Effect of Resveratrol and Pharmacist Intervention on Diabetes Mellitus and Its Neuropathic Complication

Impact of Resveratrol and Pharmaceutical Care on Diabetes Mellitus and Its Neuropathic Complication

Management of symptoms associated with diabetic neuropathy is a difficult issue for clinicians since it usually does not respond to standard analgesics. Resveratrol is a naturally occurring plant-derived, polyphenolic compound, it exerts pleiotropic activity. The investigators believed that the implementation of multidisciplinary approaches including pharmacotherapy and provision of healthcare professional services such as pharmacist intervention are needed for alleviation of diabetic associated neuropathy.Therefore, the hypothesis of the present protocol is that the administration of resveratrol and/or provision of pharmaceutical care in patients with diabetic neuropathy might be of value in improving quality of life and managing diabetic neuropathic pain.The study is designed as a four-arm randomized, placebo-controlled clinical trial. Group one will be given only conventional hypoglycemic drugs. Group two patients will receive conventional hypoglycemic drugs accompanied by pharmacist interventions. Group three; patients will receive resveratrol 500 mg orally once daily after meals for three months, in addition to their regular hypoglycemic drugs. Group four; patients will receive resveratrol 500 mg orally once daily after meals along with their regular hypoglycemic drugs for a period of three months, accompanied by pharmacist interventions. Neuropathic pain will be measured by various neuropathic pain assessment tools. Nerve conduction studies will be performed to assess the effect of interventional therapy. The expected outcome will be the improvement of diabetic neuropathy associated symptoms along with glycemic status.

Study Overview

• Status: Completed
• Conditions: Diabetic Neuropathies
• Intervention / Treatment: Drug: Resveratrol; Drug: Placebo; Other: Resveratrol plus Pharmaceutical care; Other: Placebo+Pharmaceutical care

Detailed Description

• Diabetic neuropathy is the most common microvascular complication of diabetes, resulting from prolonged periods of hyperglycemia, damaging fragile nerve fibers and the walls of their blood vessels.
• Despite clinical developments in the treatment of diabetes complications, especially diabetic neuropathy, it still remains a clinical challenge with no effective solution.
• Conventional therapies such as anti-epileptics, opioid analgesics, and antidepressants for the treatment of neuropathic pain are quite challenging due to their serious adverse effects.
• There is a need to investigate novel effective and safe options.
• Recently, polyphenols have also been introduced as potential neuroprotective agents in diabetes.
• Alleviation of the symptoms associated with diabetic neuropathy and exerting preventive measures to halt the emergence of neuropathy complications are crucial priorities, and this requires multidisciplinary approaches including pharmacotherapy and provision of healthcare professional services such as pharmacist intervention.
• Aim of the study: to evaluate the effects of resveratrol and pharmaceutical care on the severity of diabetic neuropathy and improvement in the quality of life of diabetic patients.
• Study design: four-arm randomized, double-blind, placebo-controlled clinical trial.
• Interventions:Therapeutic intervention and Pharmacist intervention.
• Number of participants = 120
• Number of groups = 4 groups each of 30 patients

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Bushra Marouf, PhD; Phone Number: Dr. 009647701562796; Email: bushra.marouf@univsul.edu.iq
• Study Contact Backup: Name: Gulabakh Mohammed Amin, Bsc; Phone Number: 009647708914542; Email: gullabakh.mohammedamin@univsul.edu.iq

Study Locations

• Iraq
  • Sulaymānīyah, Iraq, 00964
    • College of Pharmacy-University of Sulaimani

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with pain due to bilateral peripheral neuropathy caused by type 2 diabetes mellitus.
• HbA1c of greater than 7%
• The daily pain must be present for at least 6 months, and the diagnosis will be confirmed by a score >4 on the Michigan Neuropathy Screening Instrument (MNSI), Douleur Neuropathique 4 (DN4). The severity of pain when evaluated for the past 24 was ≥4 on the 10 cm Visual Analogue Scale (VAS) at baseline without the use of analgesic for 48 hours.

