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Trial registered on ANZCTR


Registration number
ACTRN12619001479190
Ethics application status
Approved
Date submitted
30/07/2019
Date registered
25/10/2019
Date last updated
25/10/2019
Date data sharing statement initially provided
25/10/2019
Date results information initially provided
25/10/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Serum lipidomics in patients with sarcoidosis before and after pulmonary rehabilitation
Scientific title
Serum lipidomics in patients with sarcoidosis before and after pulmonary rehabilitation
Secondary ID [1] 298690 0
Grant KNW-1-093/K/6/0 from the Medical University of Silesia, Poland
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
sarcoidosis 313586 0
Condition category
Condition code
Respiratory 312486 312486 0 0
Other respiratory disorders / diseases
Physical Medicine / Rehabilitation 312487 312487 0 0
Other physical medicine / rehabilitation

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study aimed to determine the use of lipid profiling to assess the effects of pulmonary rehabilitation on patients with sarcoidosis.

Serum was collected from 14 patients with newly diagnosed II stage of sarcoidosis (up to 6 months, aged 34–63 years) before and after pulmonary rehabilitation in the Department of Lung Diseases and Tuberculosis between November 2015 and December 2017.

Before and after pulmonary rehabilitation all patients had evaluated:
- fatigue by Fatigue Assessment Scale (FAS)
- the level of dyspnea by The Medical Research Council (MRC) questionnaire
- forced vital capacity, forced expiratory volume during the first second, total lung capacity, and transfer factor for carbon monoxide (TLCO)
- mobility by the 6-minute walk test (6MWT)
- muscle strength: the maximal isometric grip strengths of the left and right hands by hydraulic hand dynamometer and expressed in kilograms (kg), respiratory muscle force by the maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP).
- blood analysis: serum glucose, urea, creatinine, total protein, C-reactive protein (CRP), angiotensin converting enzyme (ACE), total protein, total cholesterol (TCH), triglycerides (TG), low-density lipoprotein concentration (LDL-c), and high-density lipoprotein concentration (HDL-c), the markers of inflammation and cell damage (sICAM-1, TNF-a, and IL-6), myosin and myoglobin.

