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

This study is currently recruiting participants.
Verified September 2012 by Masih Daneshvari Hospital
Sponsor:
Information provided by (Responsible Party):
babak sharif kashani, Masih Daneshvari Hospital
ClinicalTrials.gov Identifier:
NCT01683981
First received: September 1, 2012
Last updated: August 8, 2013
Last verified: September 2012
  Purpose

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.


Condition Intervention Phase
Idiopathic Pulmonary Arterial Hypertension
Eisenmenger Syndrome
Drug: L-Citrulline Malate
Phase 0

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: Exercise Capacity and Quality of Life in Patients With Idiopathic Pulmonary Hypertension and Eisenmenger Syndrome Receiving Short Term Oral L-Citrulline Malate

Resource links provided by NLM:


Further study details as provided by Masih Daneshvari Hospital:

Primary Outcome Measures:
  • the change in exercise capacity [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
    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)


Secondary Outcome Measures:
  • changes in mean pulmonary-artery pressure [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
    changes in mean pulmonary-artery pressure from baseline to week 2.


Other Outcome Measures:
  • change in the quality of life [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
    change in the quality of life from baseline to week 2


Estimated Enrollment: 25
Study Start Date: August 2012
Estimated Study Completion Date: August 2013
Estimated Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Stimol

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).

  Eligibility

Ages Eligible for Study:   15 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01683981

Contacts
Contact: babak sharif kashani, Cardiologist 0098-02188883114 sharifk@nritld.ac.ir
Contact: paritash tahmasebpour, MD 0098-09125037861 paritash_t@yahoo.com

Locations
Iran, Islamic Republic of
MasihDH Recruiting
Tehran, Iran, Islamic Republic of, 021
Contact: babak sharif kashani, cardiologist    0098-02188883114    sharifk@nritld.ac.ir   
Contact: paritash tahmasebpour, MD    0098-09125037861    paritash_t@yahoo.com   
Principal Investigator: babak sharif kashani, cardiologist         
Sponsors and Collaborators
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
  More Information

No publications provided

Responsible Party: babak sharif kashani, Head of Cardiology Department of NRITLD, Associate Professor, Masih Daneshvari Hospital
ClinicalTrials.gov Identifier: NCT01683981     History of Changes
Other Study ID Numbers: f-91-138
Study First Received: September 1, 2012
Last Updated: August 8, 2013
Health Authority: Iran: Ethics Committee

Keywords provided by Masih Daneshvari Hospital:
Idiopathic Pulmonary Arterial Hypertension
Eisenmenger Syndrome
Exercise Capacity
Quality of Life

Additional relevant MeSH terms:
Hypertension, Pulmonary
Eisenmenger Complex
Hypertension
Lung Diseases
Respiratory Tract Diseases
Heart Defects, Congenital
Cardiovascular Abnormalities
Cardiovascular Diseases
Heart Diseases
Congenital Abnormalities
Vascular Diseases

ClinicalTrials.gov processed this record on April 17, 2014