Clinical trial NCT03807310: Targeted Nutrient Supplement in COPD (NUTRECOVER-trial)
Official title: The Effect of Targeted Nutrient Supplementation on Physical Activity and Healthy Related Quality of Life in COPD
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Pulmonary Disease, Chronic Obstructive
Keywords: COPD
nutrient supplementation
Physical activity
Health related quality of life
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
Collaborators: name: Nutricia Research
First posted: 2019-01-16
Enrollment: 166
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Next to the 166 COPD patients that receive the nutritional supplement, a subgroup of 30 healthy controls will be included for baseline comparison of the microbiome composition. These healthy controls will not be included in the intervention arm.
Primary purpose: TREATMENT

Brief summary: The overall objective is to investigate the efficacy of targeted nutrient supplementation on daily physical activity level as well as generic health status in patients with COPD. Additionally the investigators aim to investigate the relative effect of targeted nutrient supplementation on the recovery after hospitalization for a COPD exacerbation. The secondary objective is to investigate the effect of targeted nutrient supplementation on mental health, physical performance, blood markers, patient related outcomes and gut health. Additionally, a secondary objective is to compare the gut microbiome composition of patients with COPD compared to healthy controls.

Detailed description: Rationale: Impaired physical and mental health are common features in COPD adversely affecting disease course and quality of life. Furthermore, nutritional status is often impaired due to dietary and plasma nutrient deficiencies, decreased muscle oxidative metabolism and impaired intestinal permeability. The investigators hypothesize that targeted nutrient supplementation can lead to gut-muscle-brain axis-mediated amelioration of physical, cognitive and mental health domains, resulting in a healthier lifestyle, in patients with COPD.

Study design: Randomized, placebo-controlled, double-blind trial.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The nutrient supplement is hypothesized to have beneficial effects on general health because it applies physical and mental health domains. The healthy lifestyle counselling aims to improve medical adherence, to address a healthier lifestyle and to manage weight loss which would contribute to improved general health. Risks and inconveniences are limited to the time investment associated with taking the supplements and measuring days. During the test-days various non-invasive measurements as well as minor invasive blood sampling will be performed. The investigators expect no risk of the nutrient supplementation. Healthy controls will only attend a subgroup of baseline measurements which are limited to non-invasive measurements and one minor invasive blood sampling. Healthy controls will not receive the nutritional supplement.

Eligibility criteria: Inclusion Criteria COPD Patients:

* COPD patients with moderate to very severe disease stage according to GOLD criteria (i.e. GOLD stage II-IV);
* Medically stable.

Exclusion Criteria COPD Patients:

* Age \<18 years;
* Allergy or intolerance to components of the study product;
* Not willing or not able to quit vitamin D or fatty acid supplement intake;
* Investigator's uncertainty about the willingness or ability of the patient to comply with the protocol requirements (e.g. leg amputation) or patients suffering from other acute or unstable chronic diseases that will compromise the study outcome (e.g. active cancer requiring treatment);
* Participation in any other study involving investigational or marketed products concomitantly or within four weeks prior to entry into the study;
* Patients with terminal illness;
* Recent hospital admission (\<4 weeks prior to the start of the study);
* Temporary oral steroid or antibiotics use due to a COPD exacerbation in the last 4 weeks;
* Lung malignancy in the previous 5 years;
* Diagnosis of dementia or neurodegenerative disease (e.g., Alzheimer's disease, Parkinson's disease, Huntington's chorea, frontotemporal dementia) in the medical records;
* Recent diagnosis of cerebral conditions (\<1 year e.g. cerebral infarction, hemorrhage, brain tumors, transient ischemic attack) in the medical records;
* Any medical condition that significantly interferes with digestion and/or gastrointestinal function (e.g. short bowel syndrome, inflammatory bowel disease, gastric ulcers, gastritis, (gastro)-enteritis, GI-cancer) as judged by the investigator.

Inclusion Criteria Healthy Controls

* Forced expiratory volume in 1 second/Forced vital capacity \> 0.7;
* Medically stable.