Intervention
Patients were encouraged to start a 3-week physical training program (5 days a week), which was supervised by a physical therapist and based on their physical performance assessed at baseline. The exercise program included three major components, namely, aerobic endurance training (stationary cycling or treadmill up to 30 min/day), inspiratory muscle training, and peripheral muscle strength training (three sets of 15–20 repetitions of five different exercises). The resistance level was individualized for each patient (in accordance with patient preference), reassessed, and adjusted after every session using the Borg Rating of Perceived Exertion. Inspiratory muscle training was introduced using the Threshold IMP (Healthdyne Technologies, Great Britain) and consisted of six courses of inspiratory exercises with five inspiratory maneuvers in each series and 1 min of rest between them. After completing the exercises, the subjects were required to cool down for 5 min. All exercise modalities were progressed regularly by an experienced exercise physiologist to maintain dyspnea Borg RPE score of 13-15. Pulse-oximetry was used to monitor peripheral oxygen saturation levels during exercises. Supplemental oxygen use during training was commensurate with current prescriptions. It was provided during training if SpO2 on room air was below 88% whilst exercising and was titrated to maintain a SpO2 above 90%. During exercises pulse was monitored continuously, and patients were encouraged to increase their effort to 70% of Pulse max according to the Karvelen’s formula.
Intervention code [1] 314959 0
Rehabilitation
Intervention code [2] 315350 0
Treatment: Other
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 320662 0
Changes in serum total cholesterol.
Timepoint [1] 320662 0
Baseline, 3 weeks (post pulmonary rehabilitation)
Primary outcome [2] 320663 0
Changes in serum cholesterol esters.
Timepoint [2] 320663 0
Baseline, 3 weeks (post pulmonary rehabilitation)
Primary outcome [3] 321786 0
Changes in serum free cholesterol.
Timepoint [3] 321786 0
Baseline, 3 weeks (post pulmonary rehabilitation)
Secondary outcome [1] 372424 0
Changes in serum triglycerides.
Timepoint [1] 372424 0
Baseline, 3 weeks (post pulmonary rehabilitation)
Secondary outcome [2] 372425 0
Changes in serum low-density lipoprotein concentration.
Timepoint [2] 372425 0
Baseline, 3 weeks (post pulmonary rehabilitation)
Secondary outcome [3] 372426 0
Changes in serum high-density lipoprotein concentration.
Timepoint [3] 372426 0
Baseline, 3 weeks (post pulmonary rehabilitation)
Secondary outcome [4] 372427 0
Changes in serum sphingomyelin.
Timepoint [4] 372427 0
Baseline, 3 weeks (post pulmonary rehabilitation)
Secondary outcome [5] 376200 0
Changes in serum fatty acid.
Timepoint [5] 376200 0
Baseline, 3 weeks (post pulmonary rehabilitation)
Secondary outcome [6] 376201 0
Changes in serum phosphatidylcholin.
Timepoint [6] 376201 0
Baseline, 3 weeks (post pulmonary rehabilitation)
Secondary outcome [7] 376202 0
Changes in serum palmitic acid.
Timepoint [7] 376202 0
Baseline, 3 weeks (post pulmonary rehabilitation)
Secondary outcome [8] 376203 0
Changes in the distance walked in a 6MWT.
Timepoint [8] 376203 0
Baseline, 3 weeks (post pulmonary rehabilitation)
Secondary outcome [9] 376204 0
Changes in fatigue perceived assessed using the Fatigue Assessment Scale.
Timepoint [9] 376204 0
Baseline, 3 weeks (post pulmonary rehabilitation)
Secondary outcome [10] 376205 0
Changes in level of dyspnea perceived assessed using the Modified Medical Research Council questionnaire.
Timepoint [10] 376205 0
Baseline, 3 weeks (post pulmonary rehabilitation)
Secondary outcome [11] 376206 0
Changes in grip strength measured with a Meden-Inmed Baseline hydraulic hand dynamometer.
Timepoint [11] 376206 0
Baseline, 3 weeks (post pulmonary rehabilitation)
Secondary outcome [12] 376207 0
Changes in respiratory muscles strength: MIP - maximal inspiratory pressure, determined with MicroRPM equipment (Oxford inc.).
Timepoint [12] 376207 0
Baseline, 3 weeks (post pulmonary rehabilitation)
Secondary outcome [13] 376208 0
Changes in respiratory muscles strength: MEP - maximal expiratory pressure, determined with MicroRPM equipment (Oxford inc.).
Timepoint [13] 376208 0
Baseline, 3 weeks (post pulmonary rehabilitation)

Eligibility
Key inclusion criteria
Serum was collected from 14 patients with newly diagnosed II stage of sarcoidosis (up to 6 months, aged 34–63 years) before and after pulmonary rehabilitation in the Department of Lung Diseases and Tuberculosis between November 2015 and December 2017.
The patients were diagnosed based on consistent clinical features, bronchoalveolar lavage (BAL) fluid analysis, and/or biopsy-proven non-caseating epithelioid cell granulomas.
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- ischemic heart disease, congestive heart failure, severe pulmonary hypertension
- substantial liver function impairments, diabetes
- stroke in medical history
- addictions: tobacco, drugs, alcohol
- increased cognitive impairments in the form of dementia
- neurological impairments or impairments of the locomotor system precluding the performance of the exercises
- lack of consent and will to cooperate

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Routine biochemical compounds were analyzed using matched-pairs t-test or Wilcoxon matched-pairs signed-rank test (univariate) and orthogonal partial least squares-DA (OPLS-DA) and OPLS-effect projection (EP; multivariate tests). Mean centering, log transformation, and Pareto scaling were applied before the discriminant analysis (OPLS-DA).

