Chronic Obstructive Pulmonary Disease SeverePhase 3CITRUSNCT06212765
Oral Citrulline Supplementation in COPD Patients With Malnutrition
A Phase 3 study testing L-citrulline in people with Chronic Obstructive Pulmonary Disease Severe and Malnutrition, run by University Hospital, Grenoble.
Trial summary
Chronic obstructive pulmonary disease (COPD) is complicated by malnutrition in 20-70% of cases. In COPD, low fat-free mass is associated with a higher risk of morbidity and mortality. L-citrulline is a non-protein amino acid that has a direct effect on muscle protein synthesis. Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Chronic Obstructive Pulmonary Disease Severe, Malnutrition
- What is being tested?
- L-citrulline
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- No sites listed yet
- Study dates
- 25 Jan 2024to 25 Sep 2026
- Phase
- Phase 3
- 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 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men and women aged 50 and over
- COPD stage 3 or 4 according to GOLD criteria
- BMI < 20 kg/m2 if < 70 years old or < 22 kg/m2 if ≥ 70 years old
- Suspicion of sarcopenia marked by a score of 4 or more on the SARC-F questionnaire
- Absence of severe COPD exacerbation for at least 3 months
Who cannot join
- Main respiratory disease other than COPD
- Daily long-term use of systemic corticosteroids (>6 months per year, whatever the dose)
- Severe and end-stage renal insufficiency (creatinine clearance <30ml/min)
- Patient with severe hypotension, uncontrolled hypertension (at investigator's discretion)
- Contraindication to L-citrulline intake: VKA and/or cancer chemotherapy
- Osmotic diarrhoea
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- Severe and/or uncontrolled progressive pathology likely to be life-threatening
- Psychiatric pathology (schizophrenia, dementia, severe bipolar/psychotic disorders, severe depressive syndrome)
- Pacemaker or other implanted electronic device
Trial locations and contacts
No sites are listed yet.
Samarmar Chacaroun, PhD contact
About this study
Official title: Effects of Oral Citrulline Supplementation on Fat-free Mass in COPD Patients With Malnutrition
Chronic obstructive pulmonary disease (COPD) is complicated by malnutrition in 20-70% of cases. In COPD, low fat-free mass is associated with a higher risk of morbidity and mortality. L-citrulline is a non-protein amino acid that has a direct effect on muscle protein synthesis. Oral supplementation with L-citrulline (10 g/day) in malnourished patients has shown to increase fat-free mass. The effects of L-citrulline supplementation in malnourished COPD patients are unknown.
The main objective of this prospective, single-centre, randomised, double-blind, placebo-controlled study will be to determine the impact of 45 days of nutritional supplementation with L-citrulline (10 g/day) on lean body mass (fat-free mass index (in kg.m-2) measured by bioelectrical impedance analysis) in malnourished patients (BMI < 20 kg/m2 if < 70 years old or < 22 kg/m2 if ≥ 70 years old) with COPD at stages 3-4 of the GOLD classification.
- Being tested
- L-citrulline
- Keywords
- COPD, L-citrulline, Malnutrition
- Medical subject headings
- Malnutrition, Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
L-citrullineDrug
to take 1 pod a day for 45 days
| Study group | Role | What they receive |
|---|---|---|
| Citrulline | Experimental | The experimental product is 100% L-citrulline. Each pod will contain 10 grams of L-citrulline. Ten grams of L-citrulline provide 2.4 g of nitrogen. Receives: Drug: L-citrulline |
| Standard care | Active comparator | The active comparator is a mixture of the six non-essential amino acids. In order for the active comparator to be iso-nitrogenated compared with the experimental product, it will provide 2.4 g of nitrogen per pod. The active comparator will combine 13.2 % alanine, 19.8 % aspartate, 11.2 % glycine, 17.1 % proline, 15.6 % serine and 23.1 % histidine, for a total of 13 g of amino acids per pod. Receives: Drug: L-citrulline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fat Free Mass Index
Fat Free Mass Index (in kg.m-2) measured by bioelectrical impedance analysis
Measured: baseline, 45+/-5 day and 1 year +/- 2 weeks
Secondary outcomes (11)
Grip strength
Grip strength will be measured using a dynamometer with the patient in a seated position, elbow bent at 90°, shoulders relaxed and forearm in a neutral position. The dynamometer should be held in the dominant hand. The measurement should be taken twice. The highest value will be used.
Measured: baseline, 45+/-5 day and 1 year +/- 2 weeks
Maximum quadriceps strength
The maximum voluntary force of the quadriceps of the left lower limb will be measured on a weight bench using a strain gauge to determine force during isometric contraction (at 90° knee flexion). The position of the patient will be standardized: arms crossed over the chest, no back support during the measurement and no support of the hips and contralateral leg to avoid any compensatory movement. Three reproducible measurements (+/-10%) will be taken at 1 min intervals, with the highest value selected.
