End Stage Renal DiseaseNCT00759967
Conventional Hemodialysis vs. Short Daily Hemodialysis (6 Days / Week) and Mechanisms of Blood Pressure Control
A study testing Microneurography and Bioimpedance testing in people with End Stage Renal Disease, run by Ottawa Hospital Research Institute at 1 site in Canada.
Trial summary
More than 80% of patients with end stage renal disease have hypertension; 70% of whom are poorly controlled using conventional Hemodialysis therapy. An expanded extracellular fluid volume and an increase in peripheral vascular resistance as a result of hemodynamic/trophic effects of an increased sympathetic nerve… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- End Stage Renal Disease
- What is being tested?
- Microneurography and Bioimpedance testing
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteCanada
- Study dates
- Sep 2007to Jun 2012
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Systolic Hypertension
- They are able to make the time commitment for daily therapy
- They are capable of giving informed consent.
Who cannot join
- They are expected to receive a transplant within the next 12 months
- If they are considering a switch to peritoneal dialysis
- They are not expected to survive 12 months
- They have infections that require isolation (Vancomycin Resistant Enterococcus, Methicillin Resistant Staphylococcus Aureus, Hepatitis B)
- They have known symptomatic dilated cardiomyopathy (New York Association Class II or III with left ventricle ejection fraction of \<0.35
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Randomized Cross-over Study of Short Daily Hemodialysis Compared to Conventional Hemodialysis to Determine the Mechanisms of Hypertension Control
More than 80% of patients with end stage renal disease have hypertension; 70% of whom are poorly controlled using conventional Hemodialysis therapy. An expanded extracellular fluid volume and an increase in peripheral vascular resistance as a result of hemodynamic/trophic effects of an increased sympathetic nerve activity, angiotensin II, asymmetrical dimethyl arginine, and decreased nitric oxide are the most frequently quoted mechanisms contributing to hypertension in this population. The intermittent nature of conventional hemodialysis treatments (4 hours, 3 days/week) results in the majority of patients having a sustained expansion of the extracellular fluid volume that likely contributes to the activation of neurohormonal pathways. However, daily therapy including short daily hemodialysis (2 hours, 6 days/week) and nocturnal hemodialysis (6-8 hours, 5-6 days/week) improve or even normalize blood pressure. Short daily hemodialysis appears to improve blood pressure secondary to a reduction in extracellular fluid volume (7,8) whereas the improvement in blood pressure with nocturnal hemodialysis occurs by a reduction in peripheral vascular resistance (8,9,10). This is consistent with the Katzarski et al experience (7-8 hours, 3 days/week) and one randomized controlled trial in which blood pressure control was due to normalization of extracellular fluid volume in some patients and a reduction in peripheral vascular resistance in others. The majority of the studies in daily dialysis are observational, do not include a run-in period to optimize blood pressure management and have not explored the mechanisms of improvement in blood pressure in detail. We have designed a 9 month study to determine if the mechanism by which short daily hemodialysis is associated with an improvement in blood pressure control is secondary to changes in sympathetic nervous system activity and/ or extracellular fluid volume. Additionally we would like to explore the potential impact of short daily dialysis, compared to conventional dialysis, on markers of inflammation and oxidative stress in detail.
Read the detailed description
Patients with end stage renal disease have an adjusted risk of cardiovascular mortality that is 10-20 times greater than the general population. Of the modifiable risk factors, hypertension occurs in 80% of patients with end stage renal disease and is poorly controlled in 70% of patients. In several observational studies of daily hemodialysis, blood pressure has improved despite a reduction in the number of antihypertensive medications. A randomized crossover study in short daily hemodialysis also showed an improvement in systolic blood pressure and a reduction in left ventricular mass index. In limited investigation, the mechanism(s) responsible for the improvement in blood pressure have been attributed to a reduction in extracellular fluid volume (short daily) and a reduction in peripheral vascular resistance (nocturnal hemodialysis). The studies to date have been limited by failing to include a run in phase to optimize extracellular fluid volume prior to the initiation of daily dialysis. Additionally, only one study used a standardized algorithm for the management of blood pressure which is vital as the treatments are not blinded. We have designed a randomized, unblinded, 9 month cross-over study to determine the mechanism of blood pressure control on patients receiving conventional (3 times /week) HD to short daily HD (6 times /week 2 hrs/tx). After completing a 3 month run-in phase on conventional HD in which patient's dry weight and antihypertensive medications will be adjusted using a standardized algorithm, patients are to be randomized to a 3 month cross-over of daily HD versus conventional HD. The mechanism of improved blood pressure control will be explored using bioelectrical impedance to measure extracellular fluid volume (ECFV) and muscle sympathetic nerve activity (MSNA) as well as plasma catecholamines to measure the activity of the sympathetic nervous system. Additionally the effect of short daily HD, compared to conventional HD, on reactive oxygen species and markers of inflammation will be examined in Dr. Rhian Touyz lab. Lastly we will determine the patient's treatment preference.
