An interventional study of Normast® 3 - a food for special medical purposes (FSMP) containing co-micronized palmitoylethanolamide (PEA) with rutin and hydroxytyrosol. It is designed to support the management of diabetic polyneu and Placebo in Diabete Type 2, sponsored by University of Roma La Sapienza. Recruiting at 1 site in Italy. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2026-07-08.
Sponsored by University of Roma La Sapienza · Not applicable, Interventional, and Treatment
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.
10,371 studies on the registry are indexed under Diabetes Mellitus, Type 2; 1,406 are open to participants now.
This study's planned enrollment of 40 is below the median of 80 across 8,350 interventional studies indexed under Diabetes Mellitus, Type 2.
Browse Diabetes Mellitus, Type 2 studies →University of Roma La Sapienza is the lead sponsor of 398 studies on the registry; 56 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Diagnosis of mixed-fiber diabetic polyneuropathy Provision of signed and dated Willingness to comply with all study procedures and availability for the duration of the study Male or female participants aged 18 to 80 years Ability to take oral medication Stable pharmacological treatment during the 3 months before enrollment
Exclusion Criteria:
Concomitant peripheral or central nervous system disease that could interfere with the study objectives Conditions other than diabetes that could affect the peripheral nervous system, including vitamin B12 deficiency, kidney failure, previous neurotoxic therapies, thyroid disease, diseases, or familial amyloidosis Cognitive impairment Major psychiatric comorbidities Inflammatory rheumatic diseases Pain due to conditions other than diabetic polyneuropathy disease or condition that could affect efficacy or safety assessments or otherwise preclude study participation, in the investigator's judgment Evidence or history of alcohol or drug abuse, including opioids, amphetamines, benzodiazepines, or cannabinoids Known or suspected unwillingness or inability to comply with the trial protocol or study instructions Inability to communicate meaningfully with trial site staff, including insufficient language skills Pregnancy or lactation Any other reason for exclusion according to the investigator's judgment
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants will receive Normast® 3 tablets twice daily, after lunch and after dinner, for 12 weeks, in addition to standard diabetes care.
Dietary Supplement: Normast® 3 - a food for special medical purposes (FSMP) containing co-micronized palmitoylethanolamide (PEA) with rutin and hydroxytyrosol. It is designed to support the management of diabetic polyneu
Participants will receive placebo tablets twice daily, after lunch and after dinner, for 12 weeks, in addition to standard diabetes care.
Dietary Supplement: Placebo
Normast® 3 is a food for special medical purposes (FSMP) containing co-micronized palmitoylethanolamide (PEA) with rutin (5:1) and hydroxytyrosol. Each tablet provides 360 mg PEA/rutin and 15 mg hydroxytyrosol. The product is formulated to target neuroinflammation and vascular dysfunction involved in diabetic polyneuropathy. In this study, participants will take one tablet twice daily (after lunch and after dinner) for 12 weeks, in addition to their standard diabetes care.
Placebo tablets are visually and taste-matched to Normast® 3 but contain no active ingredients. Each tablet is composed of inert excipients (mainly microcrystalline cellulose and other standard tablet components). Participants will take one placebo tablet twice daily (after lunch and after dinner) for 12 weeks, in addition to their standard diabetes care.
Change in average daily pain intensity
Description: Change from baseline to Week 12 in the weekly average of participants' daily pain intensity scores, measured using the 0-10 Numeric Rating Scale (NRS), where 0 = no pain and 10 = worst possible pain. Safety Issue: No
Time frame: Time Frame: Baseline to Week 12
Change in autonomic system function (sweat glands) at Week 12
Percentage change from baseline in the number of activated sweat glands, assessed with sudomotor function testing (volume of sweat produced expressed as mcl/cm2/min), in the Normast® 3 group compared to the placebo group.
Time frame: Baseline to Week 12
Change in R-R variability at rest Week 12
Percentage change from baseline in R-R variability at rest after treatment (expressed as total heart rate variability power in milliseconds squared), comparing the Normast® 3 group to the placebo group.
