Ignite Creation Date:
2024-05-05 @ 5:15 PM
Last Modification Date:
2024-10-26 @ 9:29 AM
Study NCT ID:
NCT00410007
Status:
COMPLETED
Last Update Posted:
2018-03-20
First Post:
2006-12-10
Brief Title:
The Effect of High and Low Sodium Intake on Urinary Aquaporin-2 in Autosomal Dominant Polycystic Kidney Disease
Sponsor:
Carolina Cannillo
Organization:
Regional Hospital Holstebro
Study Overview
Official Title:
The Effect of High and Low Sodium Intake on Urinary Aquaporin-2 in Autosomal Dominant Polycystic Kidney Disease During Basal Conditions and After Hypertonic Saline Infusion
Status:
COMPLETED
Status Verified Date:
2018-03
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 aim of the study is to test the following hypotheses
1 that the function andor regulation of AQP2 and or ENaC in the principal cells is abnormal in autosomal dominant polycystic kidney disease
2 if an abnormal function of the principal cells is present in autosomal dominant polycystic kidney disease this will become more pronounced at high and low sodium intake
1 that the function andor regulation of AQP2 and or ENaC in the principal cells is abnormal in autosomal dominant polycystic kidney disease
2 if an abnormal function of the principal cells is present in autosomal dominant polycystic kidney disease this will become more pronounced at high and low sodium intake
Detailed Description:
Recruitment
The patients with ADPKD are recruited from the Outpatient Nephrology Clinic of the Department of Medicine Holstebro Hospital Holstebro Denmark The control subjects are recruited by advertising in public institutions and private companies
Number of Subjects
A difference in u-AQP2CR of 40 ngmmol is considered the minimal relevant difference A sample size of 10 subjects who can be evaluated has 80 power to detect this difference assuming a level of significance of 5 and an SD of 30 ngmmol Because a few subjects are expected to drop out 14-15 subjects will be included in each group
Experimental Procedure Before the Study Day
Five days before the study day the subjects collect a standardized HS 300 mmol sodiumday175 g saltday or LS 30 mmol sodiumday18 g saltday 4-day diet from the hospital kitchen Depending on the individually estimated energy requirement the participants are given either a diet of 8000 or 11000 kJday The energy distribution is 55 carbohydrates 15 proteins and 30 lipids The 4-day diet is started the following morning The fluid intake is also standardized during the 4 days The subjects are asked to drink exactly 250 ml1000 kJday and to abstain from coffee tea and alcoholic beverages The subjects are instructed to keep their physical activity unchanged during the two experiments and to abstain from hard training The subjects have to collect their urine for 24 h the day before the study day
Experimental Procedure on the Study Day
On the study day the subjects are asked to drink 175 ml of water every 30 min from 700 AM The subjects arrive at the department at 800 AM Peripheral iv lines are inserted into the antecubital veins of both forearms one for infusion of 51Cr-EDTA and hypertonic saline and one for withdrawal of blood samples The subjects will be kept in the supine position from 800 AM to 130 PM except during voiding which will take place in the sitting or standing position At 830 AM a priming dose of 51Cr-EDTA is administered followed by sustained infusion After 60 min of equilibration the study will continue with five clearance periods the first two of 30-min duration P1-P2 the last three of 60-min duration P3-P5 The first two clearance periods are baseline periods At 1030 AM 7 mlkg of 3 saline is given over 30 min Blood pressure and heart rate are measured every 30 min from 930 AM to 130 PM Urine is collected in each clearance period and analyzed for sodium osmolality u-AQP2 u-ENaC-betaCR u-cAMP u-PGE2 and 51CrEDTA Blood samples will be drawn every 30 min from 930 AM to 1030 AM and every hour from 1130 AM to 130 PM and will be analyzed for sodium osmolality and 51Cr-EDTA In addition analysis of p-AVP p-Renin p-ANG II p-Aldo p-ANP and p-BNP will be performed from blood samples drawn at 1030 AM 1130 AM 1230 PM and 130 PM
Statistics
Statistical analyses will be performed using SPSS version 15 SPSS Chicago IL Single baseline values are obtained by taking the weighted average of the measurements from the two baseline periods The baseline values of the two groups will be compared by Students t-test The baseline values during HS and LS intake will be compared by paired samples t-tests The investigators will use the General Linear Model Repeated Measures procedure in SPSS with time as the within-subject factor and group as the between-subject factor to compare the effect variables in patients and controls The changes in response to the hypertonic saline infusion in each group will be analyzed with the General Linear Model Repeated Measures procedure with time as the within-subject factor and paired samples t-tests with Bonferroni correction as post hoc tests P values Recruitment The patients with ADPKD will be recruited from the Outpatient Nephrology Clinic of the Department of Medicine Holstebro Hospital Holstebro Denmark The control subjects will be recruited by advertising in public institutions and private companies
