Fosrenol for Enhancing Dietary Protein Intake in Hypoalbuminemic Dialysis Patients (FrEDI) Study

Study Overview
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Brief Summary
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Protein-energy wasting, as reflected by a serum albumin <4.0 g/dL, is very common in maintenance hemodialysis (MHD) patients and associated with poor clinical outcomes including high death rates. Hyperphosphatemia, reflected by serum phosphorus level >5.5 mg/dL, is also common disorder and associated with increased death risk in the same population. The traditional dietary intervention to control hyperphosphatemia is to restrict protein intake. This, however, may worsen protein-energy wasting as recently showed in large epidemiologic data, which indicated that the best survival was observed in MHD patients with increased protein intake while serum phosphorus could be controlled. We hypothesize that the provision of high protein diet will be possible if a potent phosphorus binder (Fosreonl™) will be prescribed simultaneously. Hence, we propose to conduct a randomized controlled trial in 110 hypoalbuminemic (albumin <4.0 mg/dL) MHD patients in several DaVita dialysis facilities in Los Angeles South Bay area. After 1:1 randomization, we will provide the participating subjects (the INTERVENTION group) with 8 weeks of high protein meals in form of prepared meal boxes (50 g protein, 850 Cal, and a phosphorus to protein ratio of <10 mg/gm) during each hemodialysis treatment, along with 0.5 to 1.5 g Fosrenol, to be titrated if necessary; as well as dietary counselling to maintain a high dietary protein intake at home (with same or similar binder regimen) for 8 weeks and to avoid food items with high phosphorus based additives. Meals will be prepared at Harbor-UCLA GCRC Bio-nutrition Department. We have reviewed and tested the feasibility of meal preparation and distribution system and the related logistics. The CONTROL group will also receive meal boxes but the meal contains low Calorie (<50 Cal) and almost zero protein (<1 g) diet (such as salads) during each hemodialysis treatment. These patients will continue their pre-existing phosphorus control regimens. As outcome variables, we will examine change in serum albumin over the 8 weeks of intervention. We will also examine changes in dietary protein and serum phosphorus in the 2 groups after 8 weeks of intervention. Quality of life and patient satisfaction will also be examined before and towards the end of the intervention phase. Given our ongoing 2-year study with a similar operation known as the AIONID Study and given DaVita dieticians'' collaboration and support, we anticipate successful recruitment, retention and data analyses within 8 to 12 months.

Detailed Description
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RATIONALE: Based on the hypothesis that the efficacy and potency of Fosrenol enables increasing dietary protein intake and provision of meals during dialysis treatment for improving nutritional status in malnourished dialysis patients with a low serum albumin (<4.0 g/dL) while serum phosphorus can be effectively controlled with the target range of 3.5 to 5.5 mg/dL. STUDY PROCEDURE: In all subjects: Recommend adequate dietary protein intake to achieve or maintain an nPCR (nPNA) above 1.0 g/kg/day for 2 months. Encourage aggressive increase in protein intake while avoiding high phos/protein ratio esp. higher intake of egg whites, meat, fish, poultries, legumes, etc. via counseling by renal dietician (RD) and/or study staff. Both groups will receive free meal boxes during the first 60 min of HD treatment for 8 weeks (24 meals during 24 HD treatment sessions). Cases will receive high protein meals ( 50 gm, with phos/protein ratio <10 mg//gm), whereas controls will receive salad with almost no protein. In CASES (n=55): Switch binder simultaneously to (or start) Fosrenol 500 mg to 1,500 per meal/snack, according to the meal size at different times of the day. Recommend crushing the pills using the pill-crusher that will be provided to subjects, and recommend placing or sprinkling Fosrenol pieces on the food. Titrate the dose every 2 weeks according to serum phosphorus. In CONTROLLS (n=55): Continue the same binder (other than Fosrenol). In All subjects: Titrate the binder as indicated to control serum phosphorus <5.5 mg/dL. SAFETY ENDPOINTS: Routine safety measures for food ingestion and binder administration Bi-weekly measures of minerals and monthly measures of PTH STATISTICAL METHODS: The t test, the chi square test, and the Mann-Whitney rank sum test to compare the baseline characteristics of intervention and control participants in serum albumin and other measures. To simplify presentation of results, some Likert scale responses will be dichotomized. The corresponding P values will be based on the complete ordinal scales used by participants to respond to questions quality of life, satisfaction, and food intake and about how often they eat meals from specific fast-food restaurants.

