Ignite Creation Date:
2024-05-05 @ 11:29 PM
Last Modification Date:
2024-10-26 @ 10:34 AM
Study NCT ID:
NCT01341678
Status:
COMPLETED
Last Update Posted:
2014-02-11
First Post:
2011-04-23
Brief Title:
Circadian Rhythm Modulation by Dietary Phosphorus in Chronic Kidney Disease
Sponsor:
Geoffrey Block
Organization:
Denver Nephrologists PC
Study Overview
Official Title:
Circadian Rhythm Modulation by Dietary Phosphorus in Chronic Kidney Disease CKD
Status:
COMPLETED
Status Verified Date:
2011-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purpose of this study is to describe the circadian rhythm of serum and salivary phosphorus in patients with chronic kidney disease and determine its modification in response to changes in dietary phosphate load
Detailed Description:
In normal healthy individuals there is a 12-hour and 24-hour circadian rhythm of serum phosphorus serum P with a nadir in early-mid morning a rise to a minor peak in the afternoon around 400PM and a further rise to a major peak just after midnight In a study of 6 healthy male patients Portale et al found that the 12-hour component is modified by dietary P intake whereas the 24-hour rhythm in serum P is independent of the intake of phosphorus Additionally this trial demonstrated a large swing in amplitude between peak and nadir serum P in the normal healthy subjects 12 mgdL and also demonstrated a large difference in mean 24-hour serum P with normal vs high dietary P intake however no difference in fasting AM serum P results was observed These findings may suggest the poor performance of serum P as a biomarker of intervention aimed at P load reductions via treatment options such as phosphate binders or salivary P-binder chewing gum
While the circadian rhythm of serum phosphorus in healthy individuals has been described no data exists on the circadian rhythm of salivary P nor has the circadian rhythm of serum P been described in subjects with moderate kidney disease exposed to various levels of dietary P exposure In recent years saliva has been found to be a good indicator of the plasma level of various substances one of which being phosphorus Specifically increased salivary P excretion has been reported in patients with CKD Daily salivary secretion volume ranges between 500 - 700 mLday therefore salivary P has recently been established as a previously unaccounted for source of phosphorus contributing a conservative estimate of 366 mgday and 2500 mgweek of immediately bioavailable phosphorus
There is a significant amount of data available regarding the utilization of serum P as a biomarker of intervention aimed at phosphorus load reductions however minimal information regarding the timing of phosphorus measurements ie when serum P is assessed during a 24-hour period is available Wolf et al have demonstrated that despite an 80 reduction in urinary P with dietary P restriction and treatment with P binders over a 2-week period there was no change in serum P or in FGF-23 However both biomarkers were sampled once every 3 days over a 2-week period without regard to the time of day This suggests that single time point measurements of serum P in patients with CKD do not accurately reflect phosphate load As such it is plausible that mean 24-hour serum P or mean 24-hour serum FGF-23 are better markers of phosphorus load in CKD than single measurements
Additionally there are no published indicators of 24-hour mean serum P in patients with CKD It is reasonable that either salivary P or FGF-23 might be optimal predictors Therefore this study will examine the 24-hour mean serum P and its relationship to both single and mean salivary P values as well as single and mean FGF-23 values in the controlled setting of specific low normal and high phosphate diets This examination and further understanding of mean serum P values and how they relate to the biomarkers of FGF-23 and salivary P with variation in intestinal phosphate load will inform the design and conduct of future interventional trials assessing reductions in phosphorus load
This study is a single-center exploratory trial in subjects with reduced kidney function A total of 9 eligible subjects with an estimated GFR between 30 - 45 mLmin 10 and 3 normal healthy subjects as control will be sequentially exposed to three different Phosphorus diets normal low and high
Study assessments will occur in both the inpatient observation and outpatient clinic setting A total of four observational inpatient days Days 7 12 18 and 29 will be required throughout the study Serum saliva and urine specimens will be collected at specified time-points beginning at the Day 1 visit and concluding at the Day 36 Follow-Up visit During the inpatient study visits blood urine and salivary samples will be collected every 4 hours
Subjects will be provided with specific diets created using a 1500 mg P base diet supplemented with NeutraPhos to achieve the desired P load as described in the table below During treatment period 2 Low P Diet patients will receive an alternative low P diet and additionally receive lanthanum carbonate 1000 mg with each meal to ensure a low dietary P load
While the circadian rhythm of serum phosphorus in healthy individuals has been described no data exists on the circadian rhythm of salivary P nor has the circadian rhythm of serum P been described in subjects with moderate kidney disease exposed to various levels of dietary P exposure In recent years saliva has been found to be a good indicator of the plasma level of various substances one of which being phosphorus Specifically increased salivary P excretion has been reported in patients with CKD Daily salivary secretion volume ranges between 500 - 700 mLday therefore salivary P has recently been established as a previously unaccounted for source of phosphorus contributing a conservative estimate of 366 mgday and 2500 mgweek of immediately bioavailable phosphorus
There is a significant amount of data available regarding the utilization of serum P as a biomarker of intervention aimed at phosphorus load reductions however minimal information regarding the timing of phosphorus measurements ie when serum P is assessed during a 24-hour period is available Wolf et al have demonstrated that despite an 80 reduction in urinary P with dietary P restriction and treatment with P binders over a 2-week period there was no change in serum P or in FGF-23 However both biomarkers were sampled once every 3 days over a 2-week period without regard to the time of day This suggests that single time point measurements of serum P in patients with CKD do not accurately reflect phosphate load As such it is plausible that mean 24-hour serum P or mean 24-hour serum FGF-23 are better markers of phosphorus load in CKD than single measurements
Additionally there are no published indicators of 24-hour mean serum P in patients with CKD It is reasonable that either salivary P or FGF-23 might be optimal predictors Therefore this study will examine the 24-hour mean serum P and its relationship to both single and mean salivary P values as well as single and mean FGF-23 values in the controlled setting of specific low normal and high phosphate diets This examination and further understanding of mean serum P values and how they relate to the biomarkers of FGF-23 and salivary P with variation in intestinal phosphate load will inform the design and conduct of future interventional trials assessing reductions in phosphorus load
This study is a single-center exploratory trial in subjects with reduced kidney function A total of 9 eligible subjects with an estimated GFR between 30 - 45 mLmin 10 and 3 normal healthy subjects as control will be sequentially exposed to three different Phosphorus diets normal low and high
Study assessments will occur in both the inpatient observation and outpatient clinic setting A total of four observational inpatient days Days 7 12 18 and 29 will be required throughout the study Serum saliva and urine specimens will be collected at specified time-points beginning at the Day 1 visit and concluding at the Day 36 Follow-Up visit During the inpatient study visits blood urine and salivary samples will be collected every 4 hours
Subjects will be provided with specific diets created using a 1500 mg P base diet supplemented with NeutraPhos to achieve the desired P load as described in the table below During treatment period 2 Low P Diet patients will receive an alternative low P diet and additionally receive lanthanum carbonate 1000 mg with each meal to ensure a low dietary P load
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None