Normast3 for Adults With Diabetic Polyneuropathy

Overview

The goal of this clinical trial is to find out if a new supplement called Normast® 3 can help reduce nerve pain and improve nerve function in adults with diabetic polyneuropathy (DPN). DPN is a common complication of diabetes that damages nerves, often causing burning, tingling, or stabbing pain, as well as problems with the autonomic nervous system, which controls things like sweating and heart rate. The main questions this study aims to answer are: Does taking Normast® 3 lower daily pain levels after 12 weeks of treatment? Does it improve the function of small nerve fibers and the autonomic nervous system compared with a placebo (a look-alike tablet with no active ingredients)? Study design This is a randomized, double-blind, placebo-controlled clinical trial. This means participants are randomly assigned to receive either Normast® 3 or placebo, and neither participants nor researchers will know who is receiving which treatment until the study ends. Who can take part About 40 adults aged 18 to 80 who have diabetic polyneuropathy affecting both small and large nerve fibers will be enrolled. Participants must have stable diabetes treatment for at least 3 months and be able to take oral medication. People with other nerve diseases, major psychiatric conditions, or serious health problems will not be able to take part. What participants will do Take Normast® 3 or placebo tablets twice a day for 12 weeks while continuing their usual treatments Complete pain and symptom questionnaires Have neurological examinations including quantitative sensory testing, heart and blood pressure tests, the dynamic sweat test, and small skin biopsies to look at intraepidermal nerve fibers Return for follow-up visits at 12 weeks (end of treatment) and 24 weeks (long-term follow-up) Safety and follow-up Researchers will check participants' safety through blood and urine tests and by monitoring any side effects. Participants can stop the study at any time. Where the study takes place This study is being conducted at the Department of Human Neuroscience, Sapienza University of Rome (Italy).

This is a single-center, randomized, double-blind, placebo-controlled, parallel-group clinical trial evaluating Normast® 3 as add-on treatment in adults with diabetic polyneuropathy involving both small and large nerve fibers. The study is designed to assess whether 12 weeks of treatment with Normast® 3 improves neuropathic pain and selected clinical, psychophysical, autonomic, and morphometric markers of nociceptive and autonomic nerve fiber function compared with placebo. Approximately 40 participants will be randomized in a 1:1 ratio to receive either Normast® 3 or matching placebo for 12 weeks, while continuing stable standard-of-care treatment. Study assessments are performed at baseline, at the end of the 12-week treatment period, and at a 24-week follow-up visit to evaluate persistence of treatment effects. The study population includes adults with diabetic polyneuropathy characterized by symptoms and signs of distal sensory involvement and objective evidence of large- and small-fiber abnormalities. Neurological assessment includes evaluation of negative sensory signs, such as tactile, pinprick, and thermal hypoesthesia, and positive sensory signs, such as spontaneous pain, paroxysmal pain, allodynia, and pinprick hyperalgesia. Quantitative sensory testing is performed at the foot to assess thermal, mechanical, pain, pressure, paradoxical heat, and vibration-related sensory parameters. Autonomic nervous system function is assessed using sudomotor and cardiovascular autonomic testing. Sudomotor function is evaluated through quantitative assessment of activated sweat glands at the distal leg. Cardiovascular autonomic testing includes heart-rate and blood-pressure responses at rest, during paced deep breathing, standing, the Valsalva manoeuvre, and sustained handgrip. Skin biopsy is used to assess small-fiber and autonomic innervation. Samples are obtained from standardized distal and proximal sites and processed using immunofluorescence methods. Morphometric analyses include intraepidermal nerve fiber density, distal-to-proximal nerve fiber density ratio, sweat gland and piloerector muscle autonomic innervation density, and expression patterns of selected nociceptor-related skin biomarkers. Normast® 3 contains palmitoylethanolamide co-micronized with rutin and hydroxytyrosol. The active product and placebo are prepared to be indistinguishable in appearance and administered twice daily. Treatment allocation is concealed from participants and study personnel until completion of the blinded phase, except when unblinding is required for safety reasons. Safety and tolerability are assessed through clinical monitoring, vital signs, laboratory testing, and adverse-event collection during the treatment period. Compliance is assessed by return of used treatment packs at study visits. The total observation period for each participant is approximately 6 months, and the overall study duration is estimated to be approximately 18 months.