End-stage Renal Disease (ESRD)Phase 4SAPDNCT01228279
Sympathetic Activity in Patients With End-stage Renal Disease on Peritoneal Dialysis
A Phase 4 study testing DIANEAL and EXTRANEAL in people with End-stage Renal Disease (ESRD) and Kidney Disease, run by Ottawa Hospital Research Institute at 1 site in Canada.
Trial summary
Hypothesis: Patients starting peritoneal dialysis with a glucose-based regimen have high sympathetic activity in response to an increase in leptin and insulin. Converting patients from a regimen of only glucose containing dialysate to a regimen with non-glucose-based solution, icodextrin, will reduce the insulin and… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- End-stage Renal Disease (ESRD), Kidney Disease
- What is being tested?
- DIANEAL and EXTRANEAL
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteCanada
- Study dates
- Jul 2007to Dec 2018
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult (age 18 years and older)
- Patients with end-stage renal disease(ESRD)/chronic kidney disease(CKD)stage 5
Who cannot join
- Diabetes Mellitus
- Acute coronary syndrome in the past 6 months
- Cardiac arrhythmias (2nd and 3rd degree heart block or premature ventricular complexes in Lown classes 4 or 5)
- Symptoms suggestive of obstructive or central sleep apnea (with a score of > 10 on Epworth sleepiness scale)
- Patients taking Clonidine
- Body mass index (BMI) > 34
Show all 16Show fewer
- Patients unable to give consent
- Pregnant women
- Patients with leg injury involving nerve damage
- Patients taking anticoagulant medication
- Patients with significant bleeding disorder or liver disorder
- Hemoglobin <1.05 g/dl at the time of initiation of therapy
- patients with unilateral or bilateral nephrectomy
- Planned kidney transplant in the next 4 months
- Life expectancy under 6 months
- Oliguria (urine output less than 400 ml per day)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effects of Non-Glucose-Based Peritoneal Dialysis Solution "EXTRANEAL" on Changes in Leptin Levels and Sympathetic Activity Induced by Conventional Glucose-Based Dialysate "DIANEAL" in Patients on Peritoneal Dialysis
Hypothesis:
Patients starting peritoneal dialysis with a glucose-based regimen have high sympathetic activity in response to an increase in leptin and insulin. Converting patients from a regimen of only glucose containing dialysate to a regimen with non-glucose-based solution, icodextrin, will reduce the insulin and leptin levels and will reverse dialysis-induced increases in sympathetic activity.
Read the detailed description
Cardiovascular mortality remains higher among patients treated with peritoneal dialysis as compared to patients treated with hemodialysis. Sympathetic hyperactivity is considered a significant emerging risk factor for cardiovascular mortality among patients with ESRD (End-Stage Renal Disease). Sympathetic activity, via its hemodynamic effects and trophic effects, and in interaction with RAAS (Renin Angiotensin Aldosterone System), does play a major role in cardiac and vascular remodelling, development of LVH and vascular hypertrophy, as well as progression to CHF. Glucose-based dialysate induces hyperinsulinemia and hyperleptinemia. We propose that hyperleptinemia induced by glucose-based peritoneal solution is a significant contributing factor to sympathetic hyperactivity in ESRD patients treated with PD, and could be prevented by non-glucose-based PD solution such as icodextrin-based.
Adult patients with ESRD starting PD as their first renal replacement therapy modality will be studied. Patients will be recruited 1-3 weeks prior to starting PD treatment. At baseline, specific studies for microneurography (MSNA), fasting plasma insulin, leptin, catecholamines and brain natriuretic peptide (BNP) will be performed. EKG will be recorded and digitized for further assessment of heart rate variability using power spectral analysis. Extracellular fluid volume status will be assessed by bioelectrical impedance. Central vascular volume will be assessed from inferior vena cava (IVC) by heart ultrasound. Consequently 24-h ambulatory blood pressure monitoring(ABPM)and a 24-h urine collection for urea clearance and creatinine clearance will be done.
All participants into the study will receive a PD treatment for 6 weeks with standard glucose-based PD solution Dianeal. The specific studies are repeated at 6 weeks.Then, patients will be randomized to one of the two groups (arms). One group will continue with Dianeal PD solution for another 12 weeks. The other group will receive Dianeal during the day and Extraneal, icodextrin or non-glucose based solution, during the night only, for the next 12 weeks. The specific studies are repeated at 12 weeks after randomization (18 weeks of PD treatment).
