Critically IllPhase 4ImmunolargNCT01038622
Directed Immuno Nutrition by L-arginine for Critically Ill Patients
A Phase 4 study testing L-arginine in people with Critically Ill, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
The main objective of this proof-of-concept study is to demonstrate that the only administration of L-arginine, based on a suspected deficit monitored by nasal nitric oxide measurement, can improve immune functions in critically ill patients at high risk of nosocomial infection. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Critically Ill
- What is being tested?
- L-arginine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteFrance
- Study dates
- Nov 2009to Jan 2011
- Phase
- Phase 4
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- age > 18 years
- medical patient (absence of recent surgery or trauma)
- initial aggression < 5 days
- mechanically ventilated with expected duration of mechanical ventilation > 2 days
- enteral nutrition
- absence of previous immunosuppression
- nasal NO on day 1 of ICU stay < 60 ppb
Who cannot join
- severe sepsis
- septic shock
- condition associated with a decreased nasal NO concentration (cystic fibrosis, nasal polyposis, primary ciliary dyskinesia
- pregnancy
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Randomized Directed Immuno Nutrition by L-arginine for Critically Ill Patients
The main objective of this proof-of-concept study is to demonstrate that the only administration of L-arginine, based on a suspected deficit monitored by nasal nitric oxide measurement, can improve immune functions in critically ill patients at high risk of nosocomial infection.
Read the detailed description
Background : A meta-analysis has demonstrated the beneficial effect of immuno nutrition in surgical patients, leading to half reduction of incidence of nosocomial infections (HEYLAND DK, JAMA ; 2001). This beneficial effect seems to be related to L-arginine content of formula. In medical intensive care, such an improvement has not been shown, in spite of similar impairment of immune response, which could be due to a more heterogenous population. Our hypothesis is that this beneficial effect could be observed in selected patients of medical intensive care units. L-arginine is a semi-essential amino acid that is the precursor of nitric oxide (NO) synthesis. NO is involved in immune response regulation and has antimicrobial properties, notably into airways where it can be measured in exhaled gas. A decrease in exhaled and nasal NO has been demonstrated in critically ill patients, which may suggest an impairment of its production.
Objectives : The aim of this study is to evaluate the immune effects of enteral L-arginine administration in non surgical critically ill patients. These patients will be selected based on the decrease in nasal NO: directed immuno nutrition. The main objective is to demonstrate that L-arginine administration, as compared to placebo administration, increases nasal NO and enhances immune functions (increase in HLA-DR expression on monocytes, modification of circulating Myeloid-Derived Suppressor Cells (MDSC), decrease in IL-6, IL-17 plasmatic concentrations): stimulation of immune response. The secondary objective is to demonstrate the safety of L-arginine administration on organ failure and on the incidence of nosocomial infections.
This is a monocentric therapeutic trial, randomized and double blind: standard enteral nutrition plus L-arginine (200 mg/kg/d for 5 days from the admission in ICU) versus standard enteral nutrition plus placebo.
Methods-Patients: Non surgical patients admitted in a single medical intensive care unit, under mechanical ventilation for an expected duration > 2 days, with decreased concentrations of nasal NO (< 60 ppb), without severe sepsis or septic shock, will be enrolled. On admission (before treatment), the severity will be evaluated (SAPS II and SOFA score) together with an assessment of plasmatic L-arginine, cytokines (IL-6, IL-17), MDSC, and expression of HLA-DR by monocytes. The same evaluation will be repeated on day 4 (during treatment) and on day 7 (after treatment). The enrolment of 50 patients is statistically enough to demonstrate an increased expression of HLA-DR in the L-arginine group as compared to the placebo group on day 4.
Expected results and perspectives: The aim of this study is to demonstrate the validity of the concept of directed immune stimulation by the sole L-arginine in medical intensive care unit, the patients being selected based on their decrease in exhaled and nasal NO concentrations. This pathophysiological study is the necessary first step before conducting a large clinical trial aimed at demonstrating a reduction of nosocomial infection incidence by L-arginine.