Time frame: Baseline to Week 12
Change in autonomic innervation density at Week 12
Percentage change from baseline in piloerector muscle autonomic innervation density, measured by skin biopsy and immunostaining, in the Normast® 3 group compared to the placebo group.
Time frame: Baseline to Week 12
Change in autonomic system function (sweat glands) at Week 24
Percentage change from baseline in the number of activated sweat glands, assessed with sudomotor function testing (volume of sweat produced expressed as mcl/cm2/min), in the Normast® 3 group compared to the placebo group.
Time frame: Baseline to Week 24
Change in clinical sensory testing outcomes at Week 12
Change from baseline in QST sensory profile in the Normast® 3 group compared to the placebo group.
Time frame: Baseline to Week 12
Change in R-R variability during deep breathing at Week 12
Percentage change from baseline in R-R variability during paced deep breathing (expressed as difference in heart rate between maximum inspiration and minimum expiration), after treatment, comparing the Normast® 3 group to the placebo group.
Time frame: Baseline to week 12
Change in Valsalva ratio at Week 12
Change from baseline in Valsalva ratio. Valsalva ratio is a cardiovascular autonomic test measure used to assess parasympathetic/vagal heart-rate control. It is calculated during the Valsalva manoeuvre as: Valsalva Ratio = Maximum Heart Rate During/Immediately After Straining ÷ Minimum Heart Rate After Release
Time frame: Baseline to week 12
Change LF/HF ratio
Change from baseline in LF/HF ratio, derived from ECG R-R interval recordings after treatment compared to placebo
Time frame: Baseline to 12 week
Change in Patient Global Impression of Change (PGIC) at Week 12
Percentage of participants in the Normast® 3 group reporting an improvement of at least 2 points on the Patient Global Impression of Change (PGIC) (a 7-point patient-rated scale assessing perceived change in overall condition, ranging from 1 = very much improved to 7 = very much worse) scale at Week 12, compared to the placebo group.
Time frame: Baseline to Week 12
Change in Patient Global Impression of Change (PGIC) at Week 24
Percentage of participants in the Normast® 3 group reporting an improvement of at least 2 points on the Patient Global Impression of Change (PGIC) (a 7-point patient-rated scale assessing perceived change in overall condition, ranging from 1 = very much improved to 7 = very much worse) scale at Week 24, compared to the placebo group.
Time frame: Baseline to Week 24
Percentage of patients achieving Pain reduction ≥50% at Week 12
Percentage of participants achieving at least 50% reduction in average daily pain intensity (on a numerical rating scale from 0 to 10) from baseline at Week 12 in the Normast® 3 group, compared to the placebo group.
Time frame: Baseline to Week 12
Percentage of patients achieving Pain reduction ≥50% at Week 24
Percentage of participants achieving at least 50% reduction in average daily pain intensity(on a numerical rating scale from 0 to 10) from baseline at Week 24 in the Normast® 3 group, compared to the placebo group.
Time frame: Baseline to Week 24
Percentage of patients achieving Pain reduction ≥30% at Week 12
Percentage of participants achieving at least 30% reduction in average daily pain intensity (on a numerical rating scale from 0 to 10) from baseline at Week 12 in the Normast® 3 group, compared to the placebo group
Time frame: Baseline to Week 12
Percentage of patients achieving Pain reduction ≥30% at Week 24
Percentage of participants achieving at least 30% reduction in average daily pain intensity (on a numerical rating scale from 0 to 10) from baseline at Week 24 in the Normast® 3 group, compared to the placebo group.
Time frame: Baseline to Week 24
Plan to share: Undecided — De-identified individual participant data (IPD) underlying the study results (including text, tables, figures, and appendices) might be made available to qualified researchers upon reasonable request to the sponsor, after publication of the primary study results. Data will be shared for purposes of meta-analyses or other scientific research, in compliance with applicable data protection regulations.
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