- Conditions
- End-stage Renal Disease (ESRD), Kidney Disease
- Being tested
- DIANEAL, EXTRANEAL
- Keywords
- Peritoneal Dialysis, Dialysis Solutions, Artificial Kidney, Renal Replacement Therapy, Renal Dialysis, Sympathetic Nervous System, Leptin, Icodextrin
- Medical subject headings
- Kidney Failure, Chronic, Kidney Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DIANEALOther
Also called Dextrose-based PD solution
Weeks 1 to 6 (6 weeks):
- CAPD (Continuous Ambulatory Peritoneal Dialysis)patients will receive three 4-6 hour dwells of DIANEAL during the day and one 8-10-hour dwell of DIANEAL during the night
- CCPD (Continuous Cycler Peritoneal Dialysis)patients will receive one-two 4-6 hour dwells of DIANEAL during the day and three to seven 2-4-hour dwells of DIANEAL during the night
Weeks 7 to 18 (12 weeks):
*same regimen as weeks 1 to 6, for both CAPD and CCPD patients
EXTRANEALOther
Also called Icodextrin-based PD solution
Weeks 1 to 6 (6 weeks):
- CAPD (Continuous Ambulatory Peritoneal Dialysis)patients will receive three 4-6 hour dwells of DIANEAL during the day and one 8-10-hour dwell of DIANEAL during the night
- CCPD (Continuous Cycler Peritoneal Dialysis)patients will receive one-two 8-12-hour dwells of DIANEAL during the day and three to seven 2-4-hour dwells of DIANEAL during the night
Weeks 7 to 18 (12 weeks):
- CAPD (Continuous Ambulatory Peritoneal Dialysis)patients will receive three 4-6 hour dwells of DIANEAL during the day and one 8-10-hour dwell of EXTRANEAL during the night
- CCPD (Continuous Cycler Peritoneal Dialysis)patients will receive one-two 8-12-hour dwells of DIANEAL during the day and one 8-12-hour dwell of EXTRANEAL during the night
| Study group | Role | What they receive |
|---|---|---|
| DIANEAL | Active comparator | One group of patients will start peritoneal dialysis with the glucose-based solution (DIANEAL) for 6 weeks, then will continue with the same type of solution for another 12 weeks. Receives: Other: DIANEAL |
| EXTRANEAL | Active comparator | The other group of patients will start peritoneal dialysis with the glucose-based solution (DIANEAL) for 6 weeks, then will continue with DIANEAL solution during the day and the non-glucose-based solution, EXTRANEAL, during the night Receives: Other: EXTRANEAL |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in muscle sympathetic nerve activity(MSNA)
Muscle sympathetic nerve activity(MSNA) is measured by microneurography at
- baseline (before starting peritoneal dialysis)
- 6 weeks of PD
- 18 weeks of PD(12 weeks after randomization)
MSNA increases on a glucose-based dialysis regimen and may decrease by adding non-glucose-based solution
Measured: 6 weeks on PD and 18 weeks on PD
Changes in leptin levels
Plasma leptin increases on a glucose-based peritoneal dialysis regimen and may decrease by adding non-glucose-based solution to the dialysis regimen
Measured: 6 weeks on PD and 18 weeks on PD
Secondary outcomes (7)
Changes in blood pressure as assessed from 24-hour ambulatory blood pressure monitor (ABPM)
Blood pressure will be assessed with 24-hour ABPM at baseline, 6 weeks on PD and 18 weeks after starting peritoneal dilaysis. Summary measures of each day and night period include average systolic and diastolic BP as well as % nocturnal dipping. These summary measures can predict cardiovascular events more accurately than casual BP measures
Measured: 6 weeks on PD and 18 weeks on PD
Changes in extracellular volume assessed by bioelectrical impedance (BIA)
Bioelectrical impedance directly measures extracellular fluid volume and total body water. The test is based on the ability to detect differences in the conductive properties of a cell by measuring its resistance (impedance) to electrical current. The technique is reliable for tracking sequential changes in extracellular fluid volume.
Measured: 6 weeks on PD and 18 weeks on PD
Changes in heart rate variability
During the microneurography testing, EKG is recorded. Heart rate and heart rate variability(HRV) will be analyzed from EKG data at baseline, 6 weeks and 18 weeks after starting dialysis.
Measured: 6 weeks on PD and 18 weeks on PD
Changes in central intravascular volume assessed by cardiac ultrasound
Central intravascular volume will be assessed by measuring inferior vena cava (IVC) diameter during cardiac ultrasound at baseline, 6 weeks and 18 weeks on dialysis treatment
Measured: 6 weeks on PD and 18 weeks on PD
Changes in plasma catecholamines levels
*Plasma catecholamines (epinephrine and norepinephrine) increase on a glucose-based peritoneal dialysis regimen and may decrease by adding non-glucose-based solution to the dialysis regimen
Measured: 6 weeks on PD and 18 weeks on PD
Changes in BNP (Brain Natriuretic Peptide)levels
*Brain Natriuretic Peptide (BNP)increases on a glucose-based peritoneal dialysis regimen and may decrease by adding non-glucose-based solution to the dialysis regimen
Measured: 6 weeks on PD and 18 weeks on PD
Changes in plasma insulin levels
*Plasma insulin increases on a glucose-based peritoneal dialysis regimen and may decrease by adding non-glucose-based solution to the dialysis regimen
Measured: 6 weeks on PD and 18 weeks on PD
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Oct 2010 (estimated)
- Study startJul 2007
- Primary completionDec 2018
- Study completionDec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for End-stage Renal Disease (ESRD)Studies of the same condition, open and under way.
- More trials run by Ottawa Hospital Research InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ottawa Hospital Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Heart and Stroke Foundation of Ontario
- Responsible party
- Principal investigator, Dr. Marcel Ruzicka, Ottawa Hospital Research Institute
- Investigators
- Marcel Ruzicka, MD, PhD, Principal investigator, Ottawa Hospital Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01228279
- Sponsor's protocol ID
- NA6951
- Acronym
- SAPD
- Status last verified
- Mar 2021
- First submitted
- 13 Oct 2010
- Last updated
- 15 Mar 2021
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Non-Glucose-Based Peritoneal Dialysis Solution "EXTRANEAL" on Changes in Leptin Levels and Sympathetic Activity Induced by Conventional Glucose-Based Dialysate "DIANEAL" in Patients on Peritoneal Dialysis
- ClinicalTrials.gov ID
- NCT01228279
- Acronym / sponsor ID
- SAPD / NA6951
- Conditions
- End-stage Renal Disease (ESRD), Kidney Disease
- Keywords
- Peritoneal Dialysis, Dialysis Solutions, Artificial Kidney, Renal Replacement Therapy, Renal Dialysis, Sympathetic Nervous System, Leptin, Icodextrin
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Ottawa Hospital Research InstituteUniversity, hospital or other
- Collaborators
- Heart and Stroke Foundation of Ontario
- Study start
- Jul 2007 (actual)
- Primary completion
- Dec 2018 (actual)
- Study completion
- Dec 2018 (actual)
- First posted
- 26 Oct 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Hypothesis:
Patients starting peritoneal dialysis with a glucose-based regimen have high sympathetic activity in response to an increase in leptin and insulin. Converting patients from a regimen of only glucose containing dialysate to a regimen with non-glucose-based solution, icodextrin, will reduce the insulin and leptin levels and will reverse dialysis-induced increases in sympathetic activity.
Detailed description
Cardiovascular mortality remains higher among patients treated with peritoneal dialysis as compared to patients treated with hemodialysis. Sympathetic hyperactivity is considered a significant emerging risk factor for cardiovascular mortality among patients with ESRD (End-Stage Renal Disease). Sympathetic activity, via its hemodynamic effects and trophic effects, and in interaction with RAAS (Renin Angiotensin Aldosterone System), does play a major role in cardiac and vascular remodelling, development of LVH and vascular hypertrophy, as well as progression to CHF. Glucose-based dialysate induces hyperinsulinemia and hyperleptinemia. We propose that hyperleptinemia induced by glucose-based peritoneal solution is a significant contributing factor to sympathetic hyperactivity in ESRD patients treated with PD, and could be prevented by non-glucose-based PD solution such as icodextrin-based.
Adult patients with ESRD starting PD as their first renal replacement therapy modality will be studied. Patients will be recruited 1-3 weeks prior to starting PD treatment. At baseline, specific studies for microneurography (MSNA), fasting plasma insulin, leptin, catecholamines and brain natriuretic peptide (BNP) will be performed. EKG will be recorded and digitized for further assessment of heart rate variability using power spectral analysis. Extracellular fluid volume status will be assessed by bioelectrical impedance. Central vascular volume will be assessed from inferior vena cava (IVC) by heart ultrasound. Consequently 24-h ambulatory blood pressure monitoring(ABPM)and a 24-h urine collection for urea clearance and creatinine clearance will be done.
