E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with chronic obstructive pulmonary disease (COPD) and concomitant vitamin D deficiency |
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E.1.1.1 | Medical condition in easily understood language |
Patients with chronic obstructive pulmonary disease (COPD) and concomitant vitamin D deficiency |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Primary objective is to assess whether vitamin D3 supplementation, in addition to physical training, improves the strength of the respiratory muscles measured as increase of MIP. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives are to assess whether vitamin D3 supplementation, in addition to physical training, improves the strength of the respiratory muscles assessed by MEP and SNIP, muscle strength of dominant leg and arm, maximal oxygenation capacity (VO2max) and endurance measured with ISWT and ESWT, lung volumes at rest (FEV1 och FVC) after bronchodilation, physical functionality including balance, muscle metabolism in the quadriceps muscle of the dominant leg before, during and after standardized exercise applying 31P-MRS, quantification of muscle mass and fat in the dominant leg using MR, QoL, COPD symptoms, fatigue, physical activity, anxiety and depression, iBODE index (a product of BMI, FEV1 % of predicted, mMRC and ISWT), biological variables for systemic inflammation, oxidative stress and muscle- and bone pathology and serum-25(OH). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Written informed consent to participate in the study
• Smoker or former smoker, ≥ 10 package-yrs
• Age ≥ 55 yrs
• COPD (defined as post-bronchodilator FEV1/FVC < 0.7)
• No reversibility defined as < 12 % increase of FEV1 and FVC and < 200 ml increase of FEV1 after bronchodilation
• FEV1 < 60 % predicted or FEV1 ≥ 60 % and < 80 % given that mMRC ≥ 2 and/or CAT ≥ 10
• PI max < 60 cm H2O
• serum-25(OH)D ≤ 50 nmol/L
• suitable for supervised training in hospital as judged by the physiotherapist
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E.4 | Principal exclusion criteria |
• all contraindications /hypersensitivity to vitamin D3
• hypercalcemia (serum-Ca > 2.65 mmol/L)
• primary hyperparathyroidism (hypercalcemia combined with PTH > 45 ng/L, reference 10-65 ng/L)
• GFR, assessed by serum-cystatin C, < 45 mL/min/1.73 m2
• orthopedic, neurologic or mental impairment that would limit physical training
• exacerbation of COPD and/or airway infection within 2 weeks prior to inclusion
• significant anemia defined as hemoglobin < 110 g/L
• recent myocardial infarct defined as < 6 months prior to inclusion
• other serious disease (e.g. asystoli, stroke etc) that might hinder physical training as judged by the pysician
• sarcoidosis or any other granuloma-forming inflammatory disease
• treatment for neoplastic disease within the last 5 yrs
• expected survival < 6 months
• participation in supervised at hospital physical training finalized within the last 12 months
• ongoing treatment with drugs that interact with vitamin D3 supplementation, e.g. cardiac glycosides, bensotiadiazin derivatives, phenytoin, barbiturates, rifampicin, isoniazid, orlistat and cholestyramine
• participation in another interventional study within the last 12 months
• previous participation in the present study
• all contraindications to MR
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary outcome measure is strength of breathing muscles measured as maximal inspiratory pressure (MIP) after bronchodilation. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
13 weeks after inclusion (study visit 4) |
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E.5.2 | Secondary end point(s) |
• strength of breathing muscles after bronchdilation measured as MEP and SNIP
• muscle strength of dominant leg and arm (measured as peak torque)
• maximal oxygenation capacity (VO2max) and endurance measured with ISWT and ESWT
• lung volumes at rest (FEV1 och FVC) after bronchodilation
• Balance (SBPR)
• muscle metabolism in the quadriceps muscle of the dominant leg before, during and after standardized exercise applying 31P-MRS
• Quantification of muscle mass and fat in the dominant leg using MR
• QoL (SGRQ)
• COPD symptoms (mMRC and CAT)
• Fatigue (MFI-20 and D-FIS)
• Physical activity (IPAQ-S)
• Anxiety and depression (HADS)
• iBODE index (a product of BMI, FEV1 % of predicted, mMRC and ISWT)
• Biological variables for systemic inflammation, oxidative stress and muscle- and bone pathology
• Serum-25(OH)D before and after treatment with study medications
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
13 and 14 weeks after inclusion (study visits 4 and 5) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |