Trace Element Replenishment Study in Hemodialysis Patients

Study Overview
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Brief Summary
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A pilot randomized trial that compares a new renal nutritional supplement with the standard renal vitamin. The primary objective is to compare two doses (medium and high) of the new supplement with the renal vitamin currently being prescribed to people with End Stage Renal Disease (ESRD). Secondary objective is to demonstrate the feasibility of recruitment for a definitive larger trial.

Detailed Description
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People with severe kidney disease follow a restricted diet aimed at reducing intake of sodium, potassium and phosphate. These dietary restrictions require reducing their intake of many fresh fruits and vegetables, which may lead to nutritional deficiency. Although the potential for malnutrition in people with kidney disease is well recognized, blood levels of most vitamins and trace elements are rarely measured. Instead, most North Americans with severe kidney disease are routinely prescribed a renal vitamin such as Replavite which contains a mixture of B and C vitamins. Recent evidence (including our work; see http://www.biomedcentral.com/bmcmed/subjects/nephrology) indicates that people with severe kidney disease are often deficient in several other biologically essential substances (selenium, zinc) that are readily amenable to supplementation. Pilot data from the Northern Alberta Renal Program (NARP) indicate that approximately 90% of patients have zinc levels below the lower limit of normal; findings for selenium are similar. Potential benefits of zinc supplementation include improvements in immune function, taste sensitivity (perhaps reducing dietary sodium intake), and improved appetite. Potential benefits of selenium supplementation include reductions in the risk of vascular disease and infection. Supplementation with vitamin E was shown in a randomized trial to reduce serious cardiovascular morbidity in people with kidney failure, but is not routinely used in dialysis patients. This suggests that supplementation of zinc, selenium, and vitamin E has theoretical benefits in kidney failure. Since patients with kidney failure already take many medications, it is logical to combine any new nutritional supplements with the ingredients of the standard renal vitamin to reduce pill burden. This protocol concerns a novel nutritional supplement consisting of zinc, selenium and vitamin E in addition to the contents of the standard renal supplement of B and C vitamins. This pilot randomized, double blind trial will compare 2 doses of the new supplement with the standard renal vitamin. 2.0 Objectives: Primary objective: compare two formulations of the new supplement (low and medium doses of zinc and selenium) with standard treatment (Replavite or equivalent renal vitamin). Secondary objective: demonstrate the feasibility of recruitment for a definitive larger trial

Official Title
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Trace Element Replenishment Study in Hemodialysis Patients

Conditions
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End Stage Renal Disease

Intervention / Treatment
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* Dietary Supplement: Low dose: supplemental zinc, selenium and vitamin E
* Dietary Supplement: Standard renal vitamin: B and C renal vitamin
* Dietary Supplement: Medium dose: supplemental zinc, selenium and vitamin E


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Stable on hemodialysis for 3 to 36 months Age greater or equal to 18 years Receiving Replavite or equivalent renal vitamin at baseline Receiving 3 dialysis treatments per week Exclusion Criteria: Pregnant (sexually active pre-menopausal females must have negative serum pregnancy test at baseline) Pregnancy, kidney transplantation, a dialysis modality switch, or gastrointestinal surgery planned within 6 months Known allergy to corn starch Known allergy to zinc, selenium, vitamin E or renal vitamin. Projected life expectancy of <6 months Any other conditions or procedures that, in the opinion of the investigator, would impede absorption of the study product. Participants already taking a vitamin E, zinc or selenium supplement (alone or included in another multi-vitamin). Individuals with a history of head or neck cancer in the past 5 years. Ostomy or short gut syndrome. Enroll in another (interventional) trial.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low dose<br>Standard renal vitamin plus low dose zinc and selenium plus vitamin E 1 capsule p.o, daily | Dietary Supplement: Low dose: supplemental zinc, selenium and vitamin E<br>* ZINC 25mg (AS ZINC SULFATE) SELENIUM 50 mcg (AS SODIUM SELENITE) VITAMIN E (D-ALPHA-TOCOPHEROL) (AS SUCCINATE) 250 IU<br>Dietary Supplement: Standard renal vitamin: B and C renal vitamin<br>* BIOTIN 300 MCG D-PANTOTHENIC ACID (CALCIUM D-PANTOTHENATE) 10 MG FOLIC ACID 1 MG NIACINAMIDE 20 MG VITAMIN B1 (THIAMINE MONONITRATE) 1.5 MG VITAMIN B12(CYANOCOBALAMIN) 6 MCG VITAMIN B2 (RIBOFLAVIN) 1.7 MG VITAMIN B6 (PYRIDOXINE HYDROCHLORIDE) 10 MG VITAMIN C (ASCORBIC ACID) 100 MG INERT FILLER (CORNSTARCH)<br>* Other names: Replavite;|
| Experimental: Medium dose<br>Standard renal vitamin plus medium doses of zinc and selenium plus vitamin E 1 capsule p.o, daily | Dietary Supplement: Standard renal vitamin: B and C renal vitamin<br>* BIOTIN 300 MCG D-PANTOTHENIC ACID (CALCIUM D-PANTOTHENATE) 10 MG FOLIC ACID 1 MG NIACINAMIDE 20 MG VITAMIN B1 (THIAMINE MONONITRATE) 1.5 MG VITAMIN B12(CYANOCOBALAMIN) 6 MCG VITAMIN B2 (RIBOFLAVIN) 1.7 MG VITAMIN B6 (PYRIDOXINE HYDROCHLORIDE) 10 MG VITAMIN C (ASCORBIC ACID) 100 MG INERT FILLER (CORNSTARCH)<br>* Other names: Replavite;Dietary Supplement: Medium dose: supplemental zinc, selenium and vitamin E<br>* ZINC 50 mg (AS ZINC SULFATE) SELENIUM 75 mcg (AS SODIUM SELENITE) VITAMIN E (D-ALPHA-TOCOPHEROL) (AS SUCCINATE) 250 IU<br>|
| Active Comparator: Standard treatment<br>Standard renal vitamin 1 capsule p.o, daily | Dietary Supplement: Standard renal vitamin: B and C renal vitamin<br>* BIOTIN 300 MCG D-PANTOTHENIC ACID (CALCIUM D-PANTOTHENATE) 10 MG FOLIC ACID 1 MG NIACINAMIDE 20 MG VITAMIN B1 (THIAMINE MONONITRATE) 1.5 MG VITAMIN B12(CYANOCOBALAMIN) 6 MCG VITAMIN B2 (RIBOFLAVIN) 1.7 MG VITAMIN B6 (PYRIDOXINE HYDROCHLORIDE) 10 MG VITAMIN C (ASCORBIC ACID) 100 MG INERT FILLER (CORNSTARCH)<br>* Other names: Replavite;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with zinc deficiency | Proportion of participants with zinc deficiency in the combined experimental arms compared to the proportion of participants with zinc deficiency in the active comparator arm. | 90 days following baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with zinc deficiency | The proportion of participants with zinc deficiency in each arm compared to each other arm at each time point. | 180 days following baseline | 
| Proportion of participants with selenium deficiency | The proportion of participants with selenium deficiency in each arm compared to each other arm at each time point. | 90 days and 180 days following baseline | 
| Zinc | Zinc concentration in each arm compared to each other arm. | 90 days and 180 days following baseline | 
| Selenium | Selenium concentration measured in each arm compared to each other arm. | 90 days and 180 days following baseline |