Diabetic NeuropathiesNCT05422352
Role of Carnosine in Combination With Vitamin B Complex in Preventing the Progression of Diabetic Neuropathy in Type 2 Diabetes Patients
A study testing Carnosine in people with Diabetic Neuropathies, run by Beni-Suef University at 1 site in Egypt.
Trial summary
Evaluation of the influence of oral administration of carnosine in combination with vitamin B Complex in preventing the progression of diabetic neuropathy in type 2 diabetes patients. Read more about this study
- Who is it for?
- Ages 20 to 100 years
- Conditions the study is for
- Diabetic Neuropathies
- What is being tested?
- Carnosine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteEgypt
- Study dates
- 14 Jan 2021to 28 Mar 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 20 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Type 2 diabetes Patients as per ADA criteria.
- Patients were showing clinical signs of Diabetic neuropathy verified by a neurologist and confirmed by a score ≥7 on the MNSI questionnaire (Michigan Neuropathy Screening Instrument), with abnormal nerve conduction measurement.
- Patients on a regular visit to the clinic.
Who cannot join
- Patients with neuropathy of non-diabetic origin were excluded.
- Patients with a BMI of 40 kg/m2 or more and those pregnant or breastfeeding were also excluded
Trial locations and contacts
1 site in 1 country.
Egypt1 site
Beni Suef University faculty of pharmacy
Banī Suwayf, Beni Suweif Governorate, 62511
About this study
Evaluation of the influence of oral administration of carnosine in combination with vitamin B Complex in preventing the progression of diabetic neuropathy in type 2 diabetes patients.
Read the detailed description
Diabetic peripheral neuropathy (DPN) is considered the most common chronic complication of diabetes mellitus, with an incidence rate of about 50%.
DPN is a group of clinical syndromes that affects single or combined regions in the nervous system and is considered one of the microvascular complications that affect greatly the quality of life of patients due to pain and frequency of hospitalization.
DPN commonly develops silent without symptoms in the early stages and when symptoms start appearing only a few effective therapies are available and that is what causes significant patient suffering and societal burden.
Those mechanisms of pain and treatment remain challenging and are restricted by variable efficacy and side effects of therapies and intensification of glycemic control remain the cornerstone for the prevention or delay of DPN.
Lately, it has been proven that long-term low-grade inflammation has an important role in DPN pathogenesis. Clinical trials in DPN patients with pain and without pain showed that the DPN with pain group had higher inflammation markers.
In addition, DPN patients with pain had more increased cytokine levels compared with DPN patients without pain. Besides the correlation between abnormalities in nerve fibers and the rise in interleukin (IL)-6 and IL-10.
Moreover, Oxidative stress plays an important role in the development of diabetic neuropathy a reactive oxygen species (ROS) increases the progression of nerve fiber damage and dysfunction.
Those reactive oxygen species are capable of destroying the lipids found in the myelinated structures of nerves resulting in axon loss and disturbance in the microvasculature of the peripheral nervous system.
Antioxidants are available endogenously as a normal defense mechanism of the cell or obtained exogenously from diet and could play an important role in the progression of damage to the neurons in Diabetic neuropathy.
Carnosine, a naturally-occurring dipeptide (β-alanyl-L-histidine) first described in 1900 by Gulewitsch and Amiradzibi, is found predominantly in post-mitotic tissues (e.g. brain and innervated muscle) of vertebrates.
Carnosine is claimed to decrease oxygen-free-radical mediated damage to cellular macromolecules either by chelating divalent cations or scavenging hydroxy radicals with its imidazole moiety. Free-radical damage is not the only process to affects the structure of proteins and nucleic acids.
Furthermore, previous studies proved the neuroprotective action of carnosine with its anti-inflammatory and antioxidant properties.
Moreover, another study highlighted the use of carnosine as a supportive treatment against neurotoxins.