Official Title
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Fosrenol for Enhancing Dietary Protein Intake in Hypoalbuminemic Dialysis Patients (FrEDI) Study: An Investigator Initiated Study

Conditions
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End-Stage Renal Disease

Intervention / Treatment
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* Other: Meals during hemodialysis accompanied by lanthanum carbonate to control phosphorus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Prevalent hypoalbuminemic hemodialysis patients with a serum albumin <4.0 g/dL and capable of oral food intake Adult (18-85 years) hemodialysis patients for 3 months or longer, capable of eating food independently Protein energy wasting as evident by serum albumin <4.0 g/dL Not receiving Fosrenol for the past 2 weeks Exclusion Criteria: Not willing to sign the written consent form Any condition that can interfere with increasing dietary protein intake, e.g. inability to eat or to maintain ingested food (OK to be on vitamin D agents including paricalcitol, calcitriol, doxercalciferol, ergocalciferol and cholecalciferol; or cinacalcet)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intervention Arm<br>1. Treatment Arm (CASES) will receive high protein meals during thrice weekly hemodialysis in-center (each meal includes  50 g of protein,  850 Cal, and phos/protein ratio <10 mg/g) PLUS dietary counseling to continue similar high protein intake with low phosphorus to protein ratio and to avoid foods with high preservative content. Fosrenol 1.0 to 1.5 g per meal will be prescribed (use of pill crusher will be recommended) and will be titrated based on bi-weekly phosphorus levels. | Other: Meals during hemodialysis accompanied by lanthanum carbonate to control phosphorus<br>* Based on the hypothesis that the efficacy and potency of Fosrenol enables increasing dietary protein intake and provision of meals during dialysis treatment for improving nutritional status in malnourished dialysis patients with a low serum albumin (<4.0 g/dL) while serum phosphorus can be effectively controlled with the target range of 3.5 to 5.5 mg/dL<br>|
| Active Comparator: Control Arm (CONTROLS)<br>2. Control Arm (CONTROLS) will receive salad boxes in-center (no protein, low calorie) and routine dietary counseling and will continue pre-existing phosphorus binder regimen. | Other: Meals during hemodialysis accompanied by lanthanum carbonate to control phosphorus<br>* Based on the hypothesis that the efficacy and potency of Fosrenol enables increasing dietary protein intake and provision of meals during dialysis treatment for improving nutritional status in malnourished dialysis patients with a low serum albumin (<4.0 g/dL) while serum phosphorus can be effectively controlled with the target range of 3.5 to 5.5 mg/dL<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1. Change in serum albumin by +0.2 g/dl or higher over 2 months, i.e., from baseline (Month 0) to Month 2 (main outcome measure) |  | 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2. Percentage of serum phosphorus between 3.5 and 5.5 mg/dL |  | 2 months | 
| 3. Change in nPCR (nPNA) by +0.1 g/kg/day |  | 2 months | 
| 4. Change in protein intake via food frequency questionnaire x 2 (baseline vs. after 2 months) |  | 2 months | 
| 5. Change in post-dialysis dry weight |  | 2 months | 
| 6. Changes in calcium, PTH, and alkaline phosphatase |  | 2 months | 
| 7. Patients satisfaction and quality of life (KDQOL36) |  | 2 months | 
| 8. RD and MD satisfaction per questionnaires |  | 2 months | 
| 9. Change in other nutritional or inflammatory markers (CRP, TIBC, MIS, SGA) |  | 2 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypoalbuminemia, Hyperphosphatemia, Phosphorus, Protein, CKD, Dialysis, Meals, Lanthanum, End-Stage Renal Disease (ESRD), Dietary Protein Intake (DPI), Dietary Phosphorus Binding (DPB), Protein-Energy Wasting (PEW), Sources of Dietary Phosphorus