- Conditions
- End Stage Renal Disease
- Being tested
- Microneurography, Bioimpedance testing
- Keywords
- Randomized, Cross-Over, Conventional, Daily, Hemodialysis
- Medical subject headings
- Kidney Failure, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MicroneurographyProcedure or surgery
Also called Catecholamines
Muscle sympathetic nerve activity measurement will be obtained using microneurography. Approximately 10-20% of microneurography recordings are not interpretable due to technical problems. For this reason, blood samples will be collected at the same time that the microneurography is to be done. These test will be done at 3 time points throughout the study.
Bioimpedance testingProcedure or surgery
Also called Bioimpedance, extracellular fluid volume measurement
bioimpedance measurement of extracellular fluid volume will be measured at the end of each 3 month period. This test will be done at 3 time points throughout the study.
| Study group | Role | What they receive |
|---|---|---|
| Short daily hemodialysis | Active comparator | After a 3 month run-in period patients who are randomized to this arm will receive 3 months of short daily hemodialysis(2 hours/day,6 days/week)B/P will be monitored according to the Canadian hypertension guidelines both pre and post each dialysis session. Antihypertensive medication will be adjusted accordingly to maintain BP within the guidelines.At the end of this 3 month period extracellular fluid volume (bioimpedance) will be measured using bioimpedance as well as sympathetic nerve activity using microneurography. Additionally Catecholamines as well as markers of oxidative stress will be collected. Receives: Procedure: Microneurography; Procedure: Bioimpedance testing |
| Conventional hemodialysis | Active comparator | After a 3 month run-in period patients who are randomized to this arm will receive 3 months of conventional hemodialysis 3 days/week 3.5-4 hours/ treatment. BP will be monitored according to the Canadian hypertension guidelines both pre and post each dialysis session. Antihypertensive medication will be adjusted accordingly to maintain BP within the guidelines.At the end of this 3 moth period extracellular fluid volume (bioimpedance) will be measured using bioimpedance as well as sympathetic nerve activity using microneurography. Additionally Catecholamines as well as markers of oxidative stress will be collected. Receives: Procedure: Microneurography; Procedure: Bioimpedance testing |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean Systolic Blood Pressure Over the Third Month of Each Treatment Arm
The average of 2 measurements taken pre each dialysis session in the third month of treatment were compared when the patients were on conventional hemodialysis compared to short daily hemodialysis. SBP was taken in accordance with guidelines from the Canadian Hypertension Society
Measured: Average of the last month of the 3 month intervention
Secondary outcomes (5)
To Determine if the Mechanism by Which Short Daily Hemodialysis is Associated With Changes in Extracellular Fluid Volume
The extracellular fluid volume will be measured using bioelectrical impedance to determine if the mechanism by which short daily hemodialysis is associated with an improvement in blood pressure control is secondary to changes in extracellular fluid volume.
Measured: once the final participant has completed all intervention procedures, approx. 3 months
To Determine if Short Daily Hemodialysis, Compared to Conventional Hemodialysis Maintains Metabolic Homeostasis
Serum phosphate values from the end of the three month run in phase and after randomization used to measure metabolic homeostasis
Measured: once the last participant has completed run in phase and after randomization, approx. 3 months
To Determine if the Enhance Control of Blood Pressure With Daily Hemodialysis Compare to Conventional Hemodialysis is Associated With a Reduction in Oxidative Stress.
Measured: once the final participant has completed all intervention procedures, approx. 3 months
To Determine Patient Modality Preference.
each participant will complete a questionaire regarding modality preference
Measured: at study completion
To Determine if the Enhance Control of Blood Pressure With Daily Hemodialysis Compare to Conventional Hemodialysis is Associated With a Reduction in Markers of Inflammation
Measured: once the final participant has completed all intervention procedures, approx. 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2008 (estimated)
- Study startSep 2007
- Primary completionJun 2011
- Study completionJun 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for End Stage Renal DiseaseStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ottawa Hospital Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Heart and Stroke Foundation of Ontario, University of Ottawa
- Responsible party
- Sponsor
- Investigators
- Deborah Zimmerman, MD, Principal investigator, Ottawa Hospital Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00759967
- Sponsor's protocol ID
- 2006 77401H
- Status last verified
- Jan 2017
- First submitted
- 24 Sep 2008
- Last updated
- 4 Aug 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Zimmerman DL, Ruzicka M, Hebert P, Fergusson D, Touyz RM, Burns KD. Short daily versus conventional hemodialysis for hypertensive patients: a randomized cross-over study. PLoS One. 2014 May 29;9(5):e97135. doi: 10.1371/journal.pone.0097135. eCollection 2014.