Also, Carnosine has been shown to protect cultured neurons from oxygen-glucose deprivation and to exhibit neuroprotective properties in animal models of global and cerebral ischemia
- Conditions
- Diabetic Neuropathies
- Being tested
- Carnosine
- Keywords
- Carnosine, diabetic neuropathy, oxidative stress, inflammation, Nerve conduction, type 2 diabetes, hyperglycemia, neopterin, nerve growth factor
- Medical subject headings
- Diabetic Neuropathies, Inflammation, Diabetes Mellitus, Type 2, Hyperglycemia, Hereditary Sensory and Autonomic Neuropathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CarnosineDietary supplement
Patients who will receive carnosine supplementation 500mg capsules (Now foods) in combination with Vitamin B complex (B1+B6+B12, 150 mg+100 mg+1 mg, respectively, Neurovit, European Egyptian Pharm. Ind., Egypt), two tablets per day
| Study group | Role | What they receive |
|---|---|---|
| intervention Group | Experimental | Patients who will receive carnosine supplementation + Vitamin B complex two tablets per day Receives: Dietary Supplement: Carnosine |
| Control group | No intervention | Patients will receive only Vitamin B Complex two tablets per day |
What is being measured
The primary outcome is the main question the study is designed to answer.
Neopterin biomarker
Neopterin, a marker of inflammation and cellular immune response, is elevated in conditions of T-cell or macrophages activation. Diabetic peripheral neuropathy (DPN) is associated with inflammatory/immune processes therefore Investigators hypothesized that it will decrease after intervention
Measured: 3 months
malondialdehyde biomarker
it is oxidative stress marker that increases in the lipid peroxidation and inflammation happening during diabetic neuropathy and investigators hypothesized that it will decrease after intervention
Measured: 3 months
Nerve Growth Factor
a neurotrophic factor and neuropeptide primarily involved in the regulation of growth, maintenance, proliferation, and survival of certain target neurons and investigathypothesized its increase after intervention
Measured: 3 months
Nerve Growth Factor
a neurotrophic factor and neuropeptide primarily involved in the regulation of growth, maintenance, proliferation, and survival of certain target neurons and investigators hypothesized its increase after intervention
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2022
- Study start14 Jan 2021
- Primary completion30 Jan 2022
- Study completion28 Mar 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Diabetic NeuropathiesStudies of the same condition, open and under way.
- More trials run by Beni-Suef UniversityThe 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- intervention study clinical trial
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Beni-Suef University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mahitab Hany Ahmed, Beni-Suef University
- Investigators
- H F Salem, Professor, Study chair, Beni-Suef University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05422352
- Sponsor's protocol ID
- Carnosine Diabetic neuropathy
- Status last verified
- Jun 2022
- First submitted
- 14 Jun 2022
- Last updated
- 29 Jun 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Hipkiss AR. Glycation, ageing and carnosine: are carnivorous diets beneficial? Mech Ageing Dev. 2005 Oct;126(10):1034-9. doi: 10.1016/j.mad.2005.05.002.
PubMed 15955546Oyenihi AB, Ayeleso AO, Mukwevho E, Masola B. Antioxidant strategies in the management of diabetic neuropathy. Biomed Res Int. 2015;2015:515042. doi: 10.1155/2015/515042. Epub 2015 Mar 2.
PubMed 25821809Edwards JL, Vincent AM, Cheng HT, Feldman EL. Diabetic neuropathy: mechanisms to management. Pharmacol Ther. 2008 Oct;120(1):1-34. doi: 10.1016/j.pharmthera.2008.05.005. Epub 2008 Jun 13.
PubMed 18616962Tesfaye S, Selvarajah D. Advances in the epidemiology, pathogenesis and management of diabetic peripheral neuropathy. Diabetes Metab Res Rev. 2012 Feb;28 Suppl 1:8-14. doi: 10.1002/dmrr.2239.
PubMed 22271716Vinik A I, "Diabetic Neuropathies," Contemp. Endocrinol. Controv. Treat. Diabetes Clin. Res. Asp.(2000), 109-134.
