect of the natural amino acid supplements (L-citrulline) on levels of arginase activity in diabetic patients and vascular function will also be studied.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Alia Shatanawi, PhD, DDS; Phone Number: 23458 +96265355000; Email: a.shatanawi@ju.edu.jo
• Study Contact Backup: Name: Munir N Gharaibeh, PhD, MD; Phone Number: 23456 96265355000; Email: mgharaib@ju.edu.jo

Study Locations

• Jordan
  • Amman, Jordan, 11942
    • Recruiting
    • The university of Jordan
    • Contact: Alia Shatanawi, PhD, DDS; Phone Number: 23458 +96265355000; Email: a.shatanawi@ju.edu.jo
    • Contact: Munir N Gharaibeh, PhD, MD; Phone Number: 23456 +96265355000; Email: mgharaib@ju.edu.jo
    • Sub-Investigator: Munther S Momani, MD
    • Principal Investigator: Alia Shatanawi, PhD, DDS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Type 2 diabetes Diabetic state: HbA1c>6

Exclusion Criteria:

-

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Type 2 diabetic patients; L-citrulline at a dose of 2000 mg per day for a period of 1 month will be administered to type 2 diabetic patients with HbA1c>6	Dietary supplement: L-citrulline; Amino acid supplement
Experimental: Healthy volunteers; L-citrulline at a dose of 2000 mg per day for a period of 1 month will be administered to non-diabetic healthy volunteers	Dietary supplement: L-citrulline; Amino acid supplement

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
arginase activity	Levels of arginase activity enzyme will be measured in plasma in subjects before and after l-citrulline supplementation	1 month
Vascular function	forearm vascular function will be assessed by flow mediated dilation of brachial blood vessels before and after L-citrulline supplementation	1 month

Collaborators and Investigators

• Sponsor: University of Jordan

Publications and helpful links

General Publications

• Shatanawi A, Momani, MS. Plasma arginase activity is elevated in type 2 diabetic patients. Biomedical Research-India 28(9): 4102-4106, 2017

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2017
• Primary Completion (Anticipated): December 31, 2018
• Study Completion (Anticipated): December 31, 2018

Study Registration Dates

• First Submitted: November 26, 2017
• First Submitted That Met QC Criteria: November 26, 2017
• First Posted (Actual): November 30, 2017

Study Record Updates

• Last Update Posted (Actual): November 30, 2017
• Last Update Submitted That Met QC Criteria: November 26, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: Vascular dysfunction, L-citrulline, arginase
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: Pharmacology-Medicine-UJ

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No