Measured: baseline, 45+/-5 day and 1 year +/- 2 weeks
6-minute walk test
The 6-min walking test (6MWT) measures the distance that a patient can walk on an indoor 30-m flat corridor for a 6-min period. Due to a familiarisation effect, two tests will be performed, with at least 15 min of intervening rest, with the greatest distance in the two tests being recorded. The 6-min walking distance (6MWD) will be expressed in metres. Other variables will be measured: minimum pulse oxygen saturation (SpO2), peak heart rate and dyspnoea and fatigue ratings at the end of test.
Measured: baseline, 45+/-5 day and 1 year +/- 2 weeks
Quality of life questionnaires
Measured: baseline, 45+/-5 day and 1 year +/- 2 weeks
Number of steps walked daily measured by actigraphy
Actigraphy is an objective measurement of physical activity using a device that measures acceleration and movement (accelerometer). The number of steps walked daily is used to assess free daily-living activity in clinical trials. It is measured using an accelerometer worn 24 hours a day during five days. In this study, we will use the triaxial accelerometer Actigraph GT3X®. Instructions for the medical device use are provided on the website https://www.theactigraph.com.
The patient will be instructed to wear the accelerometer around the wrist 24 hours a day during 5 consecutive days including week-end and will be asked to maintain usual routine activity. The number of steps walked daily will be the average of the daily number of steps over the five days.
Measured: baseline, 45+/-5 day and 1 year +/- 2 weeks
Flow-mediated dilation
Flow-mediated dilatation (FMD) of the brachial artery will be calculated according to standard recommendations. Briefly, a pneumatic cuff will be placed on the right forearm distal to the elbow. The probe will be placed approximately midway between the antecubital and axillary regions and secured with a stereoscopic arm. Basal diameter and velocity will be recorded continuously for a minimum period of one minute. The cuff will then be inflated to 250 mm Hg for 5 minutes before sudden deflation to induce post-ischemic hyperemia. Fifteen minutes later, baseline measurements will be repeated to measure endothelial-independent, nitrate-induced dilatation. Nitrate-induced dilatation (NMD) will be calculated 4 min after sublingual administration of 0.3 mg trinitrin (NATISPRAY, Teofarma S.R.L. Italy). FMD and NMD will be expressed as a percentage change in basal diameter and in mm, after post-ischemic hyperemia and after administration of nitrate derivatives, respectively.
Measured: baseline, 45+/-5 day and 1 year +/- 2 weeks
BODE index
The BODE index is a multidimensional index of disease severity in COPD that incorporates four independent predictors: the body mass index (BMI), the degree of airflow obstruction assessed by the Forced Expiratory Volume in one second (FEV1), the modified Medical Research Council (mMRC) dyspnea scale, and the exercise capacity assessed by the 6-min walking distance (6MWD) test.
Measured: baseline, 45+/-5 day and 1 year +/- 2 weeks
COPD Assessment Test (CAT)
the COPD Assessment Test (CAT) is a patient-completed questionnaire assessing globally the impact of COPD (cough, sputum, dysnea, chest tighteness) on health status. CAT scores range from 0 to 40. Higher scores indicate a more severe impact of COPD on the patient's life. The difference between stable and exacerbating patients is five units. No target score represents the best possible outcome.
Measured: baseline, 45+/-5 day and 1 year +/- 2 weeks
Visual Simplified Respiratory Questionnaire (VSRQ)
The Visual Simplified Respiratory Questionnaire (VSRQ) is designed to assess health-related quality of life (HRQoL) in patients with chronic obstructive pulmonary disease (COPD). It contains eight items: dyspnea, anxiety, depressed mood, sleep, energy, daily activities, social activities and sexual life.
Measured: baseline, 45+/-5 day and 1 year +/- 2 weeks
mMRC dyspnea scale
the Modified Medical Research Council (mMRC) Dyspnea Scale Stratifies severity of dyspnea in respiratory diseases, particularly COPD. The higher the degree, the more severe the shortness of breath.
Measured: baseline, 45+/-5 day and 1 year +/- 2 weeks
DIsability RElated to COPD Tool (DIRECT)
The DIsability RElated to COPD Tool (DIRECT) is a 10-item questionnaire that specifically assesses COPD-related disability.
Measured: baseline, 45+/-5 day and 1 year +/- 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jan 2024
- Study start25 Jan 2024 (estimated)
- Primary completion25 Jan 2026 (estimated)
- Study completion25 Sep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Obstructive Pulmonary Disease SevereStudies of the same condition, open and under way.