Number of Subjects A difference in u-AQP2CR of 40 ngmmol is considered the minimal relevant difference A sample size of 10 subjects who could be evaluated has 80 power to detect this difference assuming a level of significance of 5 and an SD of 30 ngmmol Because a few subjects are expected to drop out 14-15 subjects will be included in each group
Experimental Procedure Before the Study Day Five days before the study day the subjects will collect a standardized HS 300 mmol sodiumday175 g saltday or LS 30 mmol sodiumday18 g saltday 4-day diet from the hospital kitchen Depending on the individually estimated energy requirement the participants will be given either a diet of 8000 or 11000 kJday The energy distribution will be 55 carbohydrates 15 proteins and 30 lipids The 4-day diet will start the following morning The fluid intake is also standardized during the 4 days The subjects are asked to drink exactly 250 ml1000 kJday and to abstain from coffee tea and alcoholic beverages The subjects will be instructed to keep their physical activity unchanged during the two experiments and to abstain from hard training The subjects have to collect their urine for 24 h the day before the study day
Experimental Procedure on the Study Day On the study day the subjects are asked to drink 175 ml of water every 30 min from 700 AM The subjects arrive at the department at 800 AM Peripheral iv lines will be inserted into the antecubital veins of both forearms one for infusion of 51Cr-EDTA and hypertonic saline and one for withdrawal of blood samples The subjects will be kept in the supine position from 800 AM to 130 PM except during voiding which will take place in the sitting or standing position At 830 AM a priming dose of 51Cr-EDTA is administered followed by sustained infusion After 60 min of equilibration the study will continue with five clearance periods the first two of 30-min duration P1-P2 the last three of 60-min duration P3-P5 The first two clearance periods are baseline periods At 1030 AM 7 mlkg of 3 saline is given over 30 min Blood pressure and heart rate will be measured every 30 min from 930 AM to 130 PM Urine is collected in each clearance period and analyzed for sodium osmolality u-AQP2 u-ENaC-betaCR u-cAMP u-PGE2 and 51CrEDTA Blood samples will be drawn every 30 min from 930 AM to 1030 AM and every hour from 1130 AM to 130 PM and will be analyzed for sodium osmolality and 51Cr-EDTA In addition analysis of p-AVP p-Renin p-ANG II p-Aldo p-ANP and p-BNP will be performed from blood samples drawn at 1030 AM 1130 AM 1230 PM and 130 PM
Statistics Statistical analyses will be performed using SPSS version 15 SPSS Chicago IL Single baseline values are obtained by taking the weighted average of the measurements from the two baseline periods The baseline values of the two groups will be compared by Students t-test The baseline values during HS and LS intake will be compared by paired samples t-tests The investigators will use the General Linear Model Repeated Measures procedure in SPSS with time as the within-subject factor and group as the between-subject factor to compare the effect variables in patients and controls The changes in response to the hypertonic saline infusion in each group will be analyzed with the General Linear Model Repeated Measures procedure with time as the within-subject factor and paired samples t-tests with Bonferroni correction as post hoc tests P values 005 will be considered significant
The patients with ADPKD are recruited from the Outpatient Nephrology Clinic of the Department of Medicine Holstebro Hospital Holstebro Denmark The control subjects are recruited by advertising in public institutions and private companies
Number of Subjects
A difference in u-AQP2CR of 40 ngmmol is considered the minimal relevant difference A sample size of 10 subjects who can be evaluated has 80 power to detect this difference assuming a level of significance of 5 and an SD of 30 ngmmol Because a few subjects are expected to drop out 14-15 subjects will be included in each group
Experimental Procedure Before the Study Day
Five days before the study day the subjects collect a standardized HS 300 mmol sodiumday175 g saltday or LS 30 mmol sodiumday18 g saltday 4-day diet from the hospital kitchen Depending on the individually estimated energy requirement the participants are given either a diet of 8000 or 11000 kJday The energy distribution is 55 carbohydrates 15 proteins and 30 lipids The 4-day diet is started the following morning The fluid intake is also standardized during the 4 days The subjects are asked to drink exactly 250 ml1000 kJday and to abstain from coffee tea and alcoholic beverages The subjects are instructed to keep their physical activity unchanged during the two experiments and to abstain from hard training The subjects have to collect their urine for 24 h the day before the study day
Experimental Procedure on the Study Day
