Effect of Obesity on Cyclosporine Blood Trough Level in Nephrotic Syndrome Patients

This study aims to assess the effect of obesity on therapeutic response and safety of cyclosporine trough level in nephrotic syndrome patients and calculating a suitable weight-based dose.

Study Overview

• Status: Recruiting
• Conditions: Nephrotic Syndrome
• Intervention / Treatment: Drug: Cyclosporine Capsule

Detailed Description

1. Ethical committee approval has been obtained from Ethics committee of Faculty of Medicine, Alexandria University.
2. Agreement from all participants should be taken in this clinical study by assigning an informed consent.
3. Nephrotic diseased patients,will be recruited from Alexandria main university hospital (AMUH).
4. The 74 participants will be non-randomly assigned into 2 groups.
5. The control group is non-obese nephrotic patients with BMI <25 kg/m2 will receive receive Cyclosporine capsule with conventional initial dose 3 mg/kg/day using actual weight.
6. The Case interventional group is Obese nephrotic patients with BMI> 25kg/m2 will receive Cyclosporine capsule with the best weight based dose to achieve the targeted therapeutic trough level and targeted urinary protein/ creatinine ratio.

7. All patients will be subjected to :

   • First visit: Full patient history, anthropometrics (weight, hight, BMI, fat %, water %, muscles% and clinical examination. Calculate the initial cyclosporine dose 3mg/kg/day in 2 divided doses based on actual weight.
   • Second visit after one month: blood sample withdrawal for measuring trough level, lipid profile and thyroid profile, urinary sample to measure uPCR If patients don't reach to targeted therapeutic trough level and targeted urinary protein/ creatinine ratio,re-modifying the dose and repeat the labs after another one month in third visit.
   • Finally find the best weight can be used to achieve the targeted therapeutic trough level and targeted urinary protein/ creatinine ratio, and its relation with fat content and lipid profile
8. The appropriate Statistical tests will be hold according to study design and parameters (parametric and non-parametric) to evaluate the significance of the results.
9. Results, conclusion, discussion and recommendations will be given.

• Study Type: Interventional
• Enrollment (Estimated): 74
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Enas A Mohamed, PharmD; Phone Number: +2 01004344021; Email: gs-enas.elkady@alexu.edu.eg
• Study Contact Backup: Name: Noha A Hamdy, PhD; Phone Number: +2 01005182151; Email: noha.alaaeldine@alexu.edu.eg

Study Locations

• Egypt
  • Alexandria, Egypt
    • Recruiting
    • Alexandria University
    • Principal Investigator: Noha A Hamdy, PhD
    • Contact: Noha A Hamdy, PhD; Phone Number: +2 01005182151; Email: noha.alaaeldine@alexu.edu.eg
    • Contact: Yasmin S Naga, PhD; Phone Number: +2 01222244673; Email: yasminenaga@gmail.com
    • Principal Investigator: Hanan M El-Goweilli, PhD
    • Principal Investigator: Yasmin S Naga, PhD
    • Principal Investigator: Enas A Mohamed, Pharm-D

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Obese and overweight Nephrotic syndrome adult patients receiving Cyclosporine for more than one month with prednisolone. (BMI>25 kg/m2)
• Normal or underweight individuals Nephrotic syndrome adult patients receiving Cyclosporine for more than one month with prednisolone. (serving as control group)

Exclusion Criteria:

• Hepatic patients liver cirrhosis (moderate to severe liver impairment)
• Cancer patients,
• Pregnant and lactating female patients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Obese nephrotic patients with BMI>25 kg/m2; Nephrotic obese patients receive Cyclosporine capsule initially according to weight-based dose then modifying the dose according to targeted therapeutic level. To determine the best weight can be used to get the targeted therapeutic level. Correlate with the lipid profile, fat percentage and other anthropometric measures.	Drug: Cyclosporine Capsule; Determination of the most appropriate weight based dose of Cyclosporine to achieve the target therapeutic drug level and response and its relation with fat percentage and lipid profile
Other: Non obese nephrotic patients with BMI<25 kg/m2; Nephrotic non-obese patients receive Cyclosporine capsule initially according to weight-based dose then modified dose according to targeted therapeutic level.	Drug: Cyclosporine Capsule; Determination of the most appropriate weight based dose of Cyclosporine to achieve the target therapeutic drug level and response and its relation with fat percentage and lipid profile

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cyclosporine level concentration and its correlation to anthropometric measures	Measuring of Cyclosporine level in whole blood after one month of starting the drug	1 month
Determine a suitable weight-based dose for obese patients	Modifying the Cyclosporine dose according to measured trough level	1 month
Measuring the weight as one of anthropometric measures	Measuring anthropometric measures as; weight in kilograms at base line of starting the Cyclosporine regimen.	Day 1
Measuring the height as one of anthropometric measures	Measuring anthropometric measures as;height in metres at base line of starting the Cyclosporine regimen.	Day 1
Measuring the BMI as one of anthropometric measures	Measuring anthropometric measures as; BMI (body mass index) in kilograms/meter^2 at base line of starting the Cyclosporine regimen.	Day 1
Measuring some of important in-body anthropometric measures	Measuring anthropometric measures as;body fat percentage, body water percentage and muscle percentage content at base line of starting the Cyclosporine regimen.	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of kidney functions	Measuring parameters represent the kidney functions including (serum creatinine in mg/dl.)	1 month
Assessment of kidney functions as clearance estimation	Measuring parameters represent the kidney functions including (estimated GFR in mL/min/1.73 m²)	1 month
Assessment of kidney functions as urinary protein release	Measuring parameters represent the kidney functions including (Urinary protein-creatinine ratio in gm/gm)	1 month
Lipid profile assessment	Measuring lipid profile including (HDL, LDL,VLDL and TG) in mg/dl.	1 month
Thyroid function assessment	Measuring Thyroid profile including (TSH, fT3, fT4 ).	1 month
Covid-19 vaccine status assessment	Assess if the patient received Covid-19 vaccine, or not.	Day 1

Collaborators and Investigators

• Sponsor: Alexandria University

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2022
• Primary Completion (Estimated): February 1, 2024
• Study Completion (Estimated): April 1, 2024

Study Registration Dates

• First Submitted: December 15, 2022
• First Submitted That Met QC Criteria: January 21, 2023
• First Posted (Actual): January 25, 2023

Study Record Updates

• Last Update Posted (Estimated): December 11, 2023
• Last Update Submitted That Met QC Criteria: December 7, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Cyclosporine; Lipoproteins; Obese patients
• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Syndrome; Nephrotic Syndrome; Nephrosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Antifungal Agents; Calcineurin Inhibitors; Cyclosporine; Cyclosporins
• Other Study ID Numbers: 0107113

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
• product manufactured in and exported from the U.S.: No