Normast3 for Adults With Diabetic Polyneuropathy

NCT07689214 | Recruiting

• 1 other identifier: NORM3_DPN
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Diabete Type 2

Keywords

neuropathic pain; diabetic neuropathy; autonomic nervous system

Outcome Measures

Primary Outcomes (1)

• 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: Baseline to Week 12

Secondary Outcomes (8)

• Change in autonomic system function (sweat glands) at Week 12

  Baseline to Week 12

• Change in R-R variability at rest Week 12

  Baseline to Week 12

• Change in autonomic innervation density at Week 12

  Baseline to Week 12

• Change in autonomic system function (sweat glands) at Week 24

  Baseline to Week 24

• Change in clinical sensory testing outcomes at Week 12

  Baseline to Week 12

Other Outcomes (6)

• Change in Patient Global Impression of Change (PGIC) at Week 12

  Baseline to Week 12

• Change in Patient Global Impression of Change (PGIC) at Week 24

  Baseline to Week 24

• Percentage of patients achieving Pain reduction ≥50% at Week 12

  Baseline to Week 12

Study Arms (2)

Normast3

EXPERIMENTAL

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

placebo

PLACEBO COMPARATOR

Participants will receive placebo tablets twice daily, after lunch and after dinner, for 12 weeks, in addition to standard diabetes care.

Dietary Supplement: Placebo

Interventions

Placebo DIETARY_SUPPLEMENT

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.

placebo

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 DIETARY_SUPPLEMENT

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.

Normast3

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of mixed-fiber diabetic polyneuropathy Provision of signed and dated informed consent 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

Sponsors & Collaborators

• University of Roma La Sapienza: lead

Study Sites (1)

Department of Human Neuroscience

Rome, Italy, 00185, Italy

RECRUITING

Related Publications (8)

• Tesfaye S, Boulton AJ, Dyck PJ, Freeman R, Horowitz M, Kempler P, Lauria G, Malik RA, Spallone V, Vinik A, Bernardi L, Valensi P; Toronto Diabetic Neuropathy Expert Group. Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments. Diabetes Care. 2010 Oct;33(10):2285-93. doi: 10.2337/dc10-1303.

  PMID: 20876709 BACKGROUND

• Oaklander AL, Nolano M. Scientific Advances in and Clinical Approaches to Small-Fiber Polyneuropathy: A Review. JAMA Neurol. 2019 Oct 1;76(10):1240-1251. doi: 10.1001/jamaneurol.2019.2917.

  PMID: 31498378 BACKGROUND

• Lefrandt JD, Smit AJ, Zeebregts CJ, Gans RO, Hoogenberg KH. Autonomic dysfunction in diabetes: a consequence of cardiovascular damage. Curr Diabetes Rev. 2010 Nov;6(6):348-58. doi: 10.2174/157339910793499128.

  PMID: 20879972 BACKGROUND

• Kles KA, Vinik AI. Pathophysiology and treatment of diabetic peripheral neuropathy: the case for diabetic neurovascular function as an essential component. Curr Diabetes Rev. 2006 May;2(2):131-45. doi: 10.2174/157339906776818569.

  PMID: 18220622 BACKGROUND

• Impellizzeri D, Peritore AF, Cordaro M, Gugliandolo E, Siracusa R, Crupi R, D'Amico R, Fusco R, Evangelista M, Cuzzocrea S, Di Paola R. The neuroprotective effects of micronized PEA (PEA-m) formulation on diabetic peripheral neuropathy in mice. FASEB J. 2019 Oct;33(10):11364-11380. doi: 10.1096/fj.201900538R. Epub 2019 Jul 25.

  PMID: 31344333 BACKGROUND

• Impellizzeri D, Bruschetta G, Cordaro M, Crupi R, Siracusa R, Esposito E, Cuzzocrea S. Micronized/ultramicronized palmitoylethanolamide displays superior oral efficacy compared to nonmicronized palmitoylethanolamide in a rat model of inflammatory pain. J Neuroinflammation. 2014 Aug 28;11:136. doi: 10.1186/s12974-014-0136-0.

  PMID: 25164769 BACKGROUND

• England JD, Gronseth GS, Franklin G, Miller RG, Asbury AK, Carter GT, Cohen JA, Fisher MA, Howard JF, Kinsella LJ, Latov N, Lewis RA, Low PA, Sumner AJ. Distal symmetrical polyneuropathy: definition for clinical research. Muscle Nerve. 2005 Jan;31(1):113-23. doi: 10.1002/mus.20233.

  PMID: 15536624 BACKGROUND

• Bartolucci ML, Marini I, Bortolotti F, Impellizzeri D, Di Paola R, Bruschetta G, Crupi R, Portelli M, Militi A, Oteri G, Esposito E, Cuzzocrea S. Micronized palmitoylethanolamide reduces joint pain and glial cell activation. Inflamm Res. 2018 Oct;67(10):891-901. doi: 10.1007/s00011-018-1179-y. Epub 2018 Aug 18.

  PMID: 30121836 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Neuralgia; Diabetic Neuropathies

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Diabetes Complications

Study Officials

• andrea truini, full professor

  department of human neuroscience, sapienza university

  PRINCIPAL INVESTIGATOR

Central Study Contacts

andrea truini, Full Professor

CONTACT

+39649914122; andrea.truini@uniroma1.it

caterina m leone, assistant professor

CONTACT

+39649914122; caterina.leone@uniroma1.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator - Head of the Neuromuscular Disease Unit

Model Details: This is a single-centre, randomized, double-blind, placebo controlled, parallel group study

Study Record Dates

• First Submitted: June 23, 2026
• First Posted: July 8, 2026
• Study Start: July 17, 2024
• Primary Completion: July 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: July 8, 2026

Record last verified: 2026-06

Locations

IT (1)