Assessment of Antioxidant Therapy on Oxidative Stress Biomarkers in Type 2 Diabetic Patients With Neuropathy

Peripheral Diabetic Neuropathy Clinical Trial

— RCT  

Official title:

Assessment of Resveratrol, Alpha Lipoic Acid and Superoxide Dismutase on Oxidative Stress Biomarkers in Type 2 Diabetes Mellitus Patients With Neuropathy: A Randomized Control Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT06131918
• Other study ID #: HAMIDHABIB
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: January 9, 2023
• Est. completion date: February 20, 2024

Study information

• Verified date: November 2023
• Source: Khyber Medical University Peshawar
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Type 2 DM subjects having numbness, tingling and paresthesia in hands and feet (neuropathy) will be recruited. Screening of neuropathy will be done by Michigan screening instrument. This will be followed by nerve conduction studies. Specific blood parameters will also be checked. The subjects will then be divided into four treatment arms. Three groups will receive single drug and the fourth one will receive all the three drugs. These will be given for four months. Follow up will be done every month. At the end of four months, they will be assessed for any improvement in neuropathy by using Michigan neuropathy instrument and nerve conduction studies. Blood parameters will also be measured again.

Description:

Type 2 DM subjects having numbness, tingling and paresthesia in hands and feet (neuropathy) will be recruited. They will be screened by Michigan neuropathy scale. This is tool used for screening neuropathy. Subjects having a score equal to or greater then 4 will be examined for further evaluation. This will be followed by nerve conduction studies for objective assessment of neuropathy. For inclusion criteria the test performed will be HbA1c, CBC, ESR, RFTs and LFTs. After screening the baseline levels of Superoxide radical, Super oxide dismutase, Glutathione peroxidase and Malonaldehyde will be measured. The subjects will be randomly divided into four treatment arms. Group A will receive Triple regime antioxidant therapy including Resveratrol 1500 mg two times a day, Alpha lipoic acid 600 mg two times a day and Superoxide dismutase 250 mg once a day. Group B will receive Resveratrol 1500mg BD, Group C will be on Tab Alpha lipoic acid 600 mg BD and Group D will take Superoxide dismutase once a day. The subjects will be kept blinded about the medication. They will be followed every month in which their quality of life will be assessed using Nottingham health profile and neuropathy will be assessed by Michigan neuropathy scale. At the end of four months blood tests will again be performed to check the levels of Superoxide radical, Superoxide dismutase, Glutathione peroxidase and Malonaldehyde. NCS will be done to see any improvement in neuropathy.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 100
• Est. completion date: February 20, 2024
• Est. primary completion date: December 22, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 60 Years

Eligibility

Inclusion Criteria:

• Patients with Type 2 Diabetes Mellitus
• Age between 40-60 years

Exclusion Criteria:

• Malignancy
• Vitamin B12 deficiency
• History of drug or alcohol abuse
• Taking antioxidant treatment
• History and baseline investigations for renal hepatic and haematological diseases
• Pregnant or lactating women.

Related Conditions & MeSH terms

• Diabetic Neuropathies
• Peripheral Diabetic Neuropathy
• Peripheral Nervous System Diseases

Intervention

Drug:
• Resveratrol, Alpha lipoic acid, Super oxide dismutase
Tab Resveratrol 1500 mg BD Tab Alpha lipoic Acid 600 mg BD Tab Superoxide dismutase 250 mg BD
• Resveratrol
Tab Resveratrol 1500 mg BD
• Alpha lipoic acid
Tab Alpha lipoic acid 600 mg BD
• Super Oxide Dismutase
Tab Super oxide dismutase 250 mg BD

Locations

Country	Name	City	State
Pakistan	Syed Hamid Habib	Peshawar	KPK

Sponsors (1)

Lead Sponsor	Collaborator
Khyber Medical University Peshawar

Country where clinical trial is conducted

Pakistan, 

References & Publications (12)

Bhatt JK, Thomas S, Nanjan MJ. Resveratrol supplementation improves glycemic control in type 2 diabetes mellitus. Nutr Res. 2012 Jul;32(7):537-41. doi: 10.1016/j.nutres.2012.06.003. Epub 2012 Jul 27. — View Citation

Bjornholm M, Zierath JR. Insulin signal transduction in human skeletal muscle: identifying the defects in Type II diabetes. Biochem Soc Trans. 2005 Apr;33(Pt 2):354-7. doi: 10.1042/BST0330354. — View Citation