Exclusion Criteria Healthy Controls

* Age \<18 years;
* Investigator's uncertainty about the willingness or ability of the patient to comply with the protocol requirements (e.g. leg amputation) or patients suffering from other acute or unstable chronic diseases that will compromise the study outcome (e.g. active cancer requiring treatment);
* Participation in any other study involving investigational or marketed products concomitantly or within four weeks prior to entry into the study;
* Patients with terminal illness;
* Recent hospital admission (\<4 weeks prior to the start of the study);
* Temporary antibiotics use in the last 4 weeks;
* Lung malignancy in the previous 5 years;
* Diagnosis of dementia or neurodegenerative disease (e.g., Alzheimer's disease, Parkinson's disease, Huntington's chorea, frontotemporal dementia) in the medical records;
* Recent diagnosis of cerebral conditions (\<1 year e.g. cerebral infarction, hemorrhage, brain tumors, transient ischemic attack) in the medical records;
* Any medical condition that significantly interferes with digestion and/or gastrointestinal function (e.g. short bowel syndrome, inflammatory bowel disease, gastric ulcers, gastritis, (gastro)-enteritis, GI-cancer) as judged by the investigator.
* Diagnosis of any chronic lung disease.

Primary outcomes:
measure: Change in physical activity level assessed by measuring step count with accelerometry
timeFrame: 0, 3, and 12-14 months and in case of hospitalization for COPD exacerbation within one week after discharge and 4 weeks later
measure: Change in generic health status measured by EuroQol-5 dimensions (EQ-5D)
timeFrame: 0, 3, and 12-14 months and in case of hospitalization for COPD exacerbation within one week after discharge and 4 weeks later
Secondary outcomes:
measure: Change in cognitive function measured by the Neuropsychological test automated battery (CANTAB)
timeFrame: 0-12 months; and in case of hospitalization for COPD exacerbation within one week after discharge and 4 weeks later.
measure: Change in Depression Anxiety Stress Scale 21 (DASS-21)
timeFrame: 0-12 months; and in case of hospitalization for COPD exacerbation within one week after discharge and 4 weeks later.
measure: Change in Hospital and Anxiety Scale (HADS)
timeFrame: 0-12 months; and in case of hospitalization for COPD exacerbation within one week after discharge and 4 weeks later.
measure: Change in Cohen's Perceived Stress Scale (PSS)
timeFrame: 0-12 months; and in case of hospitalization for COPD exacerbation within one week after discharge and 4 weeks later.
measure: Change in blood pressure after the socially evaluated cold pressure test
timeFrame: 0-12 months.
measure: Change in cortisol in the saliva after the socially evaluated cold pressure test
timeFrame: 0-12 months.
measure: Change in hair cortisol
timeFrame: 0 and 12-14 months and in case of hospitalization for COPD exacerbation within one week after discharge and 4 weeks later.
measure: Change in lower extremity performance by the short physical performance battery (SPPB)
timeFrame: 0-12 months; and in case of hospitalization for COPD exacerbation within one week after discharge and 4 weeks later.
measure: Change in muscle strength by measuring handgrip strength
timeFrame: 0-12 months; and in case of hospitalization for COPD exacerbation within one week after discharge and 4 weeks later.
measure: Change in respiratory muscle strength by measuring the inspiratory and expiratory mouth pressure
timeFrame: 0-12 months; and in case of hospitalization for COPD exacerbation within one week after discharge and 4 weeks later.
measure: Change in exercise performance by measuring the 6 minute walking distance
timeFrame: 0-12 months.
measure: Change in body composition by performing Dual energy X-ray absorptiometry (DEXA-scan)
timeFrame: 0-12 months.
measure: Change in weight
timeFrame: 0-12 months; and in case of hospitalization for COPD exacerbation within one week after discharge and 4 weeks later.
measure: Change in height
timeFrame: 0-12 months
measure: Change in blood markers of systemic inflammation
timeFrame: 0-12 months; and in case of hospitalization for COPD exacerbation within one week after discharge and 4 weeks later.
measure: Change in blood markers of nutritional status
timeFrame: 0-3 months; 0-12 months; and in case of hospitalization for COPD exacerbation within one week after discharge and 4 weeks later.
measure: Change in blood markers of gut-muscle-brain cross-talk
timeFrame: 0-12 months; and in case of hospitalization for COPD exacerbation within one week after discharge and 4 weeks later.
