E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
perioperative inflammation in patients undergoing oesophagectomy. |
|
E.1.1.1 | Medical condition in easily understood language |
inflammation following surgery for oesophgeal cancer. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
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 |
The aim of this study is to determine the minimum dose that will effectively replace vitamin D cases in all patients undergoing oesophagectomy. It is important to test the dosing as our patients are very deficient and have defective oesophageal motility. Our dosing escalation study will therefore cover a dose range from 100,000 to 300,000 IU in starting at 100,000 units. Our primary endpoint is restoration of plasma vitamin D levels to above 75nmol/l in all treated cases. |
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E.2.2 | Secondary objectives of the trial |
Secondary outcomes are safety and tolerability data- blood biochemistry, medication related side effects. 2) Plasma vitamin D (25D3) levels over the 14 days after dosing. 3) plasma LL-37 (a downstream vitamin D target) at baseline and on the day of operation. 4) Change in Plasma 1, 25 D3 (the biologically active hormone) from baseline on the day of operation |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Planned transthoracic oesophagectomy for oesophageal carcinoma at a participating centre. • Aged over 16 years on day of first dose of IMP • Ability to give written informed consent to participate in the study. |
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E.4 | Principal exclusion criteria |
• known intolerance of vitamin D • known sarcoidosis, hyperparathyroidism, or nephrolithiasis • taking more than 1000iu/day vitamin D supplementation in the month preceding enrolment • baseline serum corrected calcium >2.65 mmol/L • undergoing haemodialysis • Pregnant or breastfeeding. • Taking cardiac glycoside, carbamazepine, phenobarbital, phenytoin, primidone or long-term immunosuppressant therapy. • Taking oral preparation containing > 10 micrograms vitamin D/day up to 2 months before first dose of IMP. • Diagnosis of COPD with an FEV1 less than 50% predicted or resting oxygen saturations of less 92%. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Plasma vitamin 25D3 level upon the day of oesophagectomy |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
preoperative plasma taken at the start of the operation. |
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E.5.2 | Secondary end point(s) |
1) Safety and tolerability data – blood biochemistry, medication related side effects.2) Plasma 25D3 levels at 7, 10 and 14 days post dose. 3) plasma LL-37 (a downstream vitamin D target) at baseline and on the day of operation. 4) Change in Plasma 1,25 D3 (the biologically active hormone) from baseline on the day of operation |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
at enrollment, preoperative plasma. |
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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 | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
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 | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | No |
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 | 2 |
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
|
The end of the study will be defined as the date of the final day of the final participant undergoing follow-up. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |