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Severe Chronic Respiratory Failure and Citrulline

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ClinicalTrials.gov Identifier: NCT03694964
Recruitment Status : Not yet recruiting
First Posted : October 3, 2018
Last Update Posted : October 3, 2018
Sponsor:
Information provided by (Responsible Party):
University Hospital, Grenoble

Brief Summary:

Because of its very high bioavailability and its specific and direct action on protein synthesis, the investigators hypothesize that citrulline supplementation would be an innovative nutritional strategy to improve the peripheral muscle mass and strength in COPD patients with severe chronic respiratory failure.

This supplementation would be more effective if the pathology is severe and the chronic systemic inflammation important. The benefits of this supplementation could help the most severe patients break out of the cycle of inactivity and thus optimize their quality of life.

The main objective of this study is to evaluate the impact of 45-day nutritional supplementation with Citrulline (10 g / day) on the body composition (lean body mass) in malnourished COPD patients with severe chronic respiratory failure.


Condition or disease Intervention/treatment Phase
Pulmonary Disease, Chronic Obstructive Drug: ProteoCIT® Drug: Placebo Oral Tablet Not Applicable

Detailed Description:

Denutrition in patients with COPD (Chronic Obstructive Pulmonary Disease) is characterized by muscle atrophy and loss of strength in the lower extremities. It worsens the symptomatology, exercise intolerance, impaired quality of life and prognosis of patients.

Consequence of a protein deficiency associated with systemic inflammation, denutrition is becoming increasingly important in patients with chronic respiratory failure (CRF). L-citrulline is an amino acid having a direct action on muscle protein synthesis. The citrulline supplementation is an effective treatment to fight against muscle loss in aging subjects. Its impact on the functional and nutritional status of COPD patients has not been studied.

Our main objective is to determine the impact of supplementation with Citrulline on mass and peripheral muscle strength in COPD with CRF. Our secondary objectives are to identify whether these benefits are dependent on the severity of the disease and if they are associated with increased physical activity, exercise tolerance and an improvement in symptoms and quality of life. This prospective, randomized, controlled, double-blind study will include 60 stable COPD patients (stage 3 and 4), with long-term oxygen therapy and / or non-invasive ventilation, BMI <25 kg.m2 and suspicion of sarcopenia.

For 45 days, patients will receive either citrulline (ProteoCIT®, 10mg) or placebo. The severity of COPD will be assessed by spirometry and blood gas data, the BODE index, exacerbations, comorbidities, nutritional status and systemic inflammation (CRPs, Fibrinogens). the investigators will evaluate before and after supplementation: body composition (DEXA), quadriceps strength and grip strength, walking speed, the exercise tolerance (6MWD), dyspnea (MMRC scales, BDI / TDI), quality of life (CAT and VSRQ questionnaires). Physical activity will be assessed by continuous actigraphy. This multicenter study will be conducted in 3 French hospitals: Grenoble, Nancy, Dijon.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: After signing the informed consent form, the patients will be randomized either in the experimental group (Citrulline (ProteiCIT®): 10 g / day) or in the control group (placebo).
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: Double blind study: treatment (experimental group) vs placebo (control group).
Primary Purpose: Treatment
Official Title: Effects of Oral Citrulline Supplementation in Sarcopenia for Patients With Severe Chronic Respiratory Failure by COPD
Estimated Study Start Date : January 2019
Estimated Primary Completion Date : January 2019
Estimated Study Completion Date : July 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Supplementation with Citrulline
Patients will receive citrulline (ProteoCIT®) 10 mg by day during 45 days
Drug: ProteoCIT®
30 patients will be randomized into the group that will receive 10 mg of citrulline and 30 patients will be randomized into the placebo group for 45 days

Placebo Comparator: Placebo
Patients will receive placebo (one tablet by day) during 45 days
Drug: Placebo Oral Tablet
30 patients will be randomized into the group that will receive 10 mg of citrulline and 30 patients will be randomized into the placebo group for 45 days