- More trials run by University Hospital, GrenobleThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Grenoble
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06212765
- Sponsor's protocol ID
- tbp
- Acronym
- CITRUS
- Status last verified
- Oct 2023
- First submitted
- 12 Dec 2023
- Last updated
- 19 Jan 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 19 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Oral Citrulline Supplementation on Fat-free Mass in COPD Patients With Malnutrition
- ClinicalTrials.gov ID
- NCT06212765
- Acronym / sponsor ID
- CITRUS / tbp
- Keywords
- COPD, L-citrulline, Malnutrition
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- University Hospital, GrenobleUniversity, hospital or other
- Study start
- 25 Jan 2024 (estimated)
- Primary completion
- 25 Jan 2026 (estimated)
- Study completion
- 25 Sep 2026 (estimated)
- First posted
- 19 Jan 2024 (actual)
- 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.
Chronic obstructive pulmonary disease (COPD) is complicated by malnutrition in 20-70% of cases. In COPD, low fat-free mass is associated with a higher risk of morbidity and mortality. L-citrulline is a non-protein amino acid that has a direct effect on muscle protein synthesis. Oral supplementation with L-citrulline (10 g/day) in malnourished patients has shown to increase fat-free mass. The effects of L-citrulline supplementation in malnourished COPD patients are unknown.
The main objective of this prospective, single-centre, randomised, double-blind, placebo-controlled study will be to determine the impact of 45 days of nutritional supplementation with L-citrulline (10 g/day) on lean body mass (fat-free mass index (in kg.m-2) measured by bioelectrical impedance analysis) in malnourished patients (BMI < 20 kg/m2 if < 70 years old or < 22 kg/m2 if ≥ 70 years old) with COPD at stages 3-4 of the GOLD classification.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Citrulline | Experimental | Drug: L-citrullineThe experimental product is 100% L-citrulline. Each pod will contain 10 grams of L-citrulline. Ten grams of L-citrulline provide 2.4 g of nitrogen. |
| Standard care | Active comparator | Drug: L-citrullineThe active comparator is a mixture of the six non-essential amino acids. In order for the active comparator to be iso-nitrogenated compared with the experimental product, it will provide 2.4 g of nitrogen per pod. The active comparator will combine 13.2 % alanine, 19.8 % aspartate, 11.2 % glycine, 17.1 % proline, 15.6 % serine and 23.1 % histidine, for a total of 13 g of amino acids per pod. |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Men and women aged 50 and over
- COPD stage 3 or 4 according to GOLD criteria
- BMI < 20 kg/m2 if < 70 years old or < 22 kg/m2 if ≥ 70 years old
- Suspicion of sarcopenia marked by a score of 4 or more on the SARC-F questionnaire
- Absence of severe COPD exacerbation for at least 3 months
Key exclusion criteria (9 listed)
- Main respiratory disease other than COPD
- Daily long-term use of systemic corticosteroids (>6 months per year, whatever the dose)
- Severe and end-stage renal insufficiency (creatinine clearance <30ml/min)
- Patient with severe hypotension, uncontrolled hypertension (at investigator's discretion)
- Contraindication to L-citrulline intake: VKA and/or cancer chemotherapy
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-citrullineto take 1 pod a day for 45 days | Drug | Citrulline, Standard care |
Primary outcome
Fat Free Mass Index
Time frame: baseline, 45+/-5 day and 1 year +/- 2 weeks
Fat Free Mass Index (in kg.m-2) measured by bioelectrical impedance analysis
11 secondary outcomes
Grip strength
Time frame: baseline, 45+/-5 day and 1 year +/- 2 weeks
Maximum quadriceps strength
Time frame: baseline, 45+/-5 day and 1 year +/- 2 weeks
6-minute walk test
Time frame: baseline, 45+/-5 day and 1 year +/- 2 weeks
Quality of life questionnaires
Time frame: baseline, 45+/-5 day and 1 year +/- 2 weeks
Number of steps walked daily measured by actigraphy
Time frame: baseline, 45+/-5 day and 1 year +/- 2 weeks
Flow-mediated dilation
Time frame: baseline, 45+/-5 day and 1 year +/- 2 weeks
BODE index
Time frame: baseline, 45+/-5 day and 1 year +/- 2 weeks
COPD Assessment Test (CAT)
Time frame: baseline, 45+/-5 day and 1 year +/- 2 weeks
Visual Simplified Respiratory Questionnaire (VSRQ)
Time frame: baseline, 45+/-5 day and 1 year +/- 2 weeks
mMRC dyspnea scale
Time frame: baseline, 45+/-5 day and 1 year +/- 2 weeks
DIsability RElated to COPD Tool (DIRECT)
Time frame: baseline, 45+/-5 day and 1 year +/- 2 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jan 2024.
- Individual participant dataSharing planned: Yes
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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.
Samarmar Chacaroun, PhD contact
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing L-citrulline in people with Chronic Obstructive Pulmonary Disease Severe and Malnutrition, run by University Hospital, Grenoble.
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 5 inclusion and 9 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 19 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
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?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 Bruno Degano, MD, PhD (0033476766400, bdegano@chu-grenoble.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Fat Free Mass Index (time frame: baseline, 45+/-5 day and 1 year +/- 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 19 Jan 2024.