Healthy Combine Study
Condition: Healthy
Study type: Interventional
Phase: Phase 1

Summary: 
      STUDY SUMMARY Title: EFFECTS OF NICOTINAMIDE AND LANTHANUM CARBONATE ON PHOSPHORUS
      HOMEOSTASIS Protocol Number:STU00090161 Phase: Phase 1, detailed physiologic study
      Methodology: double blind, randomized, placebo-controlled, 2x2 factorial Study Duration:
      12-18 months (to complete the entire study protocol) Study Center: Single-center Objectives:
      Define short-term effects of the interventions (lanthanum carbonate and nicotinamide) on
      indices of phosphate handling Number of Subjects: 80 Diagnosis and Main Inclusion Criteria:
      Healthy volunteers Study Product(s), Dose,Route, Regimen: Nicotinamide, 750 mg by mouth twice
      daily, Lanthanum carbonate, Fosrenol, 1000 mg by mouth three times daily with meals Duration
      of administration: 2 weeks (length of time study participants are enrolled in study)
      Reference therapy: reference is a placebo Statistical Methodology: Repeated measures analysis
      using mixed linear models
    

Detailed description: 
      Chronic kidney disease (CKD) is a growing public health problem that increases risks of
      endstage renal disease (ESRD), cardiovascular disease (CVD), fractures, and death, and it
      poses an enormous financial burden on the US health system. Existing therapies modestly
      impact outcomes. Novel strategies targeting CKD-specific mechanisms are urgently needed to
      improve health and reduce cost.

      CKD is complicated by disordered mineral metabolism, characterized by abnormal calcium and
      phosphate homeostasis, calcitriol and klotho deficiency, and elevated levels of parathyroid
      hormone (PTH) and fibroblast growth factor 23 (FGF23). Elevated FGF23 is the earliest and
      most common manifestation of disordered mineral metabolism. Observational studies report
      independent associations between elevated phosphate and FGF23 blood levels and increased
      risks of ESRD, CVD and death. As potential explanatory mechanisms, phosphate excess induces
      arterial stiffness due to vascular calcification, and FGF23 excess contributes directly to
      the pathogenesis of left ventricular hypertrophy (LVH). Together, these effects promote CVD
      events and death.

      Dietary phosphate absorption is a modifiable determinant of phosphate and FGF23 levels. Small
      studies of short duration suggest that phosphate binders and dietary phosphate modification
      in CKD can lower phosphate and FGF23 blood levels by reducing paracellular absorption of
      phosphate in the gut. However, animal studies demonstrate that compensatory upregulation of
      transcellular phosphate absorption via the sodium phosphate co-transporter, NPT2b, reduces
      the efficacy of these approaches. Since nicotinamide lowers plasma phosphate by reducing gut
      expression of NPT2b,the investigators hypothesize that use of nicotinamide combined with
      phosphate binders on a background of dietary phosphate moderation will most effectively
      reduce phosphate and FGF23 blood levels in CKD. The investigators plan to advance this
      approach in future randomized clinical trials.

      The objective of this study is to perform a detailed physiologic study of healthy volunteers
      to assess the short-term effects of nicotinamide alone, lanthanum carbonate alone, or both in
      combination, on phosphate homeostasis. The results from healthy volunteers will provide
      information needed for optimal design of studies for patients with CKD.
    

Intervention name(s): Nicotinamide; Lanthanum Carbonate; Lanthanum Carbonate Placebo; Nicotinamide Placebo
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Nicotinamide tablet; Lanthanum Carbonate tablet; Sugar pill manufactured to look like Lanthanum Carbonate tablet; Sugar pill manufactured to look like Nicotinamide tablet
Other intervention name(s): Fosrenol; Placebo (for Lanthanum Carbonate 500mg tablet); Placebo (for Nicotinamide 750mg tablet)
Intervention MeSH terms: Niacinamide; Niacin; Nicotinic Acids
Allocation: Randomized
Intervention model: Factorial Assignment
Intervention model description: Double blind, randomized, placebo-controlled, 2x2 factorial
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Phosphorus Homeostasis; FGF23; Vitamin D