measure: Change in fatigue by using the checklist individual strength (CIS)
timeFrame: 0-12 months; and in case of hospitalization for COPD exacerbation within one week after discharge and 4 weeks later.
measure: Change in pain using the Visual Analogue Scale (VAS)
timeFrame: 0-12 months; and in case of hospitalization for COPD exacerbation within one week after discharge and 4 weeks later.
measure: Change in sleep quality by the Pittsburgh Sleep Quality Index (PSQI)
timeFrame: 0-12 months; and in case of hospitalization for COPD exacerbation within one week after discharge and 4 weeks later.
measure: Change in intestinal fatty acid binding protein (blood) in rest
timeFrame: 0-12 months; and in case of hospitalization for COPD exacerbation within one week after discharge and 4 weeks later.
measure: Change in intestinal fatty acid binding protein (blood) after the 6MWT
timeFrame: 0-12 months.
measure: Change in gut microbiome composition (optional)
timeFrame: 0, 3 and 12 months.
Other outcomes:
measure: Change in forced expiratory volume in 1 second
timeFrame: 0-12 months; and in case of hospitalization for COPD exacerbation within one week after discharge and 4 weeks later.
measure: Change in forced vital capacity
timeFrame: 0-12 months; and in case of hospitalization for COPD exacerbation within one week after discharge and 4 weeks later.
measure: Total lung capacity
timeFrame: 0-12 months; and in case of hospitalization for COPD exacerbation within one week after discharge and 4 weeks later.
measure: Functional residual capacity
timeFrame: 0-12 months; and in case of hospitalization for COPD exacerbation within one week after discharge and 4 weeks later.
measure: Change in diffusion capacity
timeFrame: 0-12 months; and in case of hospitalization for COPD exacerbation within one week after discharge and 4 weeks later.
measure: Change in the global impacts of COPD on health status using the COPD assessment test (CAT)
timeFrame: 0-12 months; and in case of hospitalization for COPD exacerbation within one week after discharge and 4 weeks later.
measure: Change in health status using the Clinical COPD questionnaire (CCQ)
timeFrame: 0-12 months; and in case of hospitalization for COPD exacerbation within one week after discharge and 4 weeks later.
measure: Change in breathlessness using the medical research council (MRC-scale)
timeFrame: 0-12 months; and in case of hospitalization for COPD exacerbation within one week after discharge and 4 weeks later.
measure: Change in medication use by self-report
timeFrame: 0-12 months; and in case of hospitalization for COPD exacerbation within one week after discharge and 4 weeks later.
measure: Change in medical history will be assessed from medical records
timeFrame: 0-12 months; and in case of hospitalization for COPD exacerbation within one week after discharge and 4 weeks later.
measure: Change in food intake
timeFrame: 0, 3 and 12-14 months
measure: Blood gases
timeFrame: in case of hospitalization for COPD exacerbation within one week after discharge
measure: Type of infection
timeFrame: in case of hospitalization for COPD exacerbation within one week after discharge
measure: Number of patients died
timeFrame: from beginning of the study till 1 year after study completion
measure: Number of patients readmitted for a COPD exacerbation
timeFrame: from beginning of the study till 1 year after study completion
measure: Difference in gut microbiome composition between healthy controls and COPD patients
timeFrame: Baseline asssment
measure: Difference in lung function between healthy controls and COPD patients
timeFrame: Baseline asssment
measure: Difference in blood systemic inflammation between healthy controls and COPD patients
timeFrame: Baseline asssment
measure: Difference in food intake between healthy controls and COPD patients
timeFrame: Baseline asssment
measure: Difference in medication use between healthy controls and COPD patients
timeFrame: Baseline asssment
Locations:
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Centre+ (MUMC+)
state: Limburg
Study officials:
affiliation: Maastricht UMC+ / NUTRIM, Department of Respiratory Medicine
name: Annemie Schols, Prof. dr.
role: STUDY_DIRECTOR
References:
citation: Beijers RJ, van Iersel LEJ, Schuurman LT, Hageman RJJ, Simons SO, van Helvoort A, Gosker HR, Schols AM. Effect of targeted nutrient supplementation on physical activity and health-related quality of life in COPD: study protocol for the randomised controlled NUTRECOVER trial. BMJ Open. 2022 Mar 16;12(3):e059252. doi: 10.1136/bmjopen-2021-059252.