Normast3 for Adults With Diabetic Polyneuropathy
A Randomized, Placebo-Controlled, Double-Blind, Single-Center Clinical Trial to Evaluate the Efficacy of Normast3 in Adult Patients With Diabetic Polyneuropathy
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).
Přehled studie
Postavení
Podmínky
Detailní popis
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.
Typ studie
Zápis (Odhadovaný)
Fáze
- Nelze použít
Kontakty a umístění
Studijní kontakt
- Jméno: andrea truini, Full Professor
- Telefonní číslo: +39649914122
- E-mail: andrea.truini@uniroma1.it
Studijní záloha kontaktů
- Jméno: caterina m leone, assistant professor
- Telefonní číslo: +39649914122
- E-mail: caterina.leone@uniroma1.it
Studijní místa
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Italy
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Rome, Italy, Itálie, 00185
- Nábor
- Department of Human Neuroscience
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Kontakt:
- Caterina maria
- Telefonní číslo: 3356866757
- E-mail: caterinamaria.leone@gmail.com
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Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
- Dospělý
- Starší dospělý
Přijímá zdravé dobrovolníky
Popis
Inclusion Criteria:
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
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, autoimmune diseases, or familial amyloidosis Cognitive impairment Major psychiatric comorbidities Inflammatory rheumatic diseases Pain due to conditions other than diabetic polyneuropathy Clinically significant 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
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Čtyřnásobek
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
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Experimentální: Normast3
Participants will receive Normast® 3 tablets twice daily, after lunch and after dinner, for 12 weeks, in addition to standard diabetes care.
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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.
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Komparátor placeba: placebo
Participants will receive placebo tablets twice daily, after lunch and after dinner, for 12 weeks, in addition to standard diabetes care.
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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.
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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
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Change in average daily pain intensity
Časové okno: Time Frame: Baseline to Week 12
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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
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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Change in autonomic system function (sweat glands) at Week 12
Časové okno: Baseline to Week 12
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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.
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Baseline to Week 12
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Change in R-R variability at rest Week 12
Časové okno: Baseline to Week 12
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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.
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Baseline to Week 12
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Change in autonomic innervation density at Week 12
Časové okno: Baseline to Week 12
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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.
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Baseline to Week 12
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Change in autonomic system function (sweat glands) at Week 24
Časové okno: Baseline to Week 24
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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.
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Baseline to Week 24
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Change in clinical sensory testing outcomes at Week 12
Časové okno: Baseline to Week 12
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Change from baseline in QST sensory profile in the Normast® 3 group compared to the placebo group.
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Baseline to Week 12
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Change in R-R variability during deep breathing at Week 12
Časové okno: Baseline to week 12
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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.
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Baseline to week 12
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Change in Valsalva ratio at Week 12
Časové okno: Baseline to week 12
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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 |
Baseline to week 12
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Change LF/HF ratio
Časové okno: Baseline to 12 week
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Change from baseline in LF/HF ratio, derived from ECG R-R interval recordings after treatment compared to placebo
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Baseline to 12 week
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Další výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Change in Patient Global Impression of Change (PGIC) at Week 12
Časové okno: Baseline to Week 12
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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.
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Baseline to Week 12
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Change in Patient Global Impression of Change (PGIC) at Week 24
Časové okno: Baseline to Week 24
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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.
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Baseline to Week 24
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Percentage of patients achieving Pain reduction ≥50% at Week 12
Časové okno: Baseline to Week 12
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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.
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Baseline to Week 12
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Percentage of patients achieving Pain reduction ≥50% at Week 24
Časové okno: Baseline to Week 24
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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.
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Baseline to Week 24
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Percentage of patients achieving Pain reduction ≥30% at Week 12
Časové okno: Baseline to Week 12
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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
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Baseline to Week 12
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Percentage of patients achieving Pain reduction ≥30% at Week 24
Časové okno: Baseline to Week 24
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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.
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Baseline to Week 24
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Spolupracovníci a vyšetřovatelé
Sponzor
Vyšetřovatelé
- Vrchní vyšetřovatel: andrea truini, full professor, department of human neuroscience, sapienza university
Publikace a užitečné odkazy
Obecné publikace
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Primární dokončení (Odhadovaný)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
- Bolest
- Neurologické projevy
- Onemocnění endokrinního systému
- Nemoci nervového systému
- Neuromuskulární onemocnění
- Metabolické choroby
- Onemocnění periferního nervového systému
- Poruchy metabolismu glukózy
- Diabetes Mellitus
- Komplikace diabetu
- Patologické stavy, příznaky a symptomy
- Nutriční a metabolické nemoci
- Příznaky a symptomy
- Diabetes mellitus, typ 2
- Neuralgie
- Diabetické neuropatie
Další identifikační čísla studie
- NORM3_DPN
Plán pro data jednotlivých účastníků (IPD)
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Popis plánu IPD
Informace o lécích a zařízeních, studijní dokumenty
Studuje lékový produkt regulovaný americkým FDA
Studuje produkt zařízení regulovaný americkým úřadem FDA
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