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

Idiopathic Pulmonary Arterial Hypertension Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01683981
• Other study ID #: f-91-138
• Status: Recruiting
• Phase: Phase 0
• First received: September 1, 2012
• Last updated: August 8, 2013
• Start date: August 2012
• Est. completion date: August 2013

Study information

• Verified date: September 2012
• Source: Masih Daneshvari Hospital
• Contact: babak sharif kashani, Cardiologist
• Phone: 0098-02188883114
• Email: sharifk[@]nritld.ac.ir
• Is FDA regulated: No
• Health authority: Iran: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 25
• Est. completion date: August 2013
• Est. primary completion date: August 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 15 Years to 70 Years

Eligibility

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 Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Eisenmenger Complex
• Eisenmenger Syndrome
• Hypertension
• Idiopathic Pulmonary Arterial Hypertension

Intervention

Drug:
• L-Citrulline Malate
3 gr per day, oral, for 2 weeks

Locations

Country	Name	City	State
Iran, Islamic Republic of	MasihDH	Tehran

Sponsors (1)

Lead Sponsor	Collaborator
Masih Daneshvari Hospital

Country where clinical trial is conducted

Iran, Islamic Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	change in the quality of life	change in the quality of life from baseline to week 2	2 weeks	No
Primary	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	No
Secondary	changes in mean pulmonary-artery pressure	changes in mean pulmonary-artery pressure from baseline to week 2.	2 weeks	No