E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diabtes and its complications, painful neuropathy |
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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 |
To determine the effect of pregabalin on cerebral pain processing and sensory perception thresholds in diabetic patients with Painful Diabetic Neuropathy. |
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E.2.2 | Secondary objectives of the trial |
To determine the effect of pregabalin on pain-related brain activity at rest and during noxious thermal stimulation using blood oxygen level-dependent (BOLD) contrast functional magnetic resonance imaging (fMRI)
To determine the effects of pregabalin on cerebral evoked potential (EP) response at rest and during noxious thermal stimulation
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Type 1 or type 2 diabetes as defined by the World Health Organization Classification. 2. Duration of diabetes of at least 5 years. 3. The HbA1c should be <9% with <1% fluctuation of HbA1c levels over the past 6 months. 4. Age between 18 and 70 years. 5. Women of childbearing potential must be using an acceptable method of contraception to prevent pregnancy when they are enrolled in the study and must agree to continue to practice an acceptable method of contraception for the duration of their participation in the study. 6. Must be meet the specified criteria for PDN (see below) and have no risk factors for other causes for neuropathy 7. Willingness to sign the Center for Research Ethics Committee (COREC) approved informed consent form
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E.4 | Principal exclusion criteria |
1. Nursing mothers, pregnant women (excluded by a negative pregnancy test). 2. Patients with a history of drug or alcohol dependence in the last 5 years 3. Patients with severe systemic disease other than diabetes which has as a recognized complication neuropathy or severe chronic pain 4. Patients with symptoms of neuropathic pain in the upper limbs alone 5. Significant changes in skin conditions in the areas to be tested which could alter sensation. 6. Patients currently taking medications that could affect symptoms of painful DN except acetominophen (up to 3g/d) or aspirin (up to 325 mg/d). 7. Patients experiencing an increase in pain after analgesic medication washout to levels which would, in the view of the PI, require prohibited analgesic therapy within a 6 wk period. 8. Patients whose creatinine clearance is less than 70 ml/min or have significant hepatic disease (AST, ALT, γGT >2 times upper limit for normal). Patients with TSH outside normal limits 9. Patients with a history of previous kidney, pancreas or cardiac transplantation. 10. Serious or unstable medical or psychological state that may interfere with study participation. 11. Patients having taken other systemic investigational drugs (especially for neuropathy) or initiating a new or experimental insulin delivery device within 3 months of starting the study. 12.patients with a hypersensivity to pregabalin 13. Patients who refuse to sign the informed consent.
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E.5 End points |
E.5.1 | Primary end point(s) |
A 6 week placebo-controlled, cross-over clinical study will be conducted in patients with PDN. Subjects who are eligible for the study will be randomized to one of two treatment groups: Group 1: Pregabalin (75 mg bd) (Pfizer Pharmaceutical Company), or Group 2: matched oral placebos for 2 weeks, then undergo a 2 week washout period and then cross over to the alternative therapy for 2 weeks. Weekly Activities: Subjects will complete pain diaries and sleep interference scores on a weekly basis. All subjects will be reviewed at 2 weekly intervals when compliance will be reassessed.
At two weekly visits, the following procedures will be performed: Assessment of compliance; blood pressure and pulse evaluation; evaluation of current medications; collection of study drug; recording of adverse symptoms/events. Collection of data from weekly pain diaries and sleep interference scores. SF-MMPQ will be completed at each visit.
At the two and six weekly visits, the following additional procedures will be performed: BOLD-contrast fMRI and somatosensory psychophysics will be performed and cerebral EP responses to thermal noxious stimulation recorded. laser doppler ans skin biopsies will also be undertaken. Clinical and Global Impression of Change questionnaires will be completed. A blood draw will include glycaemic (glucose, HbA1c) measurements.
The follow-up evaluation: All patients will be contacted 4 wk after the final visit and study drug withdrawal in order to monitor response to discontinuation of treatment or regression or adverse events.
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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 | Yes |
E.6.4 | Safety | Yes |
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 | 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) | 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 | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
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.8.3 |
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 | Information not present in EudraCT |
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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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 | 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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |