End-Stage Renal DiseaseACUMEN-HDNCT02393222
Assessing Cognitive fUnction and MEasuring the Cerebral circulatioN on HaemoDialysis
An observational study of End-Stage Renal Disease and Stroke, run by NHS Greater Glasgow and Clyde.
Trial summary
Stroke disease and cognitive impairment are common in patients established on haemodialysis (HD) for end-stage renal disease (ESRD). Further, initiation of HD appears to transiently increase the risk of stroke. The mechanism by which this occurs is not known. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- End-Stage Renal Disease, Stroke, Cognition Disorders
- What is being tested?
- Observing effect of routine HD
- How many people
- 97 participants
- Where
- No sites listed yet
- Study dates
- Mar 2015to Aug 2017
- Phase
- Observational
- 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 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: All adult patients receiving haemodialysis for end-stage renal disease.
Who may be able to join
- Adult patients treated with HD at the Glasgow Renal Unit and its satellite units
Who cannot join
- Planned live donor transplant is planned during the next 6 months
- Predicted life expectancy <6 months
- Inability to give informed consent
- Contraindications to MRI imaging (pacemaker, extreme claustrophobia),
- Known clinical or radiological diagnoses of cerebrovascular disease
- Severe cognitive impairment (MOCA <17)
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Exploring the Natural History of Cerebrovascular Disease in Patients With End-stage Renal Disease on Haemodialysis
Stroke disease and cognitive impairment are common in patients established on haemodialysis (HD) for end-stage renal disease (ESRD). Further, initiation of HD appears to transiently increase the risk of stroke. The mechanism by which this occurs is not known.
Using ultrasound, patient questionnaires and brain MRI our study will observe changes in cognition and cerebral blood flow whilst receiving HD compared to a non-dialysis day. Transient clinical and ultrasound alterations will be correlated to radiographic changes in cerebral perfusion and structure on MRI to determine the underlying mechanism for the increased stroke risk. The investigators will observe this effect in the immediate and longer term (12 months observation).
A greater understanding will allow development of effective preventive strategies.
Read the detailed description
Stroke is common in the United Kingdom and a leading cause of adult disability. It has been reported that more than half of all stroke survivors remain dependent on carers for everyday activities. A greater understanding stroke disease has led to improvements in stroke care for the general population.
Patients with ESRD are at increased risk of cerebrovascular disease with a risk approximately 5-10 times higher than the general population yet a relative paucity of data exploring the mechanisms and impact of stroke disease on patients on HD remains. Signs of cerebrovascular disease are common with evidence of early stroke disease (white matter hyperintensities on MRI) having been described in up to 50% of ESRD patients. In addition to this it is now estimated that up to 70% of patients on dialysis aged 55 years and older have moderate to severe cognitive impairment. Previous work has revealed that cognition declines during dialysis - specifically a decrease in executive function has been reported, without significant memory impairment. Such findings are in suggestive of vascular related injury. Mean cerebral blood flow assessed by transcranial Doppler ultrasound is reduced during dialysis, although whether this finding is associated with a clinical outcome is not clear.
In order to generate appropriate preventive strategies for stroke in ESRD the mechanism by which injury occurs must be confirmed. In addition, although a decrease in executive function has been shown during HD it is unclear if long-term HD is associated with progressive decline or if this clinical finding correlates with neuroimaging.
This study is being performed to determine:
- The impact of long term HD (including indices of cardiovascular instability) on changes on brain MRI and cognitive function.
- The relationship between intracerebral blood flow rate, brain MRI findings and neurocognitive function
- The relationship between intracranial blood flow measures (during and post haemodialysis (HD)) and brain perfusion and structure
Following informed written consent patients will be observed over a 12 month period. On the first visit participants will undergo a transcranial ultrasound before and during HD to achieve baseline and intra-dialytic blood flow velocities. During the dialysis sessions a neurocognitive assessment (patient questionnaire) will be performed which will assess multiple cognitive domains. On completion of dialysis a subgroup will undergo a brain MRI. All patients will meet with the investigators within 2 weeks to repeat the neurocognitive assessment on a non-dialysis day. This will allow for comparison of cognitive changes, alterations in cerebral blood flow and (in some) correlation with MRI findings. All participants will repeat this process 12 months later.
