Fosrenol for Enhancing Dietary Protein Intake in Hypoalbuminemic Dialysis Patients (FrEDI) Study
Condition: End-Stage Renal Disease
MeSH terms: Kidney Diseases; Kidney Failure, Chronic
Study type: Interventional

Summary: 
      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: 
      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:

        1. 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.

        2. 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.

        3. 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.

        4. 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:

        1. Routine safety measures for food ingestion and binder administration

        2. 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.
    

Intervention name(s): Meals during hemodialysis accompanied by lanthanum carbonate to control phosphorus
Intervention type(s): Other
Intervention description(s): 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
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Supportive Care
Keywords: 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