- Conditions
- Critically Ill
- Being tested
- L-arginine, placebo
- Keywords
- L-arginine, Nasal NO, Nosocomial infection, Immune function, HLA-DR expression, Critically ill, Medical ICU patients
- Medical subject headings
- Critical Illness, Cross Infection
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
L-arginineDrug
5-day L-arginine treatment
placeboDrug
5-day placebo treatment
| Study group | Role | What they receive |
|---|---|---|
| L-arginine | Active comparator | 5-day L-arginine treatment (200 mg/kg) Receives: Drug: L-arginine |
| placebo | Placebo comparator | 5-day placebo treatment Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Expression of HLA-DR in the L-arginine group as compared to the placebo group
Measured: on day 3
Secondary outcomes (3)
HLA-DR on day 7, IL-10 and IL-17 on day 3 and 7, MDSC on day 3 and 7
Measured: on day 3 and on day 7
Nosocomial infections
Measured: in the first 15 days
Safety issue: organ failure score (SOFA score) on day 3 and 7; issue from ICU
Measured: on day 3 and 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2009 (estimated)
- Study startNov 2009
- Primary completionNov 2010
- Study completionJan 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Critically IllStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- 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
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jean Marc TADIE, MD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01038622
- Sponsor's protocol ID
- P090203
- Acronym
- Immunolarg
- Status last verified
- Dec 2009
- First submitted
- 22 Dec 2009
- Last updated
- 18 Sep 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
Marik PE, Zaloga GP. Immunonutrition in critically ill patients: a systematic review and analysis of the literature. Intensive Care Med. 2008 Nov;34(11):1980-90. doi: 10.1007/s00134-008-1213-6. Epub 2008 Jul 15.
PubMed 18626628Tadie JM, Cynober L, Peigne V, Caumont-Prim A, Neveux N, Gey A, Guerot E, Diehl JL, Fagon JY, Tartour E, Delclaux C. Arginine administration to critically ill patients with a low nitric oxide fraction in the airways: a pilot study. Intensive Care Med. 2013 Sep;39(9):1663-5. doi: 10.1007/s00134-013-2984-y. Epub 2013 Jun 19. No abstract available.
PubMed 23778831
Study at a glance
From the registry record, last updated by the sponsor on 18 Sep 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Directed Immuno Nutrition by L-arginine for Critically Ill Patients
- ClinicalTrials.gov ID
- NCT01038622
- Acronym / sponsor ID
- Immunolarg / P090203
- Conditions
- Critically Ill
- Keywords
- L-arginine, Nasal NO, Nosocomial infection, Immune function, HLA-DR expression, Critically ill, Medical ICU patients
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Nov 2009
- Primary completion
- Nov 2010 (actual)
- Study completion
- Jan 2011 (actual)
- First posted
- 24 Dec 2009 (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.
The main objective of this proof-of-concept study is to demonstrate that the only administration of L-arginine, based on a suspected deficit monitored by nasal nitric oxide measurement, can improve immune functions in critically ill patients at high risk of nosocomial infection.
Detailed description
Background : A meta-analysis has demonstrated the beneficial effect of immuno nutrition in surgical patients, leading to half reduction of incidence of nosocomial infections (HEYLAND DK, JAMA ; 2001). This beneficial effect seems to be related to L-arginine content of formula. In medical intensive care, such an improvement has not been shown, in spite of similar impairment of immune response, which could be due to a more heterogenous population. Our hypothesis is that this beneficial effect could be observed in selected patients of medical intensive care units. L-arginine is a semi-essential amino acid that is the precursor of nitric oxide (NO) synthesis. NO is involved in immune response regulation and has antimicrobial properties, notably into airways where it can be measured in exhaled gas. A decrease in exhaled and nasal NO has been demonstrated in critically ill patients, which may suggest an impairment of its production.
