End Stage Renal Disease and Cognitive ImpairmentBREINNCT04328415
Blood-Brain Barrier Evaluation In Nephrology (BREIN)
A study testing Cerebral scintigraphy in people with End Stage Renal Disease and Cognitive Impairment, run by Assistance Publique Hopitaux De Marseille at 1 site in France.
Trial summary
Patients with Chronic Kidney Disease (CKD) have impaired psycho-cognitive functions in parallel with deteriorating kidney function. The pathophysiology of cognitive impairment in CKD is poorly understood and there is currently no therapy to limit cognitive decline. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- End Stage Renal Disease and Cognitive Impairment
- What is being tested?
- Cerebral scintigraphy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteFrance
- Study dates
- 1 Jun 2020to 7 Jun 2022
- Phase
- Interventional
- 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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Patients :
- over 18 years old
- social security recipients
- in chronic hemodialysis at least 3 times 4 hours a week for at least 3 months
- having a negative pregnancy test less than 2 weeks old for women of childbearing age
- who have given informed consent to participate in the study
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- Healthy controls, matched in age (+/- 5 years) and sex to a patient :
- over 18 years old
- social security recipients
- having a negative pregnancy test less than 2 weeks old for women of childbearing age
- who have given informed consent to participate in the study
Who cannot join
- • Patients and healthy controls :
- Pregnant or breastfeeding women, a negative pregnancy test less than 2 weeks old will be required prior to inclusion for women of childbearing age.
- Majors under legal protection
- Lack of affiliation to a social security scheme
- Inability to give informed consent
- Persons deprived of liberty
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- Date of last menstrual period > 1 month in the absence of effective contraception in patients of childbearing age with a conserved menstrual cycle
- Known neurodegenerative disease
- Major Cardiovascular Disease : Unbalanced hypertension (defined as systolic blood pressure > 160 mmHg), history of stroke or coronary artery disease.
- Ongoing neoplastic or infectious disease
- Taking non-steroidal anti-inflammatory drugs within 48 hours before inclusion
- Ongoing drug treatment that may induce attention and/or cognitive deficits (anticholinergics, sedatives, neuroleptics)
- Known hypersensitivity to the radiotracer or a component of it
- Patients :
- Non-compliance with dialysis sessions
Trial locations and contacts
1 site in 1 country.
France1 site
Assistance Publique Des Hopitaux de Marseille
Marseille, 13354
Emilie GARRIDO-PRADALIE, +33 (0)4 91 38 27 47, drci@ap-hm.fr
Mickael BOBOT, +33 (0)4 91 38 30 42, mickael.bobot@ap-hm.fr
About this study
Official title: Evaluation of the Blood-brain Barrier Disruption During Chronic Kidney Disease by 99mTc-DTPA Cerebral Scintigraphy (BREIN)
Patients with Chronic Kidney Disease (CKD) have impaired psycho-cognitive functions in parallel with deteriorating kidney function. The pathophysiology of cognitive impairment in CKD is poorly understood and there is currently no therapy to limit cognitive decline. As kidney function deteriorates, uremic toxins accumulate in the patient's body. Their cerebral toxicity, whether direct or indirect through cerebral endothelial dysfunction, is a hypothesis that may explain the cognitive abnormalities, as well as the increased severity of strokes in patients with CKD. Among uremic toxins, indoxyl sulfate (IS) is an indolic toxin that is poorly purified by dialysis and whose high levels have already been shown to be associated with an increased cardiovascular risk in patients with CKD. Our hypothesis is that the psycho-cognitive disorders observed in patients with CKD are linked to cerebral endothelial dysfunction associated with high levels of IS.
In two models of CKD in rats, found impaired cognitive performance and increased blood-brain barrier (BBB) permeability, as assessed by brain scintigraphy with 99mTc-DTPA, compared to healthy control rats. Impaired cognitive performance was correlated with BBB permeability and circulating IS levels. Rats receiving an IS-enriched diet had higher BBB permeability and more impaired cognitive performance than MRC rats without an IS-enriched diet, suggesting a central role of IS.
Read more
The 99mTc-DTPA brain scintigraphy has already been used in clinical research to assess the BBB disruption after stroke, outside the context of CKD, and the tracer is available in human nuclear medicine.
Our hypothesis is that patients with CKD would have increased permeability of the BBB compared to healthy age- and sex-matched controls, and that this permeability would correlate with circulating levels of IS as in our preclinical animal models.
The main objective of this project is to evaluate the permeability of the BBB by brain scintigraphy with 99mTc-DTPA in patients with end-stage CKD and compare it to healthy age- and sex-matched controls.
A 18-month inclusion period will allow us to recruit 15 patients with end-stage CKD and 15 healthy volunteers matched in age and gender, as an important number of patients with end-stage CKD are followed in our department. If we confirm the results obtained in animal models, we will be able to propose the analysis of BBB disruption in isotope imaging as a criterion for evaluating therapeutic approaches modulating the toxicity of indolic uremic toxins in order to limit cognitive decline.
