Clinical trial NCT03310177: Relationship Between Metabolic Profile and Clinical Phenotype in Chronic Obstructive Pulmonary Disease
Official title: Compartmental Analysis of Metabolite Profiles Associated With Disease Phenotype in Smokers With and Without Chronic Obstructive Pulmonary Disease
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Chronic Obstructive Pulmonary Disease
Keywords: Chronic Obstructive Pulmonary Disease
Metabolomics
Lead sponsor: Peking University Third Hospital
Sponsor class: OTHER
First posted: 2017-10-16
Enrollment: 167
Sex: MALE
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Clinically stable patients with COPD and controls without COPD are enrolled.

Brief summary: Despite the high prevalence of chronic obstructive pulmonary disease (COPD), there continues to be a large gap in our understanding of disease pathogenesis and mechanisms accounting for large variability in disease phenotype. Untargeted metabolomics is an ideal approach to uncover the metabolic basis of disease, as well as discover unique drug target opportunities aimed at these nodal metabolic drivers of disease. There are very limited data from metabolomics studies from plasma/serum and exhaled breath condensate that suggest certain metabolic pathways or metabolites might predict the presence and/or severity of COPD phenotypes.

Here, the investigators hope to generate comprehensive, compartment specific (blood and lung) metabolite profiles that will be correlated with various clinical phenotypes of COPD, using a complementary approach of untargeted nuclear magnetic resonance (NMR) and liquid chromatography (LC)- mass spectroscopy (MS) -based metabolomics.

Detailed description: Despite the high prevalence of chronic obstructive pulmonary disease (COPD), there continues to be a large gap in our understanding of disease pathogenesis and mechanisms accounting for large variability in disease phenotype. Untargeted metabolomics is an ideal approach to uncover the metabolic basis of disease, as well as discover unique drug target opportunities aimed at these nodal metabolic drivers of disease. There are very limited data from metabolomics studies from plasma/serum and exhaled breath condensate that suggest certain metabolic pathways or metabolites might predict the presence and/or severity of COPD phenotypes.

The investigators hypothesize that: 1) smokers with COPD will have a metabolomics signature that is distinct from healthy non-COPD smokers; 2) this signature will be associated with clinically relevant manifestations of disease (e.g., GOLD classification, PFT).

The availability of biosamples from a well-characterized population of smokers with and without COPD, combined with our established in-house metabolomics expertise, will robustly allow to test these novel hypotheses. The investigators hope to generate comprehensive, compartment specific (blood and lung) metabolite profiles that will be correlated with various clinical phenotypes of COPD, using a complementary approach of untargeted nuclear magnetic resonance (NMR) and liquid chromatography (LC)- mass spectroscopy (MS) -based metabolomics. Moreover, this strategy may identify previously unrecognized metabolic pathways that are dysregulated in COPD. Collectively, these data will be used to direct a prospective clinical study to determine the association between metabolomics signatures and clinical outcomes.

Eligibility criteria: IInclusion Criteria:

1. males aged 40-80;
2. diagnosed with COPD according to the GOLD guidelines;
3. clinically stable patients without medication changes or exacerbation in two months;
4. smoking history of more than 10 pack years

Exclusion Criteria:

1. diagnosed with unstable cardiovascular diseases, significant renal or hepatic dysfunction or mental incompetence;
2. diagnosed with asthma, active pulmonary tuberculosis, diffuse panbronchiolitis, cystic fibrosis, clinically significant bronchiectasis, exacerbation of COPD or pneumonia in two months;
3. prescribed immunosuppressive medications.

Primary outcomes:
measure: Metabolites that can predict the progress of lung function
timeFrame: 3 months
Secondary outcomes:
measure: Metabolites that can predict the severity of emphysema
timeFrame: 3 months
measure: Metabolites that are associated with inflammatory mediators
timeFrame: 3 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University Third Hospital
state: Beijing
Study officials:
References:
citation: Diao W, Labaki WW, Han MK, Yeomans L, Sun Y, Smiley Z, Kim JH, McHugh C, Xiang P, Shen N, Sun X, Guo C, Lu M, Standiford TJ, He B, Stringer KA. Disruption of histidine and energy homeostasis in chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis. 2019 Sep 3;14:2015-2025. doi: 10.2147/COPD.S210598. eCollection 2019.