E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diabetic painful peripheral 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 |
This study aims to determine whether neuropathic pain in diabetes can be decreased with the use of taurine through subjective pain measures and electrophysiological measurements. |
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E.2.2 | Secondary objectives of the trial |
It's second aim is to determine if the reduction of pain can improve mood and quality of life in patients with diabetes. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria for subjects:
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 <12% 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 painful DN (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 |
Exclusion criteria for subjects:
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 pre-existing cardiovascular disease. Patients with hypoxemic disease. 4. Patients with severe systemic disease other than diabetes which has as a recognized complication neuropathy or severe chronic pain 5. Patients with symptoms of neuropathic pain in the upper limbs alone 6. Significant changes in skin conditions in the areas to be tested which could alter sensation. 7. Subjects with a previous history of neuropathic foot ulceration or Charcot arthropathy 9. Patients currently taking medications that could affect symptoms of painful DN except acetominophen (up to 3g/d) or aspirin (up to 325 mg/d). 10 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 12 wk period. 11. 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 12. Patients with a history of previous kidney, pancreas or cardiac transplantation. 13. Serious or unstable medical or psychological state that may interfere with study participation. 14. 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. 15. Morbidly obese patients (BMI greater than 40). 16. Patients who refuse to sign the informed consent.
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E.5 End points |
E.5.1 | Primary end point(s) |
The proposed design is a randomized, double-blind clinical trial of taurine versus placebo, with the primary outcomes being pain and cold detection threshold.
1. Short-Form McGill-Melzack Pain Questionnaire: A SF-MMPQ is used to determine the effects of taurine treatment on qualitative aspects of pain perception. The SF-MMPQ comprises a sensory score, an affective score and a total score for various pain descriptors; a visual analogue scale (VAS) to assess overall pain intensity and a present pain rating intensity index (PPI). The SF-MMPQ contains 15 descriptions of pain, 11 of which represent the sensory dimension of painful experience and 4 of which represent the affective dimension. Each of these pain descriptions is then ranked by the subject on a 4 point scale and totally within subclasses. The overall intensity of the pain is scored using the 6-point PPI and the VAS. This questionnaire, together with the daily pain diaries, the clinical and patient global assessment of change, forms the basis of the assessment of changes in pain in this study.
2. Mean Sleep Interference Score: Decreased nocturnal pain perception may be associated with improved sleep. This will be assessed using a standardized sleep interference score. Mean sleep interference scores are calculated at baseline (ie the week preceding the randomization visit) and for the final week of the study (between visits B and C). The diary that is utilized for sleep assessment comprises a daily diary with an 11-point Likert-type scale which describes the degree to which the subject’s pain has interfered with sleep during the preceding 24 h. The scale ranges from zero (pain does not interfere with sleep to 10 (pain completely interferes with sleep). The assessment is performed on a daily basis upon awakening. The end-point mean sleep interference score is calculated as the mean score for the last 7 dairy entries while the subject was taking the study drug.
3. Mean Pain Scores from Screening to Study End: The subjects daily diaries are used to compute the mean pain scores in each treatment group from the screening visit to the study end. The daily diary comprises an 11-point Likert-type scale which ranges from 0 (no pain) to 10 (worst possible pain). The degree of neuropathic pain that has been experienced by the subject is rated by selecting a number from 0 to 10. This diary is completed upon awakening. The end-point mean pain score is calculated as the mean score for the last 7 dairy entries while the subject was taking the study drug.
4. Clinical and Patient Global Impression of Change: These measures of global impression of change are evaluated by both the physician and the patient at the final visit. The Clinical Global Impression of Change is a clinician-rated instrument which measures the change in the subjects overall status on a 7-point scale which ranges from 1 (very much improved) to 7 (very much worse). In parallel, the subject completes a Patient Global Impression of Change which measures the subjects overall status using a similar 7-point scale.
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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 | No |
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) | 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 | 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.8.3 |
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 | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
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 subject enrolled in the study. |
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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 | |
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 |