- Being tested
- Cerebral scintigraphy
- Medical subject headings
- Kidney Failure, Chronic, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cerebral scintigraphyRadiation
Radioactive tracer 99mTc-DTPA
| Study group | Role | What they receive |
|---|---|---|
| healthy volunteers | Experimental | Not described Receives: Radiation: Cerebral scintigraphy |
| patients with Chronic Kidney Disease | Experimental | Not described Receives: Radiation: Cerebral scintigraphy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ratio of intracerebral activity of 99mTc-DTPA (marker of BBB rupture) to total injected activity
Quantification of the intracerebral radioactivity of 99m-Tc DTPA by a senior nuclear physician, blinded from the other participants' data, in ratio to the total injected dose
Measured: 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Mar 2020
- Study start1 Jun 2020 (estimated)
- Primary completion7 Jan 2022 (estimated)
- Study completion7 Jun 2022 (estimated)
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 and Cognitive ImpairmentStudies of the same condition, open and under way.
- More trials run by Assistance Publique Hopitaux De MarseilleThe 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
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique Hopitaux De Marseille
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Emilie GARRIDO-PRADALIE, Study director, ASSISTANCE PUBLIQUE DES HOPITAUX DE MARSEILLE
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04328415
- Sponsor's protocol ID
- 2019-42
- Other IDs
- IDRCB
- Acronym
- BREIN
- Status last verified
- Mar 2020
- First submitted
- 28 Mar 2020
- Last updated
- 31 Mar 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Blood-brain Barrier Disruption During Chronic Kidney Disease by 99mTc-DTPA Cerebral Scintigraphy (BREIN)
- ClinicalTrials.gov ID
- NCT04328415
- Acronym / sponsor ID
- BREIN / 2019-42
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Assistance Publique Hopitaux De MarseilleUniversity, hospital or other
- Study start
- 1 Jun 2020 (estimated)
- Primary completion
- 7 Jan 2022 (estimated)
- Study completion
- 7 Jun 2022 (estimated)
- First posted
- 31 Mar 2020 (actual)
- 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.
Patients with Chronic Kidney Disease (CKD) have impaired psycho-cognitive functions in parallel with deteriorating kidney function. The pathophysiology of cognitive impairment in CKD is poorly understood and there is currently no therapy to limit cognitive decline. As kidney function deteriorates, uremic toxins accumulate in the patient's body. Their cerebral toxicity, whether direct or indirect through cerebral endothelial dysfunction, is a hypothesis that may explain the cognitive abnormalities, as well as the increased severity of strokes in patients with CKD. Among uremic toxins, indoxyl sulfate (IS) is an indolic toxin that is poorly purified by dialysis and whose high levels have already been shown to be associated with an increased cardiovascular risk in patients with CKD. Our hypothesis is that the psycho-cognitive disorders observed in patients with CKD are linked to cerebral endothelial dysfunction associated with high levels of IS.
In two models of CKD in rats, found impaired cognitive performance and increased blood-brain barrier (BBB) permeability, as assessed by brain scintigraphy with 99mTc-DTPA, compared to healthy control rats. Impaired cognitive performance was correlated with BBB permeability and circulating IS levels. Rats receiving an IS-enriched diet had higher BBB permeability and more impaired cognitive performance than MRC rats without an IS-enriched diet, suggesting a central role of IS.
The 99mTc-DTPA brain scintigraphy has already been used in clinical research to assess the BBB disruption after stroke, outside the context of CKD, and the tracer is available in human nuclear medicine.
Our hypothesis is that patients with CKD would have increased permeability of the BBB compared to healthy age- and sex-matched controls, and that this permeability would correlate with circulating levels of IS as in our preclinical animal models.
The main objective of this project is to evaluate the permeability of the BBB by brain scintigraphy with 99mTc-DTPA in patients with end-stage CKD and compare it to healthy age- and sex-matched controls.
A 18-month inclusion period will allow us to recruit 15 patients with end-stage CKD and 15 healthy volunteers matched in age and gender, as an important number of patients with end-stage CKD are followed in our department. If we confirm the results obtained in animal models, we will be able to propose the analysis of BBB disruption in isotope imaging as a criterion for evaluating therapeutic approaches modulating the toxicity of indolic uremic toxins in order to limit cognitive decline.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| healthy volunteers | Experimental | Radiation: Cerebral scintigraphy |
| patients with Chronic Kidney Disease | Experimental | Radiation: Cerebral scintigraphy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Patients :
- Healthy controls, matched in age (+/- 5 years) and sex to a patient :
Key exclusion criteria (15 listed)
- • Patients and healthy controls :
- Pregnant or breastfeeding women, a negative pregnancy test less than 2 weeks old will be required prior to inclusion for women of childbearing age.
- Majors under legal protection
- Lack of affiliation to a social security scheme
- Inability to give informed consent
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 |
|---|---|---|
| Cerebral scintigraphyRadioactive tracer 99mTc-DTPA | Radiation | healthy volunteers, patients with Chronic Kidney Disease |
Primary outcome
Ratio of intracerebral activity of 99mTc-DTPA (marker of BBB rupture) to total injected activity
Time frame: 1 day
Quantification of the intracerebral radioactivity of 99m-Tc DTPA by a senior nuclear physician, blinded from the other participants' data, in ratio to the total injected dose
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Mar 2020.
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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.
Emilie GARRIDO-PRADALIE study director
ASSISTANCE PUBLIQUE DES HOPITAUX DE MARSEILLE
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cerebral scintigraphy in people with End Stage Renal Disease and Cognitive Impairment, run by Assistance Publique Hopitaux De Marseille at 1 site in France.
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 11 inclusion and 15 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 31 Mar 2020. 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 France. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Mickael BOBOT (+33 (0)4 91 38 30 42, mickael.bobot@ap-hm.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Ratio of intracerebral activity of 99mTc-DTPA (marker of BBB rupture) to total injected activity (time frame: 1 day). 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 31 Mar 2020.