Primary Outcome Measures :
  1. Impact of a 45-day nutritional supplementation with Citrulline (10 g / day) on body composition (lean body mass) of malnourished patients with COPD and severe chronic respiratory failure [ Time Frame: 45 days ]
    Lean mass (kg.m-2) measured by DEXA


Secondary Outcome Measures :
  1. Impact of a nutritional supplementation with Citrulline on body composition [ Time Frame: 45 days ]
    Regional variations of fat and bone mass measured by DEXA

  2. Impact of a nutritional supplementation with Citrulline on muscular force [ Time Frame: 45 days ]
    Grip force, Maximum strength of the quadriceps

  3. Impact of a nutritional supplementation with Citrulline on tolerance to effort [ Time Frame: 45 days ]
    3 min chair test

  4. Impact of a nutritional supplementation with Citrulline on BODE stage [ Time Frame: 45 days ]
    BODE score - The BODE score is composed of the following parameters: the body mass index, the post-bronchodilator FEV1 expressed as a percentage of the theoretical values (airflow obstruction), the dyspnoea score measured by the modified scale of the RCM ( Dyspnea) and the distance in meters traveled during a 6-minute walk test (Exercise).Each value of each parmeter corresponds to 1 point (from 0 to 4) and we add everything. The results are: score 0 to 2: mortality 15% at 4 years; and score 7 to 10: 80% mortality at 4 years

  5. Impact of a nutritional supplementation with Citrulline on inflammation and nutritional status [ Time Frame: 45 days ]
    BMI

  6. Impact of a nutritional supplementation with Citrulline on quality of life and dyspnea [ Time Frame: 45 days ]
    Quality of life questionaries: COPD assessement Test (CAT): the participants answers differents questions that make it possible to measure the state of health of the patient.

  7. Impact of a nutritional supplementation with Citrulline on physical activity [ Time Frame: 45 days ]
    Actigraphy

  8. Impact of a nutritional supplementation with Citrulline on tolerance to effort [ Time Frame: 45 days ]
    Pulmonary function test

  9. Impact of a nutritional supplementation with Citrulline on tolerance to effort [ Time Frame: 45 days ]
    Exacerbation number

  10. Impact of a nutritional supplementation with Citrulline on tolerance to effort [ Time Frame: 45 days ]
    Comorbidities

  11. Impact of a nutritional supplementation with Citrulline on tolerance to effort [ Time Frame: 45 days ]
    Blood gas results

  12. Impact of a nutritional supplementation with Citrulline on quality of life and dyspnea [ Time Frame: 45 days ]
    Quality of life questionaries: Visual Simplified respiratory questionary (VSRQ)

  13. Impact of a nutritional supplementation with Citrulline on quality of life and dyspnea [ Time Frame: 45 days ]
    Quality of life questionaries: Medical Research Council (mMRC)

  14. Impact of a nutritional supplementation with Citrulline on quality of life and dyspnea [ Time Frame: 45 days ]
    Quality of life questionaries: The baseline and Transition Dyspnea Indices (TDI/BDI scale)

  15. Impact of a nutritional supplementation with Citrulline on quality of life and dyspnea [ Time Frame: 45 days ]
    Quality of life questionaries: Disability Related to COPD tool (DIRECT) : a self-administered questionnaire designed to evaluate the impact of COPD on the patient's daily activities

  16. Impact of a nutritional supplementation with Citrulline on inflammation and nutritional status [ Time Frame: 45 days ]
    MNA test : Mini Nutritional Assessment

  17. Impact of a nutritional supplementation with Citrulline on inflammation and nutritional status [ Time Frame: 45 days ]
    a blood sample will be taken from the participants to measure the effects of citrulline on the inflammation and nutritional status of the patient. C reactive protein (CRPus), inflammation marker

  18. Impact of a nutritional supplementation with Citrulline on inflammation and nutritional status [ Time Frame: 45 days ]
    Fibrinogen : inflammation marker that will be measured on a blood sample.

  19. Impact of a nutritional supplementation with Citrulline on inflammation and nutritional status [ Time Frame: 45 days ]
    Transthyretinemia biological parameter that will measure the nutritional status of the patient.will be mesasured on blood sample.

  20. Impact of a nutritional supplementation with Citrulline on inflammation and nutritional status [ Time Frame: 45 days ]
    Albuminemia : biological parameter that will measure the nutritional status of the patient.will be mesasured on blood sample.

  21. Impact of a nutritional supplementation with Citrulline on inflammation and nutritional status [ Time Frame: 45 days ]
    glycemia biological parameter that will measure the nutritional status of the patient.will be mesasured on blood sample.

  22. Impact of a nutritional supplementation with Citrulline on inflammation and nutritional status [ Time Frame: 45 days ]
    Insulinemia biological parameter that will measure the nutritional status of the patient. will be mesasured on blood sample.

  23. Impact of a nutritional supplementation with Citrulline on inflammation and nutritional status [ Time Frame: 45 days ]
    Acid-aminemia biological parameter that will measure the nutritional status of the patient. will be mesasured on blood sample.

  24. Impact of a nutritional supplementation with Citrulline on inflammation and nutritional status [ Time Frame: 45 days ]
    3 MethylHistine / urinary creatinine : this biological parameter will be measure on the urine: biological parameter measured on the urine. which will help to highlight the nutritional status of the patient.



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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • COPD Gold III and IV
  • involuntary decrease in weight ≥ 5% in the last 6 months,
  • BMI < 25 kg.m²
  • suspicion of sarcopenia marked by a score higher than 4 on the SARC-F questionnaire
  • clinical stability defined by no exacerbation requiring hospitalization for at least 3 months
  • long-term oxygen therapy (≥ 12h / day) and / or non-invasive ventilation for at least 6 months
  • At least one exacerbation requiring hospitalization in the year before inclusion.
  • Informed consent written

Exclusion Criteria:

  • Restrictive or mixed respiratory disease.
  • Long-term systemic corticosteroids (> 6 months per year)
  • Severe and terminal renal failure (creatinine clearance <30ml / min)
  • Patients with severe hypotension, uncontrolled hypertension
  • Contraindication to taking citrulline: anticoagulant and anticancer chemotherapy
  • Osmotic diarrhea
  • Taking food supplements whatever its form.
  • Severe and / or unbalanced progressive disease that may be life-threatening in the medium term,
  • Proven psychiatric pathology (schizophrenia type, dementia, bipolar / severe psychotic disorders, severe depressive syndrome),
  • Cognitive or psychomotor problem that limit the realization and understanding of the different evaluations,
  • Simultaneous participation in another research involving the human person
  • Pregnant, parturient or breastfeeding women
  • deprivation of liberty by judicial or administrative decision, protection by law, under the protection of justice, under guardianship or trusteeship,
  • No affiliation to a social security scheme.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03694964


Contacts
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Contact: CHRISTOPHE PISON, MD PHD +33(0)4 76 76 54 53 CPISON@CHU-GRENOBLE.FR
Contact: ANAIS ADOLLE AADOLLE@CHU-GRENOBLE.FR

Locations
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France
Hôpital François Mitterrand - CHU de Dijon
Dijon, France
Hôpitaux de Brabois - CHU de Nancy
Nancy, France
Sponsors and Collaborators
University Hospital, Grenoble
Investigators
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Principal Investigator: CHRISTOPHE PISON University Hospital, Grenoble

Publications:
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Responsible Party: University Hospital, Grenoble
ClinicalTrials.gov Identifier: NCT03694964     History of Changes
Other Study ID Numbers: 38RC17.310
First Posted: October 3, 2018    Key Record Dates
Last Update Posted: October 3, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University Hospital, Grenoble:
Pulmonary Disease, Chronic Obstructive
Sarcopenia
Citrulline
Body composition
Denutrition

Additional relevant MeSH terms:
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Lung Diseases
Respiratory Insufficiency
Chronic Disease
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Diseases
Respiration Disorders
Disease Attributes
Pathologic Processes
Lung Diseases, Obstructive