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

NCT ID: NCT01683981

Last Updated: 2013-08-12

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-08-31
• Study Completion Date: 2013-08-31

Brief Summary

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.

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).

Conditions

Idiopathic Pulmonary Arterial Hypertension; Eisenmenger Syndrome

Keywords

Idiopathic Pulmonary Arterial Hypertension; Eisenmenger Syndrome; Exercise Capacity; Quality of Life

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Blinding Strategy: NONE

Study Groups

L-Citrulline, Exercise Capacity

L-Citrulline malate, 1gr, oral, divided 3 times a day,for 2 weeks

Group Type: EXPERIMENTAL

L-Citrulline Malate

Intervention Type: DRUG

3 gr per day, oral, for 2 weeks

Interventions

L-Citrulline Malate

3 gr per day, oral, for 2 weeks

Intervention Type: DRUG

Other Intervention Names

Stimol

Eligibility 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.

• Minimum Eligible Age: 15 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Masih Daneshvari Hospital

OTHER

Sponsor Role: lead

Responsible Party

babak sharif kashani

Head of Cardiology Department of NRITLD, Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

babak sharif kashani, cardiologist

Role: PRINCIPAL_INVESTIGATOR

Lung Transplantation Research Center, National Research Institute of Tuberculosis and Lung Disease (NRITLD), Shahid Beheshti University of Medical Science, Tehran, Iran.

Paritash Tahmaseb pour, MD

Role: PRINCIPAL_INVESTIGATOR

MD

Locations

MasihDH

Tehran, , Iran

Site Status: RECRUITING

Countries

Iran

Central Contacts

babak sharif kashani, Cardiologist

Role: CONTACT

Phone: 0098-02188883114

Email: sharifk@nritld.ac.ir

paritash tahmasebpour, MD

Role: CONTACT

Phone: 0098-09125037861

Email: paritash_t@yahoo.com

Facility Contacts

babak sharif kashani, cardiologist

Role: primary

paritash tahmasebpour, MD

Role: backup

Other Identifiers

f-91-138

Identifier Type: -

Identifier Source: org_study_id