On the study day the subjects are asked to drink 175 ml of water every 30 min from 700 AM The subjects arrive at the department at 800 AM Peripheral iv lines are inserted into the antecubital veins of both forearms one for infusion of 51Cr-EDTA and hypertonic saline and one for withdrawal of blood samples The subjects will be kept in the supine position from 800 AM to 130 PM except during voiding which will take place in the sitting or standing position At 830 AM a priming dose of 51Cr-EDTA is administered followed by sustained infusion After 60 min of equilibration the study will continue with five clearance periods the first two of 30-min duration P1-P2 the last three of 60-min duration P3-P5 The first two clearance periods are baseline periods At 1030 AM 7 mlkg of 3 saline is given over 30 min Blood pressure and heart rate are measured every 30 min from 930 AM to 130 PM Urine is collected in each clearance period and analyzed for sodium osmolality u-AQP2 u-ENaC-betaCR u-cAMP u-PGE2 and 51CrEDTA Blood samples will be drawn every 30 min from 930 AM to 1030 AM and every hour from 1130 AM to 130 PM and will be analyzed for sodium osmolality and 51Cr-EDTA In addition analysis of p-AVP p-Renin p-ANG II p-Aldo p-ANP and p-BNP will be performed from blood samples drawn at 1030 AM 1130 AM 1230 PM and 130 PM
Statistics
Statistical analyses will be performed using SPSS version 15 SPSS Chicago IL Single baseline values are obtained by taking the weighted average of the measurements from the two baseline periods The baseline values of the two groups will be compared by Students t-test The baseline values during HS and LS intake will be compared by paired samples t-tests The investigators will use the General Linear Model Repeated Measures procedure in SPSS with time as the within-subject factor and group as the between-subject factor to compare the effect variables in patients and controls The changes in response to the hypertonic saline infusion in each group will be analyzed with the General Linear Model Repeated Measures procedure with time as the within-subject factor and paired samples t-tests with Bonferroni correction as post hoc tests P values Recruitment The patients with ADPKD will be recruited from the Outpatient Nephrology Clinic of the Department of Medicine Holstebro Hospital Holstebro Denmark The control subjects will be recruited by advertising in public institutions and private companies
Number of Subjects A difference in u-AQP2CR of 40 ngmmol is considered the minimal relevant difference A sample size of 10 subjects who could be evaluated has 80 power to detect this difference assuming a level of significance of 5 and an SD of 30 ngmmol Because a few subjects are expected to drop out 14-15 subjects will be included in each group
Experimental Procedure Before the Study Day Five days before the study day the subjects will collect a standardized HS 300 mmol sodiumday175 g saltday or LS 30 mmol sodiumday18 g saltday 4-day diet from the hospital kitchen Depending on the individually estimated energy requirement the participants will be given either a diet of 8000 or 11000 kJday The energy distribution will be 55 carbohydrates 15 proteins and 30 lipids The 4-day diet will start the following morning The fluid intake is also standardized during the 4 days The subjects are asked to drink exactly 250 ml1000 kJday and to abstain from coffee tea and alcoholic beverages The subjects will be instructed to keep their physical activity unchanged during the two experiments and to abstain from hard training The subjects have to collect their urine for 24 h the day before the study day
Experimental Procedure on the Study Day On the study day the subjects are asked to drink 175 ml of water every 30 min from 700 AM The subjects arrive at the department at 800 AM Peripheral iv lines will be inserted into the antecubital veins of both forearms one for infusion of 51Cr-EDTA and hypertonic saline and one for withdrawal of blood samples The subjects will be kept in the supine position from 800 AM to 130 PM except during voiding which will take place in the sitting or standing position At 830 AM a priming dose of 51Cr-EDTA is administered followed by sustained infusion After 60 min of equilibration the study will continue with five clearance periods the first two of 30-min duration P1-P2 the last three of 60-min duration P3-P5 The first two clearance periods are baseline periods At 1030 AM 7 mlkg of 3 saline is given over 30 min Blood pressure and heart rate will be measured every 30 min from 930 AM to 130 PM Urine is collected in each clearance period and analyzed for sodium osmolality u-AQP2 u-ENaC-betaCR u-cAMP u-PGE2 and 51CrEDTA Blood samples will be drawn every 30 min from 930 AM to 1030 AM and every hour from 1130 AM to 130 PM and will be analyzed for sodium osmolality and 51Cr-EDTA In addition analysis of p-AVP p-Renin p-ANG II p-Aldo p-ANP and p-BNP will be performed from blood samples drawn at 1030 AM 1130 AM 1230 PM and 130 PM
Statistics Statistical analyses will be performed using SPSS version 15 SPSS Chicago IL Single baseline values are obtained by taking the weighted average of the measurements from the two baseline periods The baseline values of the two groups will be compared by Students t-test The baseline values during HS and LS intake will be compared by paired samples t-tests The investigators will use the General Linear Model Repeated Measures procedure in SPSS with time as the within-subject factor and group as the between-subject factor to compare the effect variables in patients and controls The changes in response to the hypertonic saline infusion in each group will be analyzed with the General Linear Model Repeated Measures procedure with time as the within-subject factor and paired samples t-tests with Bonferroni correction as post hoc tests P values 005 will be considered significant
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