Objectives : The aim of this study is to evaluate the immune effects of enteral L-arginine administration in non surgical critically ill patients. These patients will be selected based on the decrease in nasal NO: directed immuno nutrition. The main objective is to demonstrate that L-arginine administration, as compared to placebo administration, increases nasal NO and enhances immune functions (increase in HLA-DR expression on monocytes, modification of circulating Myeloid-Derived Suppressor Cells (MDSC), decrease in IL-6, IL-17 plasmatic concentrations): stimulation of immune response. The secondary objective is to demonstrate the safety of L-arginine administration on organ failure and on the incidence of nosocomial infections.
This is a monocentric therapeutic trial, randomized and double blind: standard enteral nutrition plus L-arginine (200 mg/kg/d for 5 days from the admission in ICU) versus standard enteral nutrition plus placebo.
Methods-Patients: Non surgical patients admitted in a single medical intensive care unit, under mechanical ventilation for an expected duration > 2 days, with decreased concentrations of nasal NO (< 60 ppb), without severe sepsis or septic shock, will be enrolled. On admission (before treatment), the severity will be evaluated (SAPS II and SOFA score) together with an assessment of plasmatic L-arginine, cytokines (IL-6, IL-17), MDSC, and expression of HLA-DR by monocytes. The same evaluation will be repeated on day 4 (during treatment) and on day 7 (after treatment). The enrolment of 50 patients is statistically enough to demonstrate an increased expression of HLA-DR in the L-arginine group as compared to the placebo group on day 4.
Expected results and perspectives: The aim of this study is to demonstrate the validity of the concept of directed immune stimulation by the sole L-arginine in medical intensive care unit, the patients being selected based on their decrease in exhaled and nasal NO concentrations. This pathophysiological study is the necessary first step before conducting a large clinical trial aimed at demonstrating a reduction of nosocomial infection incidence by L-arginine.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| L-arginine | Active comparator | Drug: L-arginine5-day L-arginine treatment (200 mg/kg) |
| placebo | Placebo comparator | Drug: placebo5-day placebo treatment |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- age > 18 years
- medical patient (absence of recent surgery or trauma)
- initial aggression < 5 days
- mechanically ventilated with expected duration of mechanical ventilation > 2 days
- enteral nutrition
Key exclusion criteria (4 listed)
- severe sepsis
- septic shock
- condition associated with a decreased nasal NO concentration (cystic fibrosis, nasal polyposis, primary ciliary dyskinesia
- pregnancy
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-arginine5-day L-arginine treatment | Drug | L-arginine |
| placebo5-day placebo treatment | Drug | placebo |
Primary outcome
Expression of HLA-DR in the L-arginine group as compared to the placebo group
Time frame: on day 3
3 secondary outcomes
HLA-DR on day 7, IL-10 and IL-17 on day 3 and 7, MDSC on day 3 and 7
Time frame: on day 3 and on day 7
Nosocomial infections
Time frame: in the first 15 days
Safety issue: organ failure score (SOFA score) on day 3 and 7; issue from ICU
Time frame: on day 3 and 7
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2013.
- Results publication: PubMed 18626628Marik PE, Zaloga GP. Immunonutrition in critically ill patients: a systematic review and analysis of the literature. Intensive Care Med. 2008 Nov;34(11):1980-90. doi: 10.1007/s00134-008-1213-6. Epub 2008 Jul 15.
- Derived from this study: PubMed 23778831Tadie JM, Cynober L, Peigne V, Caumont-Prim A, Neveux N, Gey A, Guerot E, Diehl JL, Fagon JY, Tartour E, Delclaux C. Arginine administration to critically ill patients with a low nitric oxide fraction in the airways: a pilot study. Intensive Care Med. 2013 Sep;39(9):1663-5. doi: 10.1007/s00134-013-2984-y. Epub 2013 Jun 19. No abstract available.
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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.
Jean Marc TADIE, MD principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing L-arginine in people with Critically Ill, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 7 inclusion and 4 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: finished, as of the sponsor's last update on 18 Sep 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 France. 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. Some participants in this study may receive a placebo. 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?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Expression of HLA-DR in the L-arginine group as compared to the placebo group (time frame: on day 3). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01038622, which also lists 2 linked publications.
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 18 Sep 2013.