PubMed 24875804
Study at a glance
From the registry record, last updated by the sponsor on 4 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Cross-over Study of Short Daily Hemodialysis Compared to Conventional Hemodialysis to Determine the Mechanisms of Hypertension Control
- ClinicalTrials.gov ID
- NCT00759967
- Acronym / sponsor ID
- 2006 77401H
- Conditions
- End Stage Renal Disease
- Keywords
- Randomized, Cross-Over, Conventional, Daily, Hemodialysis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Ottawa Hospital Research InstituteUniversity, hospital or other
- Collaborators
- Heart and Stroke Foundation of Ontario, University of Ottawa
- Study start
- Sep 2007
- Primary completion
- Jun 2011 (actual)
- Study completion
- Jun 2012 (actual)
- First posted
- 25 Sep 2008 (estimated)
- Results
- Posted 4 Aug 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
More than 80% of patients with end stage renal disease have hypertension; 70% of whom are poorly controlled using conventional Hemodialysis therapy. An expanded extracellular fluid volume and an increase in peripheral vascular resistance as a result of hemodynamic/trophic effects of an increased sympathetic nerve activity, angiotensin II, asymmetrical dimethyl arginine, and decreased nitric oxide are the most frequently quoted mechanisms contributing to hypertension in this population. The intermittent nature of conventional hemodialysis treatments (4 hours, 3 days/week) results in the majority of patients having a sustained expansion of the extracellular fluid volume that likely contributes to the activation of neurohormonal pathways. However, daily therapy including short daily hemodialysis (2 hours, 6 days/week) and nocturnal hemodialysis (6-8 hours, 5-6 days/week) improve or even normalize blood pressure. Short daily hemodialysis appears to improve blood pressure secondary to a reduction in extracellular fluid volume (7,8) whereas the improvement in blood pressure with nocturnal hemodialysis occurs by a reduction in peripheral vascular resistance (8,9,10). This is consistent with the Katzarski et al experience (7-8 hours, 3 days/week) and one randomized controlled trial in which blood pressure control was due to normalization of extracellular fluid volume in some patients and a reduction in peripheral vascular resistance in others. The majority of the studies in daily dialysis are observational, do not include a run-in period to optimize blood pressure management and have not explored the mechanisms of improvement in blood pressure in detail. We have designed a 9 month study to determine if the mechanism by which short daily hemodialysis is associated with an improvement in blood pressure control is secondary to changes in sympathetic nervous system activity and/ or extracellular fluid volume. Additionally we would like to explore the potential impact of short daily dialysis, compared to conventional dialysis, on markers of inflammation and oxidative stress in detail.
Detailed description
Patients with end stage renal disease have an adjusted risk of cardiovascular mortality that is 10-20 times greater than the general population. Of the modifiable risk factors, hypertension occurs in 80% of patients with end stage renal disease and is poorly controlled in 70% of patients. In several observational studies of daily hemodialysis, blood pressure has improved despite a reduction in the number of antihypertensive medications. A randomized crossover study in short daily hemodialysis also showed an improvement in systolic blood pressure and a reduction in left ventricular mass index. In limited investigation, the mechanism(s) responsible for the improvement in blood pressure have been attributed to a reduction in extracellular fluid volume (short daily) and a reduction in peripheral vascular resistance (nocturnal hemodialysis). The studies to date have been limited by failing to include a run in phase to optimize extracellular fluid volume prior to the initiation of daily dialysis. Additionally, only one study used a standardized algorithm for the management of blood pressure which is vital as the treatments are not blinded. We have designed a randomized, unblinded, 9 month cross-over study to determine the mechanism of blood pressure control on patients receiving conventional (3 times /week) HD to short daily HD (6 times /week 2 hrs/tx). After completing a 3 month run-in phase on conventional HD in which patient's dry weight and antihypertensive medications will be adjusted using a standardized algorithm, patients are to be randomized to a 3 month cross-over of daily HD versus conventional HD. The mechanism of improved blood pressure control will be explored using bioelectrical impedance to measure extracellular fluid volume (ECFV) and muscle sympathetic nerve activity (MSNA) as well as plasma catecholamines to measure the activity of the sympathetic nervous system. Additionally the effect of short daily HD, compared to conventional HD, on reactive oxygen species and markers of inflammation will be examined in Dr. Rhian Touyz lab. Lastly we will determine the patient's treatment preference.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Short daily hemodialysis | Active comparator | Procedure: Microneurography, Procedure: Bioimpedance testingAfter a 3 month run-in period patients who are randomized to this arm will receive 3 months of short daily hemodialysis(2 hours/day,6 days/week)B/P will be monitored according to the Canadian hypertension guidelines both pre and post each dialysis session. Antihypertensive medication will be adjusted accordingly to maintain BP within the guidelines.At the end of this 3 month period extracellular fluid volume (bioimpedance) will be measured using bioimpedance as well as sympathetic nerve activity using microneurography. Additionally Catecholamines as well as markers of oxidative stress will be collected. |
