Clinical Outcome of Vinpocetine in Diabetic Nephropathy

The Effect of Vinpocetine on the Clinical Outcome of Patients With Diabetic Nephropathy

The goal of this controlled, randomized, clinical trial is to evaluate the effect of vinpocetine on clinical outcomes on the diabetic nephropathy patients.

The following will be evaluated; anthropometrics, kidney functions, glucose panel, lipid panel, ICAM-1, quality of life.

Participants will receive either vinpocetine or placebo, twice daily for 3 months.

Study Overview

• Status: Recruiting
• Conditions: Diabetic Kidney Disease; Diabetic Nephropathies
• Intervention / Treatment: Drug: Vinpocetine; Drug: Standard Therapy; Other: Placebo

Detailed Description

Diabetes mellitus affects around 537 million people globally, projected to reach over 700 million by 2045. Egypt is notably impacted, ranking tenth in prevalence and contributing significantly to chronic kidney disease, blindness, and stroke. Diabetic nephropathy (DN) arises as a severe complication, affecting about 50% of type 2 diabetes patients and leading to end-stage kidney disease. Its pathogenesis involves complex mechanisms like persistent hyperglycemia, inflammation, oxidative stress, and endothelial dysfunction, culminating in kidney damage and subsequently fibrosis.

Current treatments focus on managing blood glucose, pressure, and lipid levels, often using drugs that target the renin-angiotensin-aldosterone system. However, these therapies aren't always sufficient to prevent progression to end-stage renal disease. Therefore, exploring new approaches is crucial.

Vinpocetine, a derivative of Vinca minor leaves, is a selective inhibitor of phosphodiesterase type 1 (PDE1). It has noteworthy antioxidant, anti-inflammatory, and anti-apoptotic properties.

Clinical and experimental studies suggest its potential in various conditions, including neurodegenerative disorders, cardiovascular diseases, and inflammation-related ailments. Notably, it has shown promising effects in improving endothelial function and reducing inflammatory markers like TNF-α and IL-6.

In kidney injury models, Vinpocetine has demonstrated nephroprotective effects, improving kidney function markers, reducing albumin excretion, and decreasing renal hypertrophy. It can also exert its antioxidant effects through the restoration of the depleted GSH content, and the attenuation of the increase in MDA levels. In a clinical trial investigating the effect of vinpocetine in acute ischemic stroke patients, vinpocetine inhibited the upregulation of TNF-α, IL-6, MCP-1, ICAM-1, VCAM-1, as well as CRP in blood plasma. It also appears to impact atherosclerosis by positively affecting lipid profiles and reducing atherosclerosis lesion formation through mechanisms like inhibition of NF-κB and modulation of ox-LDL receptors.

Based on vinpocetine's promising profile and minimal reported side effects, this work aims to investigate the Vinpocetine's potential in treating diabetic nephropathy and associated complications.

• Study Type: Interventional
• Enrollment (Estimated): 64
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Tamer El Said; Phone Number: 201227366062; Email: drtamer_elsaid@med.asu.edu.eg

Study Locations

• Egypt
  • Abbasseia
    • Cairo, Abbasseia, Egypt, 11588
      • Not yet recruiting
      • Ain Shams University Hospital
      • Contact: Tamer El Said; Phone Number: 01227366062; Email: drtamer_elsaid@med.asu.edu.eg
  • Abbasseya
    • Cairo, Abbasseya, Egypt, 11588
      • Recruiting
      • Ain shams hospitals
      • Contact: Tamer El Said; Phone Number: 01227366062

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years,
• Type II diabetic patients with CKD stage 3 (eGFR = 30 - 59 ml/min) or stage 4 (eGFR 15-29 ml/min),
• Albumin/Creatinine ratio (ACR): 30 - 300 μg /mg (microalbuminuria),
• Stable standard therapy for at least three months prior to inclusion in the study.

