Diabete Type 2NCT07689214
Normast3 for Adults With Diabetic Polyneuropathy
A study testing 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 in people with Diabete Type 2, run by University of Roma La Sapienza at 1 site in Italy.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Diabete Type 2
- What is being tested?
- 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
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteItaly
- Study dates
- 17 Jul 2024to Sep 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
Department of Human Neuroscience
Rome, Italy, 00185
Caterina maria, 3356866757, caterinamaria.leone@gmail.com
About this study
Official title: 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:
Read more
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).
Read the detailed description
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.
- Conditions
- Diabete Type 2
- Being tested
- 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
- Keywords
- neuropathic pain, diabetic neuropathy, autonomic nervous system
- Medical subject headings
- Diabetes Mellitus, Type 2, Neuralgia, Diabetic Neuropathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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 polyneuDietary 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.
PlaceboDietary 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.
| Study group | Role | What they receive |
|---|---|---|
| Normast3 | Experimental | Participants will receive Normast® 3 tablets twice daily, after lunch and after dinner, for 12 weeks, in addition to standard diabetes care. Receives: 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. Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Time Frame: Baseline to Week 12
Secondary outcomes (8)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Measured: Baseline to 12 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jul 2026
- Study start17 Jul 2024
- Primary completionJul 2026 (estimated)
- Study completionSep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Diabete Type 2Studies of the same condition, open and under way.
- More trials run by University of Roma La SapienzaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a single-centre, randomized, double-blind, placebo controlled, parallel group study
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Roma La Sapienza
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Andrea Truini, University of Roma La Sapienza
- Investigators
- andrea truini, full professor, Principal investigator, department of human neuroscience, sapienza university
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07689214
- Sponsor's protocol ID
- NORM3_DPN
- Status last verified
- Jun 2026
- First submitted
- 23 Jun 2026
- Last updated
- 8 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- 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.
Publications
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.
PubMed 20876709Oaklander 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.
PubMed 31498378Lefrandt 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.
PubMed 20879972Kles 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.
PubMed 18220622Impellizzeri 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.
PubMed 31344333Impellizzeri 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.
PubMed 25164769England 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.
PubMed 15536624Bartolucci 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.
PubMed 30121836
Study at a glance
From the registry record, last updated by the sponsor on 8 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Placebo-Controlled, Double-Blind, Single-Center Clinical Trial to Evaluate the Efficacy of Normast3 in Adult Patients With Diabetic Polyneuropathy
- ClinicalTrials.gov ID
- NCT07689214
- Acronym / sponsor ID
- NORM3_DPN
- Conditions
- Diabete Type 2
- Keywords
- neuropathic pain, diabetic neuropathy, autonomic nervous system
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- University of Roma La SapienzaUniversity, hospital or other
- Study start
- 17 Jul 2024 (actual)
- Primary completion
- Jul 2026 (estimated)
- Study completion
- Sep 2026 (estimated)
- First posted
- 8 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- This is a single-centre, randomized, double-blind, placebo controlled, parallel group study
| Arm | Type | Receives |
|---|---|---|
| Normast3 | Experimental | 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 polyneuParticipants will receive Normast® 3 tablets twice daily, after lunch and after dinner, for 12 weeks, in addition to standard diabetes care. |
| placebo | Placebo comparator | Dietary Supplement: PlaceboParticipants will receive placebo tablets twice daily, after lunch and after dinner, for 12 weeks, in addition to standard diabetes care. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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
Key exclusion criteria (1 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 polyneuNormast® 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. | Dietary supplement | Normast3 |
| PlaceboPlacebo 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. | Dietary supplement | placebo |
Primary outcome
Change in average daily pain intensity
Time frame: Time Frame: Baseline to Week 12
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
8 secondary outcomes
Change in autonomic system function (sweat glands) at Week 12
Time frame: Baseline to Week 12
Change in R-R variability at rest Week 12
Time frame: Baseline to Week 12
Change in autonomic innervation density at Week 12
Time frame: Baseline to Week 12
Change in autonomic system function (sweat glands) at Week 24
Time frame: Baseline to Week 24
Change in clinical sensory testing outcomes at Week 12
Time frame: Baseline to Week 12
Change in R-R variability during deep breathing at Week 12
Time frame: Baseline to week 12
Change in Valsalva ratio at Week 12
Time frame: Baseline to week 12
Change LF/HF ratio
Time frame: Baseline to 12 week
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jul 2026.
- Background: PubMed 20876709Tesfaye 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.
- Background: PubMed 31498378Oaklander 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.
- Background: PubMed 20879972Lefrandt 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.
- Background: PubMed 18220622Kles 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.
- Background: PubMed 31344333Impellizzeri 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.
- Background: PubMed 25164769Impellizzeri 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.
- Background: PubMed 15536624England 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.
- Background: PubMed 30121836Bartolucci 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.
- Individual participant dataSharing planned: 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
andrea truini, full professor principal investigator
department of human neuroscience, sapienza university
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing 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 in people with Diabete Type 2, run by University of Roma La Sapienza at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 8 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact andrea truini, Full Professor (+39649914122, andrea.truini@uniroma1.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in average daily pain intensity (time frame: Time Frame: Baseline to Week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07689214, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jul 2026.