Idiopathic Pulmonary Arterial HypertensionEarly Phase 1NCT01683981
Exercise Capacity and Quality of Life in Patients With PPH Receiving Short Term Oral L-Citrulline Malate
A Early Phase 1 study testing L-Citrulline Malate in people with Idiopathic Pulmonary Arterial Hypertension and Eisenmenger Syndrome, run by Masih Daneshvari Hospital at 1 site in Iran.
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. Read more about this study
- Who is it for?
- Ages 15 to 70 years
- Conditions the study is for
- Idiopathic Pulmonary Arterial Hypertension, Eisenmenger Syndrome
- What is being tested?
- L-Citrulline Malate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteIran
- Study dates
- Aug 2012to Aug 2013
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 15 to 70 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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,
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- pregnancy,
- lack of family support,
- psychosocial problems,
- drug or alcohol abuse, and
- noncompliance with established medical protocol.
Trial locations and contacts
1 site in 1 country.
Iran1 site, 1 recruiting
- Recruiting
MasihDH
Tehran, 021
babak sharif kashani, cardiologist, 0098-02188883114, sharifk@nritld.ac.ir
paritash tahmasebpour, MD, 0098-09125037861, paritash_t@yahoo.com
About this study
Official title: 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.
Read the 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).
- Being tested
- L-Citrulline Malate
- Keywords
- Idiopathic Pulmonary Arterial Hypertension, Eisenmenger Syndrome, Exercise Capacity, Quality of Life
- Medical subject headings
- Familial Primary Pulmonary Hypertension, Eisenmenger Complex
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
L-Citrulline MalateDrug
Also called Stimol
3 gr per day, oral, for 2 weeks
| Study group | Role | What they receive |
|---|---|---|
| L-Citrulline, Exercise Capacity | Experimental | L-Citrulline malate, 1gr, oral, divided 3 times a day,for 2 weeks Receives: Drug: L-Citrulline Malate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 2 weeks
Secondary outcomes (1)
changes in mean pulmonary-artery pressure
changes in mean pulmonary-artery pressure from baseline to week 2.
Measured: 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Sep 2012 (estimated)
- Study startAug 2012
- Primary completionAug 2013 (estimated)
- Study completionAug 2013 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Idiopathic Pulmonary Arterial HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Masih Daneshvari Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, babak sharif kashani, Masih Daneshvari Hospital
- Investigators
- babak sharif kashani, cardiologist, 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, Principal investigator, MD
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01683981
- Sponsor's protocol ID
- f-91-138
- Status last verified
- Sep 2012
- First submitted
- 1 Sep 2012
- Last updated
- 12 Aug 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Exercise Capacity and Quality of Life in Patients With Idiopathic Pulmonary Hypertension and Eisenmenger Syndrome Receiving Short Term Oral L-Citrulline Malate
- ClinicalTrials.gov ID
- NCT01683981
- Acronym / sponsor ID
- f-91-138
- Keywords
- Idiopathic Pulmonary Arterial Hypertension, Eisenmenger Syndrome, Exercise Capacity, Quality of Life
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- Masih Daneshvari HospitalUniversity, hospital or other
- Study start
- Aug 2012
- Primary completion
- Aug 2013 (estimated)
- Study completion
- Aug 2013 (estimated)
- First posted
- 12 Sep 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| L-Citrulline, Exercise Capacity | Experimental | Drug: L-Citrulline MalateL-Citrulline malate, 1gr, oral, divided 3 times a day,for 2 weeks |
Who may qualify
- Ages
- 15 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- 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).
Key exclusion criteria (11 listed)
- 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,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| L-Citrulline MalateAlso: Stimol3 gr per day, oral, for 2 weeks | Drug | L-Citrulline, Exercise Capacity |
Primary outcome
the change in exercise capacity
Time frame: 2 weeks
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)
1 secondary outcome
changes in mean pulmonary-artery pressure
Time frame: 2 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2013.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
babak sharif kashani, cardiologist 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 principal investigator
MD
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing L-Citrulline Malate in people with Idiopathic Pulmonary Arterial Hypertension and Eisenmenger Syndrome, run by Masih Daneshvari Hospital at 1 site in Iran.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 12 Aug 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Iran. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact babak sharif kashani, Cardiologist (0098-02188883114, sharifk@nritld.ac.ir), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
the change in exercise capacity (time frame: 2 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Aug 2013.