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 21677 0
Poland
State/province [1] 21677 0
Silesia

Funding & Sponsors
Funding source category [1] 303242 0
University
Name [1] 303242 0
Medical University of Silesia
Address [1] 303242 0
15 Poniatowskiego Street
40-055 Katowice
Country [1] 303242 0
Poland
Primary sponsor type
University
Name
Medical University of Silesia
Address
15 Poniatowskiego Street
40-055 Katowice
Country
Poland
Secondary sponsor category [1] 303251 0
None
Name [1] 303251 0
Address [1] 303251 0
Country [1] 303251 0
Other collaborator category [1] 280849 0
Government body
Name [1] 280849 0
Nalecz Institute of Biocybernetics and Biomedical Engineering, Polish Academy of Sciences
Address [1] 280849 0
4 Trojdena Street
02-109 Warszawa
Country [1] 280849 0
Poland

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303786 0
The Research Ethics Committee of the Medical University of Silesia
Ethics committee address [1] 303786 0
15 Poniatowskiego Street
40-055 Katowice
Ethics committee country [1] 303786 0
Poland
Date submitted for ethics approval [1] 303786 0
Approval date [1] 303786 0
17/11/2015
Ethics approval number [1] 303786 0
KNW/0022/KB1/123/15

Summary
Brief summary
This study aimed to determine the use of lipid profiling to assess the effects of pulmonary rehabilitation on patients with sarcoidosis. Serum was collected from 14 patients with stage II sarcoidosis before and after pulmonary rehabilitation. Proton nuclear magnetic resonance (NMR) spectroscopy combined with orthogonal partial least squares-discriminant analysis (DA) was used. Twenty-five NMR signals from lipid compounds were selected for further analysis. The DA correctly classified the patients into groups in 96% of the cases before and after rehabilitation. Analysis of response to the rehabilitation indicated that fatty acids, plasminogen, and total cholesterol were the most involved. Multivariate DA yielded a list of potential biomarkers that were significantly higher in the patients after rehabilitation. This study presents a novel method that can be used to analyze the responses to pulmonary rehabilitation in patients with sarcoidosis.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 94802 0
Prof Dariusz Jastrzebski
Address 94802 0
Department of Lung Diseases and Tuberculosis, School of Medicine with the Division of Dentistry, Medical University of Silesia
1 Koziolka Street
41-800 Zabrze
Country 94802 0
Poland
Phone 94802 0
+48323732235
Fax 94802 0
Email 94802 0
djastrzebski@sum.edu.pl
Contact person for public queries
Name 94803 0
Mrs Sabina Kostorz-Nosal
Address 94803 0
Department of Lung Diseases and Tuberculosis, School of Medicine with the Division of Dentistry, Medical University of Silesia
1 Koziolka Street
41-800 Zabrze
Country 94803 0
Poland
Phone 94803 0
+48323732235
Fax 94803 0
Email 94803 0
sabina_kostorz@o2.pl
Contact person for scientific queries
Name 94804 0
Mrs Sabina Kostorz-Nosal
Address 94804 0
Department of Lung Diseases and Tuberculosis, School of Medicine with the Division of Dentistry, Medical University of Silesia
1 Koziolka Street
41-800 Zabrze
Country 94804 0
Poland
Phone 94804 0
+48323732235
Fax 94804 0
Email 94804 0
sabina_kostorz@o2.pl

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
There is no plan to share individual patient data publicly
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – plain English summary
Changes in 6-minute walking test were the only parameters that showed significant differences between the responders and non-responders. Significantly high correlations were noted between the responders to rehabilitation and Modified Medical Research Council questionnaire results, 6-minute walking test and high-density lipoprotein concentration. Analysis of routine biochemical compounds (C-reactive protein, high-density lipoprotein, low-density lipoprotein, tumor necrosis factor alpha, interleukin 6, myosin, myoglobin, triglycerides, total cholesterol and intercellular adhesion molecule 1) showed differences between the patients before and after rehabilitation. The most important parameters that influenced the differentiation of the groups were myosin and interleukin 6 (after rehabilitation myosin levels increased, interleukin-6 levels decreased) whereas in the lipid profile analysis: triglycerides, phosphatidylcholine/sphingomyelin, fatty acid, total cholesterol, free cholesterol, phosphatidylcholine, cholesterol esters and unassigned signal. Among the routinely measured biochemical compounds, intercellular adhesion molecule 1 and myoglobin were the most altered after rehabilitation due to changes in their higher absolute values.