Diabetic Polyneuropathy MedDRA version: 8.1 Level: LLT Classification code 10012685 Term: Diabetic polyneuropathy
Conditions
Interventions
Trade Name: ACTOVEGIN "Nycomed" 20 %-Infusionsflasche
Pharmaceutical Form: Solution for infusion
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intra
Sponsors
Nycomed Austria GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Has the patient given informed consent according to local requirements before any trial related activities? A trial related activity is any procedure that would not have been performed during the routine management of the patient. 2. Is the patient aged = 18 to = 65 years? 3. Does the patient suffer from type 2 diabetes mellitus? 4. Has the patient evidence of symptomatic diabetic peripheral polyneuropathy, i.e. TSS =6 and NIS-LL = 2? 5. Is the patient’s VPT measured to = 30V? 6. Has the patient adequate circulation to the foot as evidenced by a palpable pulse on posterior tibialis artery and dorsal artery of foot? 7. Is the HbA1C level less than 10%? 8. Is the patient able to make frequent clinic visits over the trial period? For patients receiving tricyclic antidepressants, anticonvulsants, mexiletine or neuroleptics as treatment of neuropathic pain: 9. Has the regimen been stable within the last month? For female patients of childbearing potential (childbearing potential is considered until menopause has lasted more than 12 months): 10. Does the patient use an acceptable contraceptive method (hormonal pills, patches, implants, injections or intrauterine device)? 11. Is the pregnancy test negative before the 1st dose of IMP? (Surgically hysterectomised and surgically successfully sterilized females may be included on the same conditions as male patients). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Does the patient suffer from known allergy towards Actovegin or similar preparations? 2. Has the patient asymmetrical neuropathy of the trunk or proximal lower limbs? 3. Does the patient suffer from diabetic foot ulceration or infections? 4. Does the patient suffer from diabetic amyotrophy? 5. Does the patient suffer from decompensated cardiac insufficiency, pulmonary oedema, oliguria, anuria, generalised oedema? 6. Does the patient suffer from polyneuropathy due to other underlying causes? 7. Has the patient been hospitalised due to diabetic polyneuropathy within the last month? 8. Has the patient participated in any other trial with an Investigational Medicinal Product (IMP) or device within 30 days before inclusion in this trial? 9. Has the patient ever used medications that may be etiological factors for neuropathy, such as isoniazid, nitrofurantoin, vincristine and phenytoin? 10. Has the patient used cerebrolysin or a-lipoic acid or received Transcutaneous Electric Nerve Stimulation (TENS) or acupuncture within the last month? 11. Has the patient received opiates as treatment of his / her diabetic polyneuropathy within the last month? 12. Does the patient suffer from any malignancy? 13. Is the patient nursing? 14. Does the patient suffer from any mental, psychiatric or other conditions that may compromise data collection and understanding of written and verbal information given in the trial? 15. Does the patient suffer from present and / or previous chronic alcohol abuse? 16. Is there any anamnestic evidence of hypothyroidism? 17. Is there any anamnestic evidence of vitamin B12 deficiency? 18. Does the patient suffer from an impaired renal function with high blood urea nitrogen (BUN) and / or increased serum creatinine (>120 µmol/L)?
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate efficacy and safety of Actovegin® (Actovegin) versus placebo given as intravenous (i.v.) infusions once daily for 20 days, followed by oral treatment for 140 days in patients with symptomatic diabetic peripheral polyneuropathy.;Secondary Objective: ;Primary end point(s): Average of TSS over the treatment period calculated by Area Under the Curve (AUC), divided by the treatment period in number of days. According to recommendations (30), positive neuropathic sensory symptoms can serve as important endpoints for controlled clinical trials in diabetic polyneuropathy, since they are symptoms of which patients complain and for which patients come to doctors seeking relief. In tertiary neuromuscular practice, painful neuropathy is among the most common reasons for referral. The TSS range from 0 (no symptoms) to 14.64 points (all symptoms and [almost] continuously present between the groups receiving Actovegin and placebo (31). Average of the VPT over the treatment period using the same methods as for the TSS using Bio-Thesiometer, which is a quantitative sensory testing device. According to the guidelines for clinical investigations for medicinal products in the treatment of diabetes mellitus (32), efficacy should be based on clinical symptoms and signs, however, quantitative sensory tests, e.g. for vibration, can be supportive. There are published data, suggesting that test of VPT can be used as a clinical predictor for foot ulceration in diabetic patients with established neuropathy (33), and it is anticipated that vibratory sensations are conveyed by large diameter fibers, while neuropatic pain primarily conveyed by small-fiber sensations (34). There are data indicating that VPT examinations obtained with a simple, relatively inexpensive device, such as Bio- Thesiometer, are comparable to those obtained using more elaborate equipment and testing methods (35). | — |
Countries
Austria
Outcome results
None listed