Callaghan BC, Cheng HT, Stables CL, Smith AL, Feldman EL. Diabetic neuropathy: clinical manifestations and current treatments. Lancet Neurol. 2012 Jun;11(6):521-34. doi: 10.1016/S1474-4422(12)70065-0. Epub 2012 May 16.
PubMed 22608666Shakher J, Stevens MJ. Update on the management of diabetic polyneuropathies. Diabetes Metab Syndr Obes. 2011;4:289-305. doi: 10.2147/DMSO.S11324. Epub 2011 Jul 21.
PubMed 21887102Jin HY, Park TS. Role of inflammatory biomarkers in diabetic peripheral neuropathy. J Diabetes Investig. 2018 Sep;9(5):1016-1018. doi: 10.1111/jdi.12794. Epub 2018 Jan 22.
PubMed 29277966Doupis J, Lyons TE, Wu S, Gnardellis C, Dinh T, Veves A. Microvascular reactivity and inflammatory cytokines in painful and painless peripheral diabetic neuropathy. J Clin Endocrinol Metab. 2009 Jun;94(6):2157-63. doi: 10.1210/jc.2008-2385. Epub 2009 Mar 10.
PubMed 19276232Hipkiss AR, Michaelis J, Syrris P. Non-enzymatic glycosylation of the dipeptide L-carnosine, a potential anti-protein-cross-linking agent. FEBS Lett. 1995 Aug 28;371(1):81-5. doi: 10.1016/0014-5793(95)00849-5.
PubMed 7664889Tsai SJ, Kuo WW, Liu WH, Yin MC. Antioxidative and anti-inflammatory protection from carnosine in the striatum of MPTP-treated mice. J Agric Food Chem. 2010 Nov 10;58(21):11510-6. doi: 10.1021/jf103258p. Epub 2010 Oct 6.
PubMed 20925384
Study at a glance
From the registry record, last updated by the sponsor on 29 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of Carnosine in Combination With Vitamin B Complex in Preventing the Progression of Diabetic Neuropathy in Type 2 Diabetes Patients
- ClinicalTrials.gov ID
- NCT05422352
- Acronym / sponsor ID
- Carnosine Diabetic neuropathy
- Conditions
- Diabetic Neuropathies
- Keywords
- Carnosine, diabetic neuropathy, oxidative stress, inflammation, Nerve conduction, type 2 diabetes, hyperglycemia, neopterin
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Beni-Suef UniversityUniversity, hospital or other
- Study start
- 14 Jan 2021 (actual)
- Primary completion
- 30 Jan 2022 (actual)
- Study completion
- 28 Mar 2022 (actual)
- First posted
- 16 Jun 2022 (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.
Evaluation of the influence of oral administration of carnosine in combination with vitamin B Complex in preventing the progression of diabetic neuropathy in type 2 diabetes patients.
Detailed description
Diabetic peripheral neuropathy (DPN) is considered the most common chronic complication of diabetes mellitus, with an incidence rate of about 50%.
DPN is a group of clinical syndromes that affects single or combined regions in the nervous system and is considered one of the microvascular complications that affect greatly the quality of life of patients due to pain and frequency of hospitalization.
DPN commonly develops silent without symptoms in the early stages and when symptoms start appearing only a few effective therapies are available and that is what causes significant patient suffering and societal burden.
Those mechanisms of pain and treatment remain challenging and are restricted by variable efficacy and side effects of therapies and intensification of glycemic control remain the cornerstone for the prevention or delay of DPN.
Lately, it has been proven that long-term low-grade inflammation has an important role in DPN pathogenesis. Clinical trials in DPN patients with pain and without pain showed that the DPN with pain group had higher inflammation markers.
In addition, DPN patients with pain had more increased cytokine levels compared with DPN patients without pain. Besides the correlation between abnormalities in nerve fibers and the rise in interleukin (IL)-6 and IL-10.
Moreover, Oxidative stress plays an important role in the development of diabetic neuropathy a reactive oxygen species (ROS) increases the progression of nerve fiber damage and dysfunction.
Those reactive oxygen species are capable of destroying the lipids found in the myelinated structures of nerves resulting in axon loss and disturbance in the microvasculature of the peripheral nervous system.