Jiang B, Guo L, Li BY, Zhen JH, Song J, Peng T, Yang XD, Hu Z, Gao HQ. Resveratrol attenuates early diabetic nephropathy by down-regulating glutathione s-transferases Mu in diabetic rats. J Med Food. 2013 Jun;16(6):481-6. doi: 10.1089/jmf.2012.2686. — View Citation

Kennedy DO, Wightman EL, Reay JL, Lietz G, Okello EJ, Wilde A, Haskell CF. Effects of resveratrol on cerebral blood flow variables and cognitive performance in humans: a double-blind, placebo-controlled, crossover investigation. Am J Clin Nutr. 2010 Jun;91(6):1590-7. doi: 10.3945/ajcn.2009.28641. Epub 2010 Mar 31. — View Citation

Kumar A, Kaundal RK, Iyer S, Sharma SS. Effects of resveratrol on nerve functions, oxidative stress and DNA fragmentation in experimental diabetic neuropathy. Life Sci. 2007 Mar 6;80(13):1236-44. doi: 10.1016/j.lfs.2006.12.036. Epub 2007 Jan 20. — 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. — View Citation

Pham-Huy LA, He H, Pham-Huy C. Free radicals, antioxidants in disease and health. Int J Biomed Sci. 2008 Jun;4(2):89-96. — View Citation

Rahimi-Madiseh M, Malekpour-Tehrani A, Bahmani M, Rafieian-Kopaei M. The research and development on the antioxidants in prevention of diabetic complications. Asian Pac J Trop Med. 2016 Sep;9(9):825-831. doi: 10.1016/j.apjtm.2016.07.001. Epub 2016 Aug 5. — View Citation

Szkudelski T, Szkudelska K. Resveratrol and diabetes: from animal to human studies. Biochim Biophys Acta. 2015 Jun;1852(6):1145-54. doi: 10.1016/j.bbadis.2014.10.013. Epub 2014 Oct 27. — View Citation

Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol. 2007;39(1):44-84. doi: 10.1016/j.biocel.2006.07.001. Epub 2006 Aug 4. — View Citation

Villegas-Rivera G, Roman-Pintos LM, Cardona-Munoz EG, Arias-Carvajal O, Rodriguez-Carrizalez AD, Troyo-Sanroman R, Pacheco-Moises FP, Moreno-Ulloa A, Miranda-Diaz AG. Effects of Ezetimibe/Simvastatin and Rosuvastatin on Oxidative Stress in Diabetic Neuropathy: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Oxid Med Cell Longev. 2015;2015:756294. doi: 10.1155/2015/756294. Epub 2015 Jul 28. — View Citation

Xiao WH, Bennett GJ. Effects of mitochondrial poisons on the neuropathic pain produced by the chemotherapeutic agents, paclitaxel and oxaliplatin. Pain. 2012 Mar;153(3):704-709. doi: 10.1016/j.pain.2011.12.011. Epub 2012 Jan 13. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Subjective improvement in Diabetic Neuropathy	Subjective improvement in Diabetic neuropathy will be assessed by Michigan Neuropathy Screening Instrument (MNSI). It consists of a patient version which is a questionnaire that will be filled by the patient. These questions will assess the symptoms of neuropathy on a scale of 0-13 points. A score of 4 or greater than 4 indicates neuropathy. It also consists of a physical assessment form which will be completed by the health professional. The physical assessment has a scoring of 0-10 points. In physical assessment appearance of the feet is checked for any deformity, dryness ulceration. Ankle reflex, vibration perception at great toe and monofilament test is also performed. Decrease in scoring will show improvement in neuropathy which means a score equal to or greater than 4 indicates neuropathy and less than 4 indicates no neuropathy or improvement in neuropathy.	four months
Primary	Objective improvement in Diabetic Neuropathy	Nerve conduction studies (NCS) which is the gold standard for diagnosis of neuropathy will be performed. Latency in (milliseconds), amplitude in (millivolts) and nerve conduction velocity in (meters/second) will be measured. Among sensory nerve median and ulnar in the hand will be examined and sural nerve in the foot. Among motor nerves in the hand median and ulnar will be examined and in the foot peroneal and tibial will be examined. A decrease in latency and an increase in amplitude and nerve conduction velocity will show improvement.	Four months
Secondary	levels of superoxide radical anion,	Change in the levels of superoxide radical anion	4 months
Secondary	Levels of Malonaldehyde oxidative stress biomarker	Change in the levels of oxidative stress biomarkers	Four months
Secondary	Levels of Superoxide dismutase and Glutathione peroxidase	Change in the levels of antioxidant enzymes	4 months