Exercise Capacity and Quality of Life in Patients With PPH Receiving Short Term Oral L-Citrulline Malate

Exercise Capacity and Quality of Life in Patients With Idiopathic Pulmonary Hypertension and Eisenmenger Syndrome Receiving Short Term Oral L-Citrulline Malate

Due to vasodilatory properties of the NO, one of the therapeutic approaches for IPAH is oral use of nitric oxide precursors (10). Efficacy of L-arginine is well-documented in the current literature but there is paucity of data with regard to L-citrulline- malate. Hence, this study will evaluate therapeutic efficacy of L-citrulline- malate in two categories of patients with pulmonary hypertension (IPAH, and Eisenmeger syndrome). This randomized clinical trial utilizes 6-minute walk, pro BNP levels and the echocardiographic indexes an indicator of functional improvement of the patients.

Study Overview

• Status: Unknown
• Conditions: Idiopathic Pulmonary Arterial Hypertension; Eisenmenger Syndrome
• Intervention / Treatment: Drug: L-Citrulline Malate

Detailed Description

Pulmonary vascular tone is maintained by the action of vasoprotective compounds including nitric oxide (NO)(1).NO can be synthesized endogenously in the body via L-arginine and NOS-independent mechanism from the anion nitrite (NO2-)(2,3).Nitric oxide (NO) causes cyclic guanosine monophosphate-mediated vasodilatation of the pulmonary vasculature. Endogenous NO is also produced from the metabolism of citrulline; an amino acid generated by the urea cycle (4). NO is critical for normal development of the pulmonary vasculature and loss of this vasodilator factor and subsequent endothelial dysfunction is proposed as one of the possible explanations for development of pulmonary hypertension (1).

From a clinical standpoint, pulmonary hypertension is a common complication of chronic obstructive pulmonary disease (COPD).Its presence is associated with shorter survival and worse clinical outcome. In a setting of COPD, pulmonary hypertension tends to be of moderate severity and progresses slowly. Recent investigations have demonstrated endothelial dysfunction and changes in the expression of endothelial-derived mediators that regulate vascular tone and cell growth in the pulmonary arteries of patients with mild disease(5). Pulmonary vascular involvement from congenital heart disease like Eisenmeger syndrome is another important category of patients with PAH. In this congenital disease pulmonary vascular involvement follows a period in which pulmonary resistance is low and pulmonary blood flow is high (6, 7, 8). Finally, Idiopathic pulmonary hypertension (IPAH) is the third category of these patients. IPAH has unknown etiology and is characterized by progressive obliteration of small and medium size pulmonary arteries; elevation in pulmonary arterial pressure, and an increase in pulmonary vascular resistance. Presence of these pathologies eventually leads to right heart failure and death (9).

• Study Type: Interventional
• Enrollment (Anticipated): 25
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: babak sharif kashani, cardiologist; Phone Number: 0098-02188883114; Email: sharifk@nritld.ac.ir
• Study Contact Backup: Name: paritash tahmasebpour, MD; Phone Number: 0098-09125037861; Email: paritash_t@yahoo.com

Study Locations

• Iran, Islamic Republic of
  • Tehran, Iran, Islamic Republic of, 021
    • Recruiting
    • MasihDH
    • Contact: babak sharif kashani, cardiologist; Phone Number: 0098-02188883114; Email: sharifk@nritld.ac.ir
    • Contact: paritash tahmasebpour, MD; Phone Number: 0098-09125037861; Email: paritash_t@yahoo.com
    • Principal Investigator: babak sharif kashani, cardiologist

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years to 68 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• all patients less than 70 years old,
• patients with a six-minute walking distance of more than 100 meters (m),
• a mean pulmonary arterial pressure (PAP) ≥ 25 mmHg at rest as assessed by right heart catheterization(RHC) (11,12).

Exclusion Criteria:

• all patients more than 70 years old,
• patients with a six-minute walking distance of less than 100 meters (m), active pulmonary or extra pulmonary infection,
• serious coronaropathy and/ or ventricular dysfunction,
• significant renal illness and/or hepatitis,
• detected immunosuppressive illnesses,
• carrier of known neoplasias,
• pregnancy,
• lack of family support,
• psychosocial problems,
• drug or alcohol abuse, and
• noncompliance with established medical protocol.

Study Plan

How is the study designed?

Design Details

• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: L-Citrulline, Exercise Capacity; L-Citrulline malate, 1gr, oral, divided 3 times a day,for 2 weeks	Drug: L-Citrulline Malate; 3 gr per day, oral, for 2 weeks; Other Names: Stimol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the change in exercise capacity	The primary measure of efficacy was the change in exercise capacity, as measured by the total distance walked in six minutes, from baseline to week 2. (15)	2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
changes in mean pulmonary-artery pressure	changes in mean pulmonary-artery pressure from baseline to week 2.	2 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in the quality of life	change in the quality of life from baseline to week 2	2 weeks

Collaborators and Investigators

• Sponsor: Masih Daneshvari Hospital
• Investigators: Principal Investigator: babak sharif kashani, cardiologist, Lung Transplantation Research Center, National Research Institute of Tuberculosis and Lung Disease (NRITLD), Shahid Beheshti University of Medical Science, Tehran, Iran.; Principal Investigator: Paritash Tahmaseb pour, MD, MD

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Anticipated): August 1, 2013
• Study Completion (Anticipated): August 1, 2013

Study Registration Dates

• First Submitted: September 1, 2012
• First Submitted That Met QC Criteria: September 11, 2012
• First Posted (Estimate): September 12, 2012

Study Record Updates

• Last Update Posted (Estimate): August 12, 2013
• Last Update Submitted That Met QC Criteria: August 8, 2013
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Keywords: Quality of Life; Exercise Capacity; Idiopathic Pulmonary Arterial Hypertension; Eisenmenger Syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Disease; Congenital Abnormalities; Hypertension, Pulmonary; Heart Defects, Congenital; Cardiovascular Abnormalities; Hypertension; Syndrome; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Eisenmenger Complex
• Other Study ID Numbers: f-91-138