Role of Carnosine in Combination With Vitamin B Complex in Preventing the Progression of Diabetic Neuropathy in Type 2 Diabetes Patients

Diabetic Neuropathies Clinical Trial

Official title:

Role of Carnosine in Combination With Vitamin B Complex in Preventing the Progression of Diabetic Neuropathy in Type 2 Diabetes Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05422352
• Other study ID #: Carnosine Diabetic neuropathy
• Status: Completed
• Phase: N/A
• Start date: January 14, 2021
• Est. completion date: March 28, 2022

Study information

• Verified date: June 2022
• Source: Beni-Suef University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: March 28, 2022
• Est. primary completion date: January 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 100 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Diabetic Neuropathies
• Peripheral Nervous System Diseases

Intervention

Dietary Supplement:
• Carnosine
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

Locations

Country	Name	City	State
Egypt	Beni Suef University faculty of pharmacy	Bani Suwayf	Bani Suwayf

Sponsors (1)

Lead Sponsor	Collaborator
Beni-Suef University

Country where clinical trial is conducted

Egypt, 

References & Publications (11)

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. Review. — View Citation

Doupis 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 — View Citation

Edwards 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. Review. — View Citation

Hipkiss 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. — View Citation

Hipkiss AR. Glycation, ageing and carnosine: are carnivorous diets beneficial? Mech Ageing Dev. 2005 Oct;126(10):1034-9. Review. — View Citation

Jin 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. Review. — View Citation

Oyenihi 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. Review. — View Citation

Shakher 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. — View Citation

Tesfaye 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. Review. — View Citation

Tsai 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. — View Citation

Vinik A I, "Diabetic Neuropathies," Contemp. Endocrinol. Controv. Treat. Diabetes Clin. Res. Asp.(2000), 109-134.

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	3 months
Primary	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	3 months
Primary	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	3 months
Primary	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	3 months