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

Overview

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.

Interventions

• Dietary supplement Targeted nutrient supplementation (Long-drink)
  Once daily for at least 12 months
• Dietary supplement Placebo supplement
  Once daily for at least 12 months
• Behavioral Counselling
  Counselling on healthy lifestyle (in particular physical activity, smoking cessation) and weight management by motivational interviewing

Primary outcome measures

• Change in physical activity level assessed by measuring step count with accelerometry [Time frame: 0, 3, and 12-14 months and in case of hospitalization for COPD exacerbation within one week after discharge and 4 weeks later]
• Change in generic health status measured by EuroQol-5 dimensions (EQ-5D) [Time frame: 0, 3, and 12-14 months and in case of hospitalization for COPD exacerbation within one week after discharge and 4 weeks later]

Secondary outcome measures (12)

• Change in cognitive function measured by the Neuropsychological test automated battery (CANTAB) [Time frame: 0-12 months; and in case of hospitalization for COPD exacerbation within one week after discharge and 4 weeks later.]
• Change in Depression Anxiety Stress Scale 21 (DASS-21) [Time frame: 0-12 months; and in case of hospitalization for COPD exacerbation within one week after discharge and 4 weeks later.]
• Change in Hospital and Anxiety Scale (HADS) [Time frame: 0-12 months; and in case of hospitalization for COPD exacerbation within one week after discharge and 4 weeks later.]
• Change in Cohen's Perceived Stress Scale (PSS) [Time frame: 0-12 months; and in case of hospitalization for COPD exacerbation within one week after discharge and 4 weeks later.]
• Change in blood pressure after the socially evaluated cold pressure test [Time frame: 0-12 months.]
• Change in cortisol in the saliva after the socially evaluated cold pressure test [Time frame: 0-12 months.]
• Change in hair cortisol [Time frame: 0 and 12-14 months and in case of hospitalization for COPD exacerbation within one week after discharge and 4 weeks later.]
• Change in lower extremity performance by the short physical performance battery (SPPB) [Time frame: 0-12 months; and in case of hospitalization for COPD exacerbation within one week after discharge and 4 weeks later.]
• Change in muscle strength by measuring handgrip strength [Time frame: 0-12 months; and in case of hospitalization for COPD exacerbation within one week after discharge and 4 weeks later.]
• Change in respiratory muscle strength by measuring the inspiratory and expiratory mouth pressure [Time frame: 0-12 months; and in case of hospitalization for COPD exacerbation within one week after discharge and 4 weeks later.]
• Change in exercise performance by measuring the 6 minute walking distance [Time frame: 0-12 months.]
• Change in body composition by performing Dual energy X-ray absorptiometry (DEXA-scan) [Time frame: 0-12 months.]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

Netherlands · 1 center

• Maastricht University Medical Centre+ (MUMC+) — Maastricht

Publications

• Born CDC, Beijers RJHCG, van Iersel LEJ, Muijrers IHMJE, Schuurman LT, Gerards SMPL, Simons SO, Gosker HR, van Helvoort A, Schols AMWJ, Crutzen R. Assessing Lifestyle Goal Setting in Patients with COPD. Int J Chron Obstruct Pulmon Dis. 2026 Mar 31;21:579191. doi: 10.2147/COPD.S579191. eCollection 2026. PMID 41939921
• van Iersel LEJ, Beijers RJHCG, Simons SO, Schuurman LT, Shetty SA, Roeselers G, van Helvoort A, Schols AMWJ, Gosker HR. Characterizing gut microbial dysbiosis and exploring the effect of prebiotic fiber supplementation in patients with COPD. Eur J Nutr. 2025 Jun 7;64(5):210. doi: 10.1007/s00394-025-03733-7. PMID 40481968
• 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. PMID 35296491

Identifiers

NCT: NCT03807310 · METC18-011 · 10.2.16.119

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