Exclusion Criteria:

• Older subjects with high risks of cardiovascular diseases,
• Pregnant or breastfeeding,
• Having a prior renal transplant or current renal dialysis,
• Patients have a diagnosis of major depressive disorder, generalized anxiety disorder, heavy alcohol drinkers,
• Significant hepatic or renal disease,
• Patients on antioxidant therapy, or pentoxyphylline within the last month.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Resveratrol; Interventional group, participants in this group are receiving Resveratrol 500mg capsule once daily for 3 months.	Drug: Resveratrol; This group received resveratrol with the conventional therapy
Placebo Comparator: Placebo; Non-interventional group, participants are receiving only Placebo once daily for 3 months. Placebo formulated as capsule match the color and size of the active comparator,	Drug: Placebo; This group received placebo with the conventional therapy
Other: Resveratrol plus Pharmaceutical care; Interventional group, participants in this group are receiving Resveratrol 500mg capsule once daily for 3 months with pharmaceutical care.	Other: Resveratrol plus Pharmaceutical care; This group received Resveratrol with Pharmaceutical care in addition to the conventional therapy
Other: Placebo with pharmaceutical care; Interventional group, participants are receiving placebo along with pharmaceutical care for 3 months.	Other: Placebo+Pharmaceutical care; This group received placebo with Pharmaceutical care in addition to the conventional therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
visual analog scale (VAS)	to assess neuropathic pain, VAS scale ranges between 0-10 , 0 indicates no pain while 10 indicates severe pain.	up to 3 months
Douleur Neuropathique 4 questionnaire (DN4)	to assess the severity of diabetic peripheral neuropathy.	up to 3 months
The Michigan Neuropathy Screening Instrument (MNSI)	to assess the severity of diabetic peripheral neuropathy	up to 3 months
Electroneurography	Motor nerve conduction velocity (m/s), sensory nerve conduction velocity(m/s) will be measured using surface electrodes.	up to 3 months
Assessment of Quality of Life	using the RAND-36 health survey questionnaire	up to 3 months
Serum neopterin levels	biochemical marker for peripheral neuropathy	up to 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The mean change in fasting blood glucose	to assess glycemic status	up to 3 months
Mean change of glycated hemoglobin (HbA1c)-mmol/l	to assess glycemic status	up to 3 months
Measurement of serum level of LDL, cholesterol, HDL, Triglyceride	to assess the effect of the interventions on metabolic changes	up to 3 months

Collaborators and Investigators

• Sponsor: University of Sulaimani
• Investigators: Principal Investigator: Bushra Marouf, PhD, Department of Pharmacology and Toxicology-College of Pharmacy-University of Sulaimani

Publications and helpful links

General Publications

• Azmi S, ElHadd KT, Nelson A, Chapman A, Bowling FL, Perumbalath A, Lim J, Marshall A, Malik RA, Alam U. Pregabalin in the Management of Painful Diabetic Neuropathy: A Narrative Review. Diabetes Ther. 2019 Feb;10(1):35-56. doi: 10.1007/s13300-018-0550-x. Epub 2018 Dec 18.
• Collins C, Limone BL, Scholle JM, Coleman CI. Effect of pharmacist intervention on glycemic control in diabetes. Diabetes Res Clin Pract. 2011 May;92(2):145-52. doi: 10.1016/j.diabres.2010.09.023. Epub 2010 Oct 20.
• Elbarbary NS, Ismail EAR, El-Hilaly RA, Ahmed FS. Role of neopterin as a biochemical marker for peripheral neuropathy in pediatric patients with type 1 diabetes: Relation to nerve conduction studies. Int Immunopharmacol. 2018 Jun;59:68-75. doi: 10.1016/j.intimp.2018.03.026. Epub 2018 Apr 6.
• Naseri R, Farzaei F, Fakhri S, El-Senduny FF, Altouhamy M, Bahramsoltani R, Ebrahimi F, Rahimi R, Farzaei MH. Polyphenols for diabetes associated neuropathy: Pharmacological targets and clinical perspective. Daru. 2019 Dec;27(2):781-798. doi: 10.1007/s40199-019-00289-w. Epub 2019 Jul 27.
• Eid S, Sas KM, Abcouwer SF, Feldman EL, Gardner TW, Pennathur S, Fort PE. New insights into the mechanisms of diabetic complications: role of lipids and lipid metabolism. Diabetologia. 2019 Sep;62(9):1539-1549. doi: 10.1007/s00125-019-4959-1. Epub 2019 Jul 25.

Study record dates

Study Major Dates

• Study Start (Actual): December 5, 2021
• Primary Completion (Actual): December 1, 2022
• Study Completion (Actual): December 15, 2022

Study Registration Dates

• First Submitted: November 30, 2021
• First Submitted That Met QC Criteria: December 11, 2021
• First Posted (Actual): December 29, 2021

Study Record Updates

• Last Update Posted (Actual): March 14, 2023
• Last Update Submitted That Met QC Criteria: March 10, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Neuropathic pain; pharmaceutical care; Diabetic neuropathy; Resveratrol
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Nervous System Diseases; Endocrine System Diseases; Diabetes Complications; Neuromuscular Diseases; Peripheral Nervous System Diseases; Diabetes Mellitus; Diabetic Neuropathies; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Protective Agents; Antioxidants; Resveratrol
• Other Study ID Numbers: University of Sulaimani

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No