E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
ENDOTHELIAL DYSFUNCTION AND BONE REMODELLING |
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E.1.1.1 | Medical condition in easily understood language |
SMALL VESSEL BLOOD FLOW AND BONE METABOLISM |
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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 | 16.1 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10067225 |
E.1.2 | Term | Biochemical markers of bone metabolism |
E.1.2 | System Organ Class | 100000004848 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10048554 |
E.1.2 | Term | Endothelial dysfunction |
E.1.2 | System Organ Class | 10047065 - Vascular 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 assess the role of nitrates in improving microvascular blood flow |
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E.2.2 | Secondary objectives of the trial |
To determine whether nitrates can cause an increase in bone formation markers and reduction in bone resorption markers. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Females and males aged between 40-75 years • A diagnosis of type 2 DM based on one of the following criteria (ADA - 2010): - Fasting plasma glucose (FPG) >= 126 mg/dL (7.0 mmol/L) or - 2-h plasma glucose >= 200 mg/dl (11.1 mmol/L) during an OGTT or - Classic symptoms of hyperglycemia or hyperglycemic crisis with a random plasma glucose >= 200 mg/dL (11.1 mmol/L).
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E.4 | Principal exclusion criteria |
• At screening, age below 40 years and above 75 years. • Pregnancy or lactation • Type 1 diabetes mellitus (patients with a history of ketoacidosis, age of onset of DM before 25 years of age, BMI <21 kg/m2 and use of insulin without a concomitant oral hypoglycemic agent) • Patients with uncontrolled hypertension (systolic blood pressure [SBP] > 160/90 mmHg) or hypotension (SBP of <=100 mm Hg or a diastolic BP of >= 110 mm Hg) at screening. • History of hypersensitivity to nitrates • History of raised intracranial pressure • History of cardiovascular disease (ischaemic heart disease, previous stroke and severe peripheral vascular disease [Ankle brachial pressure index - ABPI< 0.7]) • History of general systemic illness including cardiac, hepatic or renal insufficiency • Patients with clinical nephropathy (24 hour protein > 0.5g or dipstix protein +) or renal failure (serum creatinine > 130 µmol/l). • History of migraine headaches • History of Paget’s disease and other metabolic bone disorders • History of coeliac or inflammatory bowel disease • History of multiple myeloma or cancer • History of nitrate use for cardiac conditions • History of glucocorticoid intake within the last 3 months • History of hormone replacement therapy in the last 12 months • History of treatment with SERM (selective estrogen receptor modulator) • History of treatment with thiazolidinedione • History of anticonvulsant use • History of past or current treatment for osteoporosis • History of bisphosphonate therapy within the last 3 years
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E.5 End points |
E.5.1 | Primary end point(s) |
IMPROVEMENT IN MICROVASCULAR BLOOD FLOW |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
IMPROVEMENT IN BONE MARKERS |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | Yes |
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 | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 1 |
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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LVLS
THE STUDY MAY BE PREMATURELY DISCONTINUED IF THE PATIENTS DEVELOP ADVERSE EFFECTS TOWARDS THE STUDY MEDICATION |
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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 | 6 |
E.8.9.1 | In the Member State concerned days | |