Antioxidants are available endogenously as a normal defense mechanism of the cell or obtained exogenously from diet and could play an important role in the progression of damage to the neurons in Diabetic neuropathy.
Carnosine, a naturally-occurring dipeptide (β-alanyl-L-histidine) first described in 1900 by Gulewitsch and Amiradzibi, is found predominantly in post-mitotic tissues (e.g. brain and innervated muscle) of vertebrates.
Carnosine is claimed to decrease oxygen-free-radical mediated damage to cellular macromolecules either by chelating divalent cations or scavenging hydroxy radicals with its imidazole moiety. Free-radical damage is not the only process to affects the structure of proteins and nucleic acids.
Furthermore, previous studies proved the neuroprotective action of carnosine with its anti-inflammatory and antioxidant properties.
Moreover, another study highlighted the use of carnosine as a supportive treatment against neurotoxins.
Also, Carnosine has been shown to protect cultured neurons from oxygen-glucose deprivation and to exhibit neuroprotective properties in animal models of global and cerebral ischemia
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- intervention study clinical trial
| Arm | Type | Receives |
|---|---|---|
| intervention Group | Experimental | Dietary Supplement: CarnosinePatients who will receive carnosine supplementation + Vitamin B complex two tablets per day |
| Control group | No intervention | –Patients will receive only Vitamin B Complex two tablets per day |
Who may qualify
- Ages
- 20 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Type 2 diabetes Patients as per ADA criteria.
- Patients were showing clinical signs of Diabetic neuropathy verified by a neurologist and confirmed by a score ≥7 on the MNSI questionnaire (Michigan Neuropathy Screening Instrument), with abnormal nerve conduction measurement.
- Patients on a regular visit to the clinic.
Key exclusion criteria (2 listed)
- Patients with neuropathy of non-diabetic origin were excluded.
- Patients with a BMI of 40 kg/m2 or more and those pregnant or breastfeeding were also excluded
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 |
|---|---|---|
| CarnosinePatients who will receive carnosine supplementation 500mg capsules (Now foods) in combination with Vitamin B complex (B1+B6+B12, 150 mg+100 mg+1 mg, respectively, Neurovit, European Egyptian Pharm. Ind., Egypt), two tablets per day | Dietary supplement | intervention Group |
Primary outcome
Neopterin biomarker
Time frame: 3 months
Neopterin, a marker of inflammation and cellular immune response, is elevated in conditions of T-cell or macrophages activation. Diabetic peripheral neuropathy (DPN) is associated with inflammatory/immune processes therefore Investigators hypothesized that it will decrease after intervention
malondialdehyde biomarker
Time frame: 3 months
it is oxidative stress marker that increases in the lipid peroxidation and inflammation happening during diabetic neuropathy and investigators hypothesized that it will decrease after intervention
Nerve Growth Factor
Time frame: 3 months
a neurotrophic factor and neuropeptide primarily involved in the regulation of growth, maintenance, proliferation, and survival of certain target neurons and investigathypothesized its increase after intervention
Nerve Growth Factor
Time frame: 3 months
a neurotrophic factor and neuropeptide primarily involved in the regulation of growth, maintenance, proliferation, and survival of certain target neurons and investigators hypothesized its increase after intervention
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jun 2022.
- Background: PubMed 15955546Hipkiss AR. Glycation, ageing and carnosine: are carnivorous diets beneficial? Mech Ageing Dev. 2005 Oct;126(10):1034-9. doi: 10.1016/j.mad.2005.05.002.
- Results publication: PubMed 25821809Oyenihi AB, Ayeleso AO, Mukwevho E, Masola B. Antioxidant strategies in the management of diabetic neuropathy. Biomed Res Int. 2015;2015:515042. doi: 10.1155/2015/515042. Epub 2015 Mar 2.
- Results publication: PubMed 18616962Edwards JL, Vincent AM, Cheng HT, Feldman EL. Diabetic neuropathy: mechanisms to management. Pharmacol Ther. 2008 Oct;120(1):1-34. doi: 10.1016/j.pharmthera.2008.05.005. Epub 2008 Jun 13.