All participants into the study will receive a PD treatment for 6 weeks with standard glucose-based PD solution Dianeal. The specific studies are repeated at 6 weeks.Then, patients will be randomized to one of the two groups (arms). One group will continue with Dianeal PD solution for another 12 weeks. The other group will receive Dianeal during the day and Extraneal, icodextrin or non-glucose based solution, during the night only, for the next 12 weeks. The specific studies are repeated at 12 weeks after randomization (18 weeks of PD treatment).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| DIANEAL | Active comparator | Other: DIANEALOne group of patients will start peritoneal dialysis with the glucose-based solution (DIANEAL) for 6 weeks, then will continue with the same type of solution for another 12 weeks. |
| EXTRANEAL | Active comparator | Other: EXTRANEALThe other group of patients will start peritoneal dialysis with the glucose-based solution (DIANEAL) for 6 weeks, then will continue with DIANEAL solution during the day and the non-glucose-based solution, EXTRANEAL, during the night |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Adult (age 18 years and older)
- Patients with end-stage renal disease(ESRD)/chronic kidney disease(CKD)stage 5
Key exclusion criteria (16 listed)
- Diabetes Mellitus
- Acute coronary syndrome in the past 6 months
- Cardiac arrhythmias (2nd and 3rd degree heart block or premature ventricular complexes in Lown classes 4 or 5)
- Symptoms suggestive of obstructive or central sleep apnea (with a score of > 10 on Epworth sleepiness scale)
- Patients taking Clonidine
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DIANEALAlso: Dextrose-based PD solutionWeeks 1 to 6 (6 weeks): * CAPD (Continuous Ambulatory Peritoneal Dialysis)patients will receive three 4-6 hour dwells of DIANEAL during the day and one 8-10-hour dwell of DIANEAL during the night * CCPD (Continuous Cycler Peritoneal Dialysis)patients will receive one-two 4-6 hour dwells of DIANEAL during the day and three to seven 2-4-hour dwells of DIANEAL during the night Weeks 7 to 18 (12 weeks): *same regimen as weeks 1 to 6, for both CAPD and CCPD patients | Other | DIANEAL |
| EXTRANEALAlso: Icodextrin-based PD solutionWeeks 1 to 6 (6 weeks): * CAPD (Continuous Ambulatory Peritoneal Dialysis)patients will receive three 4-6 hour dwells of DIANEAL during the day and one 8-10-hour dwell of DIANEAL during the night * CCPD (Continuous Cycler Peritoneal Dialysis)patients will receive one-two 8-12-hour dwells of DIANEAL during the day and three to seven 2-4-hour dwells of DIANEAL during the night Weeks 7 to 18 (12 weeks): * CAPD (Continuous Ambulatory Peritoneal Dialysis)patients will receive three 4-6 hour dwells of DIANEAL during the day and one 8-10-hour dwell of EXTRANEAL during the night * CCPD (Continuous Cycler Peritoneal Dialysis)patients will receive one-two 8-12-hour dwells of DIANEAL during the day and one 8-12-hour dwell of EXTRANEAL during the night | Other | EXTRANEAL |
Primary outcome
Changes in muscle sympathetic nerve activity(MSNA)
Time frame: 6 weeks on PD and 18 weeks on PD
Muscle sympathetic nerve activity(MSNA) is measured by microneurography at * baseline (before starting peritoneal dialysis) * 6 weeks of PD * 18 weeks of PD(12 weeks after randomization) MSNA increases on a glucose-based dialysis regimen and may decrease by adding non-glucose-based solution
Changes in leptin levels
Time frame: 6 weeks on PD and 18 weeks on PD
Plasma leptin increases on a glucose-based peritoneal dialysis regimen and may decrease by adding non-glucose-based solution to the dialysis regimen
7 secondary outcomes
Changes in blood pressure as assessed from 24-hour ambulatory blood pressure monitor (ABPM)
Time frame: 6 weeks on PD and 18 weeks on PD
Changes in extracellular volume assessed by bioelectrical impedance (BIA)
Time frame: 6 weeks on PD and 18 weeks on PD
Changes in heart rate variability
Time frame: 6 weeks on PD and 18 weeks on PD
Changes in central intravascular volume assessed by cardiac ultrasound
Time frame: 6 weeks on PD and 18 weeks on PD
Changes in plasma catecholamines levels
Time frame: 6 weeks on PD and 18 weeks on PD
Changes in BNP (Brain Natriuretic Peptide)levels
Time frame: 6 weeks on PD and 18 weeks on PD
Changes in plasma insulin levels
Time frame: 6 weeks on PD and 18 weeks on PD
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Mar 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marcel Ruzicka, MD, PhD principal investigator
Ottawa Hospital Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing DIANEAL and EXTRANEAL in people with End-stage Renal Disease (ESRD) and Kidney Disease, run by Ottawa Hospital Research Institute at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in muscle sympathetic nerve activity(MSNA) (time frame: 6 weeks on PD and 18 weeks on PD). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Mar 2021.