E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Type II diabetes mellitus |
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E.1.1.1 | Medical condition in easily understood language |
Patients with Type II diabetes mellitus have a problem with their body which causes blood glucose (sugar) levels to rise higher than normal. |
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E.1.1.2 | Therapeutic area | Body processes [G] - Metabolic Phenomena [G03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067585 |
E.1.2 | Term | Type 2 diabetes mellitus |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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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 |
To investigate the impact of one year therapy with minocycline on MMP-9 in patients with with Type 2 diabetes and the MMP-9, 1562 C>T promoter single nucleotide polymorphism
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E.2.2 | Secondary objectives of the trial |
To determine the impact of one year therapy with tetracyclines (minocycline) on markers of inflammation and collagen turnover in patients with Type 2 diabetes and the MMP-9, 1562 C>T promoter single nucleotide polymorphism
To assess the impact of one year therapy with tetracyclines (minocycline) on cardiovascular function using ABPM, Pulse Wave Velocity, Retinopathy Assessments, Cardiac MRI and Doppler Echocardiography. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Treated Type 2 diabetes > 6 months 1562 C>T MMP-9 single nucleotide promoter polymorphism Clinically stable (on same treatment for > 1 month) Willing and able to provide informed consent
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E.4 | Principal exclusion criteria |
1. Age < 18 years at the time of randomisation 2. Tetracycline hypersensitivity or other contraindications to minocycline therapy, e.g. use during pregnancy or breast feeding or obstructive oesophageal disorders such as stricture or achalasia. 3. Pre-menopausal women (defined as last menstrual period <12 months earlier). (i.e. postmenopausal women only will be eligible for enrolment. Postmenopausal is defined as 12 months with no menses without an alternative medical cause). 4. Change in diuretics within one month or recent admission for acute decompensated heart failure/cardiovascular event (e.g. ischaemia) < 3 months 5. Haemodynamically severe valvular heart disease 6. Evidence of significant inflammatory disease, connective tissue disease, hepatic disease, metabolic bone disease which may alter inflammation and parameters of matrix turnover and collagen metabolism 7. Hypertrophic, restrictive or constrictive cardiomyopathy 8. Clinically significant pulmonary disease as evidenced by hospitalisations or use of oral corticosteroids for pulmonary decompensation within 12 months, or requirement for home O2 or significant fibrosis 9. Severe anaemia (Haemoglobin <8.0g/dL) 10. Severe renal dysfunction (GFR < 30 mL/min/1.73m2) 11. Subjects with hepatic dysfunction (Any LFT > 3 Upper Limit of Normal) 12. Gastro-oesophageal reflux disease 13. Recent trauma or surgery (<6 months) 14. Malignancy 15. Systemic lupus erythematous (SLE) 16. Myasthenia gravis 17. Subjects with contraindications to MRI (NOTE: if a patient has a contraindication to MRI but is otherwise eligible for enrolment, they may be recruited onto the study. However, they will be excluded from undergoing MRI and this will be clearly highlighted in the patients CRF) a. Hypersensitivity to gadolinium containing contrast agents b. Brain Aneurysm Clip c. Implanted neural stimulator d. Implanted cardiac pacemaker or defibrillator e. Cochlear implant f. Ocular foreign body (e.g. metal shavings) g. Other implanted medical devices: (e.g. Swan Ganz catheter) h. Insulin pump i. Metal shrapnel or bullet.
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in serum MMP-9 level following one year therapy with tetracyclines (minocycline) in patients with with Type 2 diabetes and the MMP-9, 1562 C>T promoter single nucleotide polymorphism.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline (time zero), six months and twelve months |
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E.5.2 | Secondary end point(s) |
Change in serum markers of inflammation, endothelial function and collagen turnover following one year therapy with tetracyclines (minocycline)
Change in ABPM, Pulse Wave Velocity, Retinopathy Assessments (e.g. Visual Acuity) and markers of cardiac structure and function on Cardiac MRI and Doppler Echocardiography.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Baseline (time zero), six months and twelve months (retinopathy and MRI at baseline and 12 months only) |
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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 | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
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) | 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 | Yes |
E.8.1.2 | Open | Yes |
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.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | |
E.8.9.1 | In the Member State concerned months | 12 |
E.8.9.1 | In the Member State concerned days | |