| Conventional hemodialysis | Active comparator | Procedure: Microneurography, Procedure: Bioimpedance testingAfter a 3 month run-in period patients who are randomized to this arm will receive 3 months of conventional hemodialysis 3 days/week 3.5-4 hours/ treatment. BP will be monitored according to the Canadian hypertension guidelines both pre and post each dialysis session. Antihypertensive medication will be adjusted accordingly to maintain BP within the guidelines.At the end of this 3 moth period extracellular fluid volume (bioimpedance) will be measured using bioimpedance as well as sympathetic nerve activity using microneurography. Additionally Catecholamines as well as markers of oxidative stress will be collected. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Systolic Hypertension
- They are able to make the time commitment for daily therapy
- They are capable of giving informed consent.
Key exclusion criteria (5 listed)
- They are expected to receive a transplant within the next 12 months
- If they are considering a switch to peritoneal dialysis
- They are not expected to survive 12 months
- They have infections that require isolation (Vancomycin Resistant Enterococcus, Methicillin Resistant Staphylococcus Aureus, Hepatitis B)
- They have known symptomatic dilated cardiomyopathy (New York Association Class II or III with left ventricle ejection fraction of \<0.35
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 |
|---|---|---|
| MicroneurographyAlso: CatecholaminesMuscle sympathetic nerve activity measurement will be obtained using microneurography. Approximately 10-20% of microneurography recordings are not interpretable due to technical problems. For this reason, blood samples will be collected at the same time that the microneurography is to be done. These test will be done at 3 time points throughout the study. | Procedure or surgery | Conventional hemodialysis, Short daily hemodialysis |
| Bioimpedance testingAlso: Bioimpedance, extracellular fluid volume measurementbioimpedance measurement of extracellular fluid volume will be measured at the end of each 3 month period. This test will be done at 3 time points throughout the study. | Procedure or surgery | Conventional hemodialysis, Short daily hemodialysis |
Primary outcome
Mean Systolic Blood Pressure Over the Third Month of Each Treatment Arm
Time frame: Average of the last month of the 3 month intervention
The average of 2 measurements taken pre each dialysis session in the third month of treatment were compared when the patients were on conventional hemodialysis compared to short daily hemodialysis. SBP was taken in accordance with guidelines from the Canadian Hypertension Society
5 secondary outcomes
To Determine if the Mechanism by Which Short Daily Hemodialysis is Associated With Changes in Extracellular Fluid Volume
Time frame: once the final participant has completed all intervention procedures, approx. 3 months
To Determine if Short Daily Hemodialysis, Compared to Conventional Hemodialysis Maintains Metabolic Homeostasis
Time frame: once the last participant has completed run in phase and after randomization, approx. 3 months
To Determine if the Enhance Control of Blood Pressure With Daily Hemodialysis Compare to Conventional Hemodialysis is Associated With a Reduction in Oxidative Stress.
Time frame: once the final participant has completed all intervention procedures, approx. 3 months
To Determine Patient Modality Preference.
Time frame: at study completion
To Determine if the Enhance Control of Blood Pressure With Daily Hemodialysis Compare to Conventional Hemodialysis is Associated With a Reduction in Markers of Inflammation
Time frame: once the final participant has completed all intervention procedures, approx. 3 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Aug 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 24875804Zimmerman DL, Ruzicka M, Hebert P, Fergusson D, Touyz RM, Burns KD. Short daily versus conventional hemodialysis for hypertensive patients: a randomized cross-over study. PLoS One. 2014 May 29;9(5):e97135. doi: 10.1371/journal.pone.0097135. eCollection 2014.
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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.
Deborah Zimmerman, MD 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 study testing Microneurography and Bioimpedance testing in people with End Stage Renal 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 3 inclusion and 5 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 4 Aug 2017. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Aug 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Mean Systolic Blood Pressure Over the Third Month of Each Treatment Arm (time frame: Average of the last month of the 3 month intervention). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00759967, which also lists 1 linked publication.
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 4 Aug 2017.