Intermittent Hypoxemia, Lung Function Decline, Morbidity, and Mortality in COPD (PROSA Study).

Chronic Obstructive Pulmonary Disease (COPD) Clinical Trial

— PROSA  

Official title:

Prospective Observational Study to Assess the Influence of Intermittent Hypoxaemia on Lung Function Decline, Morbidity, and Mortality in COPD Patients (PROSA Study)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06265623
• Other study ID #: UKE-IKPT 2024/01
• Status: Not yet recruiting
• Start date: March 1, 2024
• Est. completion date: September 30, 2029

Study information

• Verified date: February 2024
• Source: Universitätsklinikum Hamburg-Eppendorf
• Contact: Rainer Böger, Prof. Dr.
• Phone: +49-40-7410
• Email: boeger[@]uke.de
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study aims to analyze if patients with chronic obstructive lung disease who experience a decline of blood oxygen saturation during physical exercise have a disease course different from that of COPD patients who do not experience a decline in blood oxygen saturation during exercise. Patients will be followed for a total of 3 years.

Description:

The major aim of the study is to test whether intermittent hypoxaemia is a major driver of the progression of chronic obstructive lung disease (COPD). The second aim is to analyse whether dysregulation of the L-arginine / dimethylarginine pathway is a mechanistic link between intermittent hypoxemia and lung function decline, and whether plasma biomarkers are suitable to identify COPD patients at high risk of rapid lung function decline and mortality.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 148
• Est. completion date: September 30, 2029
• Est. primary completion date: September 30, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Patients of both sexes with a diagnosis of chronic obstructive lung disease (COPD) stages 2-3, groups B and E according to GOLD 38 as assessed by their primary family doctor or pneumology specialist who are treated with long-acting bronchodilators on a stable dose for at least four months prior to inclusion into the study;

2. Age at inclusion 18 - 80 years;

3. Physical ability and willingness to perform 6-minute walk testing and bicycle ergometry testing;

4. Signed written informed consent form

Exclusion Criteria:

1. Participation in another clinical study within the last 3 months before inclusion into the present study;

2. Any somatic or psychic disease that may hamper participation in the study or compliance with the study protocol (at the investigator's discretion);

3. Any somatic disease that puts the patient at increased risk when performing the exercise tests or impairs the patient's ability to properly perform the exercise tests, like advanced coronary artery disease, advanced chronic heart failure, uncontrolled hypertension, orthopaedic, or neurological diseases (non-exclusive list of examples);

4. Any disease or health condition that reduces the patient's life expectancy to less than the expected time frame of this study, other than chronic obstructive lung disease (at the investigator's discretion);

5. Pregnancy or nursing.

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease (COPD)
• Hypoxia
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Other:
• No active intervention, but observational follow-up
Patients remain in usual care by their pulmonary medicine specialists and are being observed during annual follow-up investigations during up to 3 years

Locations

Country	Name	City	State
Germany	University Medical Center Hamburg-Eppendorf, Institute of Clinical Pharmacology and Toxicology	Hamburg

Sponsors (1)

Lead Sponsor	Collaborator
Universitätsklinikum Hamburg-Eppendorf

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Difference in FEV1(% of LLN) between baseline and end-of-follow-up	The difference in measured FEV1 assessed by spirometry and expressed as percent of the lower limit of the normal distribution based upon the Global Lung Function 2022 Equations, by comparing results of the baseline measurement with those of the last investigation during up to three years of follow-up	3 years
Secondary	Difference in all-cause mortality during follow-up between groups	Number of patients who died from any cause during follow-up in either of the two groups.	3 years
Secondary	Difference in COPD-related mortality during follow-up between groups	Number of patients who died from COPD and its complications during follow-up in either of the two groups.	3 years
Secondary	Difference in frequency of hospital admissions for exacerbation of COPD during follow-up between groups	Number of patients who were admitted to hospital because of exacerbated COPD during follow-up in either of the two groups.	3 years
Secondary	Difference in frequency of hospital admissions for causes other than exacerbation of COPD during follow-up between groups	Number of patients who were admitted to hospital for any other reason than exacerbated COPD during follow-up in either of the two groups.	3 years
Secondary	Sensitivity of plasma biomarkers (spec. ADMA and SDMA) to predict the prevalence of exertional desaturation in COPD patients	Sensitivity analysis (ROC analysis) of biomarkers and presence of exertional desaturation (as defined in the protocol) or not in study participants.	3 years
Secondary	Sensitivity and specificity of plasma biomarkers (spec. ADMA and SDMA) measured at baseline to prospectively predict the slope of lung function decline in COPD patients	Prospective survival analysis (Kaplan-Meier) of plasma biomarkers measured at the time of study inclusion and the difference in FEV1(% of lower limit of normal) between baseline and last measurement during follow-up.	3 years
Secondary	Sensitivity and specificity of plasma biomarkers at baseline to prospectively predict the mortality rate in COPD patients	Prospective survival analysis (Kaplan-Meier) of plasma biomarkers measured at the time of study inclusion and total mortality during follow-up.	3 years
Secondary	Difference in incidence and extent of exercise hypoxemia between carriers and non-carriers of single nucleotide polymorphisms (SNPs) in genes of the L-arginine - dimethylarginine pathway	Comparison of the rates of prevalence of exertional desaturation between homozygous carriers of the major versus minor allele of SNPs in the NOS III, DDAH1, DDAH2, PRMT1-9, AGXT2, and ARG1-2 genes.	3 years
Secondary	Difference in positive and negative predictive value of bicycle ergometry, 6-minute walk test, and 15-sec breath-hold test to discriminate between COPD patients with exertional desaturation versus those without exertional desaturation	Comparison of sensitivity and specificity analyses (ROC analyses) of the outcome of named exercise tests to detect exertional desaturation in study participants.	3 years