Exclusion Criteria:

• Kidney donor or recipient,
• Active malignancy,
• Pregnancy or breastfeeding,
• Known intolerance or hypersensitivity to VPN,
• Participation in other interventional trials,
• Patients with inadequate liver function (ALT and AST three times greater than the upper normal limits),
• Patients with severe comorbidities
• Patients receiving warfarin

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vinpocetine + Standard Therapy; Vinpocetine capsules, 30 mg, twice daily, with meals for 3 months	Drug: Vinpocetine; Vinca derivative of apovincamine, phosphodiestrase 1 inhibitor, sodium-gated voltage channel; Drug: Standard Therapy; Anti-hypertensive and anti-diabetic medications according to the the institution's protocol
Placebo Comparator: Placebo + Standard Therapy; Placebo, twice daily, with meals for 3 months	Drug: Standard Therapy; Anti-hypertensive and anti-diabetic medications according to the the institution's protocol; Other: Placebo; Starch-filled capsules, matching those of the intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
level of Albuminuria	assessment of the amount of albumin excreted in urine	Samples will be measured at baseline and after 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Albumin: creatinine ratio (ACR)	The urine ACR is calculated by dividing the urine albumin concentration by the urine creatinine concentration to account for differences in urine volume and more closely approximate the gold standard, 24-hour urine albumin excretion.	Samples will be measured at baseline and after 12 weeks
Serum Creatinine	assessment of the serum level of creatinine	Samples will be measured at baseline and after 12 weeks
Blood urea nitrogen	assessment of the level of blood urea nitrogen in serum	Samples will be measured at baseline and after 12 weeks
Hemoglobin A1c	assessment of the level of glycated hemoglobin	Samples will be measured at baseline and after 12 weeks
Fasting and postprandial blood glucose	Evaluation of blood level glucose after 8-hrs fasting and 2-hrs postprandial	Samples will be measured at baseline and after 12 weeks
Lipid panel	Serum Low-density Lipoprotein Cholesterol (LDL-C), High-density Lipoprotein Cholesterol (HDL-C), Total Cholesterol, Triglycerides	Samples will be measured at baseline and after 12 weeks
Body Mass index (BMI)	The BMI will be calculated using the following formula BMI=Weight(kg)/ height(m)^2	Samples will be measured at baseline and after 12 weeks
Assessment of endothelial functions	Serum ICAM-1 using ELISA	Samples will be measured at baseline and after 12 weeks
Quality of life (QoL) Assessment	Quality of Life (QoL) assessment using Diabetes-39 (D-39) Questionnaire. The D-39 questionnaire is a multi-dimensional, self-administrating, diabetes-specific scale. It consists of 39 items in five domains, namely energy, and mobility (15 items), diabetes control (12 items), anxiety and worry (4 items), social and peer burden (5 items), and sexual functioning (3 items). Scores are marked on a seven-point scale ranging from 1 (not affected at all) to 7 (extremely affected). The raw score resulting from the summation of each dimension will then be transformed linearly to 0 to 100 scales, using the following formula: (Raw score - minimum value)/(maximum value - minimum value) × 100 A score of 0 indicates the least impact on QoL, and a score of 100 indicates the maximum impact on QoL	Samples will be measured at baseline and after 12 weeks

Collaborators and Investigators

• Sponsor: Ain Shams University

Study record dates

Study Major Dates

• Study Start (Actual): July 10, 2024
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: May 27, 2024
• First Submitted That Met QC Criteria: June 1, 2024
• First Posted (Actual): June 4, 2024

Study Record Updates

• Last Update Posted (Actual): July 11, 2024
• Last Update Submitted That Met QC Criteria: July 10, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: diabetic kidney disease; Diabetic nephropathy; UACR; ICAM; Vinpocetine
• Additional Relevant MeSH Terms: Urologic Diseases; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Diabetic Nephropathies; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Neuroprotective Agents; Protective Agents; Phosphodiesterase Inhibitors; Nootropic Agents; Vinpocetine
• Other Study ID Numbers: 238

Drug and device information, study documents

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