Efficacy and Safety of Cholestyramine in the Management of Hyperphosphatemia in Adult Hemodialysis Patients

Chronic Kidney Diseases Clinical Trial

Official title:

Efficacy and Safety of Cholestyramine in the Management of Hyperphosphatemia in Adult Hemodialysis Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05577507
• Other study ID #: RHDIRB2020110301 REC#102
• Status: Completed
• Phase: Phase 4
• Start date: March 30, 2023
• Est. completion date: June 30, 2023

Study information

• Verified date: February 2024
• Source: Ain Shams University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of the study is to evaluate the efficacy and safety of cholestyramine in the management of hyperphosphatemia in hemodialysis patients. Colestilan is a non-metallic phosphate binder that acts as an anion-exchange resin. Colestilan itself is not absorbed after oral administration, and it is able to bind dietary phosphate within the gastrointestinal tract and thus prevent absorption of the mineral. Initial, Phase II, studies showed that it reduces serum phosphorus levels in dialysis patients with hyperphosphatemia without affecting serum calcium levels. There are no studies conducted about the feasibility and efficacy of cholestyramine as an oral phosphate binder in hemodialysis patients. Relying on the efficacy and safety of bile acid sequestrants such as colestilan and colestipol in the management of hyperphosphatemia and hypercholesterolemia in hemodialysis patients, cholestyramine is selected to be studied in hemodialysis patients. A total of 80 patients will be recruited and divided into 2 groups: - Group 1: (cholestyramine 12 gram), 40 patients will take a dose of cholestyramine 4-gram sachet in 150-200 ml water or juice three times daily within meals as an add on therapy with standard therapy calcium-based phosphate binder (Calcimate). Group 2: Control group, 40 patients will take only the standard therapy calcium-based phosphate binder (Calcimate). Time of the trial will be two months (8 weeks trial period) Baseline characteristics: The following data will be collected from all patients at baseline 1. Age, sex, weight, duration of ESRD and hemodialysis comorbidities. 2. Dialysis duration, serum phosphate level, serum calcium level, iPTH, BUN, Cr (mg/d L), Albumin (mg/d L), Hb (g m%), renal function test, liver function test, blood glucose level, TG, total cholesterol level, LDL-C, HDL.C. After the end of trial, we will examine if cholestyramine has a significant efficacy on reducing serum phosphate level in adult hemodialysis patients.

Description:

Chronic kidney disease-mineral and bone disorder (CKD-MBD) is characterized by progressive loss of renal function as well as dysregulation of mineral and bone metabolism, leading frequently to hyperphosphatemia. Multiple studies have consistently shown that hyperphosphatemia is associated with cardiovascular events and increased morbidity and mortality in end-stage renal disease (ESRD) patients. Importantly, use of phosphate binding agents and reduction of serum phosphate concentration are associated with a lower risk of mortality. The most widely used phosphate binders are calcium-based, although they are frequently associated with hypercalcemia and vascular calcification. Bile acid sequestrates like colestipol, colestilan and cholestyramine are pharmacologic molecules that bind to bile acids in the intestine resulting in the interruption of bile acid homeostasis and, consequently, reduction in low-density lipoprotein cholesterol levels in hypercholesterolemia. Colestilan is a non-metallic phosphate binder that acts as an anion-exchange resin. Colestilan itself is not absorbed after oral administration, and it is able to bind dietary phosphate within the gastrointestinal tract and thus prevent absorption of the mineral. Initial, Phase II, studies showed that it reduces serum phosphorus levels in dialysis patients with hyperphosphatemia without affecting serum calcium levels. There are no studies conducted about the feasibility and efficacy of cholestyramine as an oral phosphate binder in hemodialysis patients. Relying on the efficacy and safety of bile acid sequestrants such as colestilan and colestipol in the management of hyperphosphatemia and hypercholesterolemia in hemodialysis patients, cholestyramine is selected to be studied in hemodialysis patients. The aim of the study is to evaluate the efficacy and safety of cholestyramine in the management of hyperphosphatemia in hemodialysis patients. A total of 80 patients will be recruited and divided into 2 groups: - Group 1: (cholestyramine 12 gram), 40 patients will take a dose of cholestyramine 4-gram sachet in 150-200 ml water or juice three times daily within meals as an add-on therapy with standard therapy calcium-based phosphate binder (Calcimate). Group 2: Control group, 40 patients will take only the standard therapy calcium-based phosphate binder (Calcimate). Time of the trial will be two months (8 weeks trial period) Baseline characteristics: The following data will be collected from all patients at baseline 1. Age, sex, weight, duration of ESRD and hemodialysis comorbidities. 2. Dialysis duration, serum phosphate level, serum calcium level, iPTH, BUN, Cr (mg/d L), Albumin (mg/d L), Hb (g m%), renal function test, liver function test, blood glucose level, TG, total cholesterol level, LDL-C, HDL.C. After the end of trial, we will examine if cholestyramine has a significant efficacy on reducing serum phosphate level in adult hemodialysis patients. Parameters will be collected from all patients after 8-week trial period: Serum phosphate, serum calcium, iPTH, LDL, TG and total cholesterol level

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: June 30, 2023
• Est. primary completion date: May 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• • Patients aged =18 years with CKD stage (4&5)
• Serum phosphate level = 5.5 mg/dL
• Serum LDL-C level =1.82 mmol/L (70 mg/dL)
• Hemodialysis frequency 3 times per week or more.
• Hemodialysis in the last 3 months or longer.

Exclusion Criteria:

• Patients are excluded if they have a history of clinically significant gastrointestinal motility disorder, dysphagia, or swallowing disorder. 2-patients require warfarin or digoxin treatment. 3- Patients have a history of alcohol or substance abuse 4- Patients receiving calcimimetics. 5- Pregnant patients or patients planning pregnancy. 6- Patients have Triglyceride level above 300 (mg/dl)

Related Conditions & MeSH terms

• Chronic Kidney Diseases
• Hemodialysis Complication
• Hyperphosphatemia
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Drug:
• Cholestyramine Resin 4000 MG [Questran]
cholestyramine 4 gram sachets (questran) will be administered orally on 150 ml water three times daily for 8 weeks period trial
• Calcium Carbonate 500 MG Oral Tablet
control group will administer standard therapy calcium carobonate as calcium based phosphate binder 500 mg three times daily within meals

Locations

Country	Name	City	State
Egypt	Ain Shams university	Cairo

Sponsors (1)

Lead Sponsor	Collaborator
Ain Shams University

Country where clinical trial is conducted

Egypt, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	serum phosphate level	measuring serum phosphate level at baseline and after 8 weeks trial period to evaluate serum phosphate reduction by cholestyramine	8 weeks trial period
Primary	serum calcium level	measuring serum calcium level at baseline and after 8 weeks trial period to evaluate serum calcium reduction by cholestyramine	8 weeks trial period
Primary	iPTH	measuring iPTH level at baseline and after 8 weeks trial period to evaluate iPTH reduction by cholestyramine	8 weeks trial period
Secondary	Lipid Profile ( triglyceride level , LDL ,HDL ,Total cholesterol )	measuring LDL , total cholesterol reduction after using cholestyramine for 8 weeks trial period	8 weeks trial period

External Links

•   Dose of cholestyramine and frequency of administration
•   evaluation of bile acid sequestrants as colestilan as phosphate binders