- Results publication: PubMed 22271716Tesfaye S, Selvarajah D. Advances in the epidemiology, pathogenesis and management of diabetic peripheral neuropathy. Diabetes Metab Res Rev. 2012 Feb;28 Suppl 1:8-14. doi: 10.1002/dmrr.2239.
- Results publicationVinik A I, "Diabetic Neuropathies," Contemp. Endocrinol. Controv. Treat. Diabetes Clin. Res. Asp.(2000), 109-134.
- Results publication: PubMed 22608666Callaghan BC, Cheng HT, Stables CL, Smith AL, Feldman EL. Diabetic neuropathy: clinical manifestations and current treatments. Lancet Neurol. 2012 Jun;11(6):521-34. doi: 10.1016/S1474-4422(12)70065-0. Epub 2012 May 16.
- Results publication: PubMed 21887102Shakher J, Stevens MJ. Update on the management of diabetic polyneuropathies. Diabetes Metab Syndr Obes. 2011;4:289-305. doi: 10.2147/DMSO.S11324. Epub 2011 Jul 21.
- Results publication: PubMed 29277966Jin HY, Park TS. Role of inflammatory biomarkers in diabetic peripheral neuropathy. J Diabetes Investig. 2018 Sep;9(5):1016-1018. doi: 10.1111/jdi.12794. Epub 2018 Jan 22.
- Results publication: PubMed 19276232Doupis J, Lyons TE, Wu S, Gnardellis C, Dinh T, Veves A. Microvascular reactivity and inflammatory cytokines in painful and painless peripheral diabetic neuropathy. J Clin Endocrinol Metab. 2009 Jun;94(6):2157-63. doi: 10.1210/jc.2008-2385. Epub 2009 Mar 10.
- Results publication: PubMed 7664889Hipkiss AR, Michaelis J, Syrris P. Non-enzymatic glycosylation of the dipeptide L-carnosine, a potential anti-protein-cross-linking agent. FEBS Lett. 1995 Aug 28;371(1):81-5. doi: 10.1016/0014-5793(95)00849-5.
- Results publication: PubMed 20925384Tsai SJ, Kuo WW, Liu WH, Yin MC. Antioxidative and anti-inflammatory protection from carnosine in the striatum of MPTP-treated mice. J Agric Food Chem. 2010 Nov 10;58(21):11510-6. doi: 10.1021/jf103258p. Epub 2010 Oct 6.
- Individual participant dataSharing planned: No
Related trials for Diabetic Neuropathies
Recruiting
PAW-Hydrogel for Chronic Wound Healing
Diabetic Foot Ulcer (DFU), Pressure Ulcer (PU)
Active, not recruiting
Wearable Insoles for Recurrent Diabetic Ulcer Prevention
Diabetes, Peripheral Neuropathy
Recruiting
Effect of 4-7-8 Breathing Technique on Pain and Anxiety During Electromyography in Diabetic Neuropathy
Diabetic Neuropathies, Diabetes Mellitus (Type 2)
Active, not recruiting
Evaluation of Personalized Nutritional Intervention on Wound Healing of Cutaneous Ulcers in Diabetics
Foot, Diabetic
Active, not recruiting
Comparative Effects Of Sensory Reweighting And Proprioceptive Facilitation Training On Balance And Fall Risk In Diabetic Peripheral Neuropathy
Diabetic Peripheral Neuropathy (DPN)
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. This study is not recruiting at the moment.
H F Salem, Professor study chair
Beni-Suef 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 Carnosine in people with Diabetic Neuropathies, run by Beni-Suef University at 1 site in Egypt.
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 3 inclusion and 2 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: finished, as of the sponsor's last update on 29 Jun 2022. 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 Egypt. 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. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Neopterin biomarker (time frame: 3 months). The study lists 4 primary outcomes in all. 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 NCT05422352, which also lists 11 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 29 Jun 2022.