- Conditions
- End-Stage Renal Disease, Stroke, Cognition Disorders
- Being tested
- Observing effect of routine HD
- Keywords
- Dialysis, Cerebrovascular disease, ESRD
- Medical subject headings
- Kidney Failure, Chronic, Stroke, Cognition Disorders, Cerebrovascular Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Observing effect of routine HDOther
Observing effect of routine HD via transcranial doppler, neurocognitive questionnaires and (in some) brain MRI
| Study group | Role | What they receive |
|---|---|---|
| Patients with ESRD on HD | Adult patients with ESRD on HD. Observing the effect of a single HD session on cerebral blood flow (assessed by transcranial doppler) and cognitive function (assessed by neurocognitive questionnaires). Subgroup to undergo brain MRI. Receives: Other: Observing effect of routine HD |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression of white matter hyperintensities on MRI
Use of visual rating scales to quantify white matter burden at time 0 and 12 months
Measured: 12 months
Secondary outcomes (3)
Correlation between alterations in cerebral blood flow and cognition
Statistical correlation determined between a decreased in cerebral blood flow (as measured on transcranial doppler) and reduction in cognitive scores on assessment
Measured: Within 4 hour treatment period (of HD)
Correlation between alterations in cerebral blood flow and white matter hyperintensity burden progression
Statistical correlation between reductions in cerebral bloe
Measured: 12 months
Evidence of transient cognitive impairment during HD
Use of multi-domain neurocognitive battery to assess cognition during HD. Baseline cognition will be assessed on a non-dialysis day.
Measured: Within 2 weeks (direct comparison of cognition during dialysis and on non-dialysis day)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2015 (estimated)
- Study startMar 2015
- Primary completionAug 2016 (estimated)
- Study completionAug 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for End-Stage Renal DiseaseStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 97 participants (estimated)
Sponsor and investigators
- Lead sponsor
- NHS Greater Glasgow and Clyde
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mark D Findlay, MBChB, Principal investigator, University of Glasgow
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02393222
- Sponsor's protocol ID
- GN14RE639
- Acronym
- ACUMEN-HD
- Status last verified
- Mar 2015
- First submitted
- 26 Feb 2015
- Last updated
- 19 Mar 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Sozio SM, Armstrong PA, Coresh J, Jaar BG, Fink NE, Plantinga LC, Powe NR, Parekh RS. Cerebrovascular disease incidence, characteristics, and outcomes in patients initiating dialysis: the choices for healthy outcomes in caring for ESRD (CHOICE) study. Am J Kidney Dis. 2009 Sep;54(3):468-77. doi: 10.1053/j.ajkd.2009.01.261. Epub 2009 Apr 19.
PubMed 19376618Naganuma T, Takemoto Y, Shoji T, Shima H, Ishimura E, Okamura M, Nakatani T. Factors associated with cerebral white matter hyperintensities in haemodialysis patients. Nephrology (Carlton). 2012 Aug;17(6):561-8. doi: 10.1111/j.1440-1797.2012.01596.x.
PubMed 22429518Murray AM, Tupper DE, Knopman DS, Gilbertson DT, Pederson SL, Li S, Smith GE, Hochhalter AK, Collins AJ, Kane RL. Cognitive impairment in hemodialysis patients is common. Neurology. 2006 Jul 25;67(2):216-23. doi: 10.1212/01.wnl.0000225182.15532.40.
PubMed 16864811Sarnak MJ, Tighiouart H, Scott TM, Lou KV, Sorensen EP, Giang LM, Drew DA, Shaffi K, Strom JA, Singh AK, Weiner DE. Frequency of and risk factors for poor cognitive performance in hemodialysis patients. Neurology. 2013 Jan 29;80(5):471-80. doi: 10.1212/WNL.0b013e31827f0f7f. Epub 2013 Jan 9.
PubMed 23303848Skinner H, Mackaness C, Bedforth N, Mahajan R. Cerebral haemodynamics in patients with chronic renal failure: effects of haemodialysis. Br J Anaesth. 2005 Feb;94(2):203-5. doi: 10.1093/bja/aei016. Epub 2004 Nov 5.
PubMed 15531623Murray AM, Seliger S, Lakshminarayan K, Herzog CA, Solid CA. Incidence of stroke before and after dialysis initiation in older patients. J Am Soc Nephrol. 2013 Jun;24(7):1166-73. doi: 10.1681/ASN.2012080841. Epub 2013 Apr 25.
PubMed 23620399
Study at a glance
From the registry record, last updated by the sponsor on 19 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Exploring the Natural History of Cerebrovascular Disease in Patients With End-stage Renal Disease on Haemodialysis
- ClinicalTrials.gov ID
- NCT02393222
- Acronym / sponsor ID
- ACUMEN-HD / GN14RE639
- Conditions
- End-Stage Renal Disease, Stroke, Cognition Disorders
- Keywords
- Dialysis, Cerebrovascular disease, ESRD
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 97 participants (estimated)
- Lead sponsor
- NHS Greater Glasgow and ClydeUniversity, hospital or other
- Study start
- Mar 2015
- Primary completion
- Aug 2016 (estimated)
- Study completion
- Aug 2017 (estimated)
- First posted
- 19 Mar 2015 (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.
Stroke disease and cognitive impairment are common in patients established on haemodialysis (HD) for end-stage renal disease (ESRD). Further, initiation of HD appears to transiently increase the risk of stroke. The mechanism by which this occurs is not known.
Using ultrasound, patient questionnaires and brain MRI our study will observe changes in cognition and cerebral blood flow whilst receiving HD compared to a non-dialysis day. Transient clinical and ultrasound alterations will be correlated to radiographic changes in cerebral perfusion and structure on MRI to determine the underlying mechanism for the increased stroke risk. The investigators will observe this effect in the immediate and longer term (12 months observation).
A greater understanding will allow development of effective preventive strategies.
Detailed description
Stroke is common in the United Kingdom and a leading cause of adult disability. It has been reported that more than half of all stroke survivors remain dependent on carers for everyday activities. A greater understanding stroke disease has led to improvements in stroke care for the general population.
Patients with ESRD are at increased risk of cerebrovascular disease with a risk approximately 5-10 times higher than the general population yet a relative paucity of data exploring the mechanisms and impact of stroke disease on patients on HD remains. Signs of cerebrovascular disease are common with evidence of early stroke disease (white matter hyperintensities on MRI) having been described in up to 50% of ESRD patients. In addition to this it is now estimated that up to 70% of patients on dialysis aged 55 years and older have moderate to severe cognitive impairment. Previous work has revealed that cognition declines during dialysis - specifically a decrease in executive function has been reported, without significant memory impairment. Such findings are in suggestive of vascular related injury. Mean cerebral blood flow assessed by transcranial Doppler ultrasound is reduced during dialysis, although whether this finding is associated with a clinical outcome is not clear.
In order to generate appropriate preventive strategies for stroke in ESRD the mechanism by which injury occurs must be confirmed. In addition, although a decrease in executive function has been shown during HD it is unclear if long-term HD is associated with progressive decline or if this clinical finding correlates with neuroimaging.
This study is being performed to determine:
- The impact of long term HD (including indices of cardiovascular instability) on changes on brain MRI and cognitive function.
- The relationship between intracerebral blood flow rate, brain MRI findings and neurocognitive function
- The relationship between intracranial blood flow measures (during and post haemodialysis (HD)) and brain perfusion and structure
Following informed written consent patients will be observed over a 12 month period. On the first visit participants will undergo a transcranial ultrasound before and during HD to achieve baseline and intra-dialytic blood flow velocities. During the dialysis sessions a neurocognitive assessment (patient questionnaire) will be performed which will assess multiple cognitive domains. On completion of dialysis a subgroup will undergo a brain MRI. All patients will meet with the investigators within 2 weeks to repeat the neurocognitive assessment on a non-dialysis day. This will allow for comparison of cognitive changes, alterations in cerebral blood flow and (in some) correlation with MRI findings. All participants will repeat this process 12 months later.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients with ESRD on HD | – | Other: Observing effect of routine HDAdult patients with ESRD on HD. Observing the effect of a single HD session on cerebral blood flow (assessed by transcranial doppler) and cognitive function (assessed by neurocognitive questionnaires). Subgroup to undergo brain MRI. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- All adult patients receiving haemodialysis for end-stage renal disease.
Key inclusion criteria (1 listed)
- Adult patients treated with HD at the Glasgow Renal Unit and its satellite units
Key exclusion criteria (6 listed)
- Planned live donor transplant is planned during the next 6 months
- Predicted life expectancy <6 months
- Inability to give informed consent
- Contraindications to MRI imaging (pacemaker, extreme claustrophobia),
- Known clinical or radiological diagnoses of cerebrovascular disease
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 |
|---|---|---|
| Observing effect of routine HDObserving effect of routine HD via transcranial doppler, neurocognitive questionnaires and (in some) brain MRI | Other | Patients with ESRD on HD |
Primary outcome
Progression of white matter hyperintensities on MRI
Time frame: 12 months
Use of visual rating scales to quantify white matter burden at time 0 and 12 months
3 secondary outcomes
Correlation between alterations in cerebral blood flow and cognition
Time frame: Within 4 hour treatment period (of HD)
Correlation between alterations in cerebral blood flow and white matter hyperintensity burden progression
Time frame: 12 months
Evidence of transient cognitive impairment during HD
Time frame: Within 2 weeks (direct comparison of cognition during dialysis and on non-dialysis day)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Mar 2015.
- Background: PubMed 19376618Sozio SM, Armstrong PA, Coresh J, Jaar BG, Fink NE, Plantinga LC, Powe NR, Parekh RS. Cerebrovascular disease incidence, characteristics, and outcomes in patients initiating dialysis: the choices for healthy outcomes in caring for ESRD (CHOICE) study. Am J Kidney Dis. 2009 Sep;54(3):468-77. doi: 10.1053/j.ajkd.2009.01.261. Epub 2009 Apr 19.
- Background: PubMed 22429518Naganuma T, Takemoto Y, Shoji T, Shima H, Ishimura E, Okamura M, Nakatani T. Factors associated with cerebral white matter hyperintensities in haemodialysis patients. Nephrology (Carlton). 2012 Aug;17(6):561-8. doi: 10.1111/j.1440-1797.2012.01596.x.
- Background: PubMed 16864811Murray AM, Tupper DE, Knopman DS, Gilbertson DT, Pederson SL, Li S, Smith GE, Hochhalter AK, Collins AJ, Kane RL. Cognitive impairment in hemodialysis patients is common. Neurology. 2006 Jul 25;67(2):216-23. doi: 10.1212/01.wnl.0000225182.15532.40.
- Background: PubMed 23303848Sarnak MJ, Tighiouart H, Scott TM, Lou KV, Sorensen EP, Giang LM, Drew DA, Shaffi K, Strom JA, Singh AK, Weiner DE. Frequency of and risk factors for poor cognitive performance in hemodialysis patients. Neurology. 2013 Jan 29;80(5):471-80. doi: 10.1212/WNL.0b013e31827f0f7f. Epub 2013 Jan 9.
- Background: PubMed 15531623Skinner H, Mackaness C, Bedforth N, Mahajan R. Cerebral haemodynamics in patients with chronic renal failure: effects of haemodialysis. Br J Anaesth. 2005 Feb;94(2):203-5. doi: 10.1093/bja/aei016. Epub 2004 Nov 5.
- Background: PubMed 23620399Murray AM, Seliger S, Lakshminarayan K, Herzog CA, Solid CA. Incidence of stroke before and after dialysis initiation in older patients. J Am Soc Nephrol. 2013 Jun;24(7):1166-73. doi: 10.1681/ASN.2012080841. Epub 2013 Apr 25.
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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.
Mark D Findlay, MBChB principal investigator
University of Glasgow
Questions about this trial
What is this clinical trial studying?
An observational study of End-Stage Renal Disease and Stroke, run by NHS Greater Glasgow and Clyde.
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 1 inclusion and 6 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: status not confirmed, as of the sponsor's last update on 19 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Mark D Findlay, MBChB (01413304739, mark.findlay@glasgow.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression of white matter hyperintensities on MRI (time frame: 12 months). 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 NCT02393222, which also lists 6 linked publications.
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 19 Mar 2015; AzTrials last refreshed its copy on 1 Nov 2026.