ESRDNCT03241667
Blood Flow Effects on Silicon Substrates
An observational study of ESRD, run by University of California, San Francisco.
Trial summary
This is a non-randomized, open label, uncontrolled first in human safety study, testing the the material used in the artificial kidney device in subjects already on hemodialysis. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- ESRD
- What is being tested?
- HemoCartridge
- Type of treatment
- Medical device
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 15 Jul 2019to 30 Jun 2020
- 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 75 years
- All sexes
- Adult, Older adult
Study population: ESRD
Who may be able to join
- 18-75 y/o
- ESRD on hemodialysis for at least 3 months
- HD access capable of sustaining at least 300 ml/min blood flow
- Hg > 10.0 g
- Able to take aspirin 81 mg/day for a week prior to the study (for those subjects not already on aspirin)
- Able to read, speak and understand English
- Capable of providing signed informed consent
- HD pt at one of the UCSF outpatient HD units
Who cannot join
- Subjects with active liver, cardiovascular, neurologic or psychiatric diseases
- Subjects with other active medical problems (e.g., cancer undergoing treatment)
- h/o intradialytic or orthostatic hypotension
- h/o thrombosis or on treatment for thrombosis or use of anticoagulants, excluding antiplatelet agents
- h/o active infection or on antibiotics
- h/o active autoimmune diseases or other inflammatory states
Show all 10Show fewer
- Ongoing alcohol or illegal drug use
- Pregnant
- H/o hemolysis or allergic reactions to any dialyzers
- Anyone who in the opinion of the study doctors is not qualified to be in the study.
About this study
This is a non-randomized, open label, uncontrolled first in human safety study, testing the the material used in the artificial kidney device in subjects already on hemodialysis.
Six subjects already on hemodialysis, who meet the study inclusion and exclusion criteria, and who dialyze at one of the UCSF associated hemodialysis units will be recruited. Each subject will be tested during one non hemodialysis day, at the UCSF Moffitt-Long Hospital Acute Hemodialysis Unit (AHU).
The artificial kidney engineers have created a blood flow system that can be substituted for the dialysis filter in a standard hemodialysis machine. This is NOT a dialysis filter. It allows the subjects blood to come in contact with the material while the blood is being circulated as is regularly done during a hemodialysis session.
Read the detailed description
For patient safety, the investigators will measure the following labs:
Blood tests (routine safety and frequency). CBC/platelets: q 1 hr, at HD next day ABGs, including lactate: Q 1 hr x 6 Na, K, Cl, Bicarb, BUN, Creatinine, Ca, ionized Ca, Mg, Phos: Start, end, at HD next day Liver function test: Start, end, at HD next day LDH: Start, end, at HD next day Direct Coombs' Test: Start, end, at HD next day ESR and hsCRP: Start, end, at HD next day CPK: Start, end PT/PTT: Start, end
The investigators will also be doing research blood testing:
IL-6: Start, end, at HD next day Complement: Start, end, at HD next day Haptoglobin: Start, end, at HD next day Free Hg: Start, end, at HD next day Fibrinogen, D-dimer: Start, end, at HD next day
In addition, the investigators will do material testing after each participant's test is complete.
Material studies after in vivo testing :
Cell and Protein Adhesion Studies:
- Scanning Electron Microscopy. The SNM will be placed in a solution containing 2% glutaraldehyde (Electron Microscopy Sciences, Fort Washington, PA), 3% sucrose (Sigma Aldrich) and 0.1 M of phosphate buffered saline (PBS) at 4°C and pH 7.4. After 1 hour, the substrates are rinsed twice with PBS for 30 minutes at 4°C and washed with distilled water for 5 minutes. Dehydration is achieved by placing the substrates in 50% ethanol for 15 minutes while increasing the concentration of ethanol to 60%, 70%, 80%, 90%, and finally 100%. Dehydrated samples are then mounted on aluminum stubs, sputter-coated with gold-palladium, and examined using Scanning Electron Microscopy (SEM; Ultra55 FEGSEM, ZEISS, Peabody, MA).
- Immunohistochemistry. Platelet adhesion and activation are assessed using immunofluorescence staining for the platelet marker, CD41 (Abcam, Cambridge, MA), and blood-clot marker, tissue plasminogen activator (t-PA, Abcam, Cambridge, MA). Platelets are fixed in 4% paraformaldehyde (Fisher Scientific, Waltham, MA) for 15 minutes followed by incubation in 1% bovine serum albumin for 30 minutes to block nonspecific binding. Platelets are double-labeled as follows: substrates were first incubated with primary antibodies (t-PA), diluted 1:50 in PBS for 60 minutes followed by Alexa Fluor 546 donkey anti-mouse antibody (Invitrogen, Carlsbad, CA) diluted 1:100 in PBS for 60 minutes. Finally, the samples are incubated with anti-human CD41 fluorescein isothiocyanate labeled mouse monoclonal antibody diluted 1:300 in PBS for 60 minutes. Images will be acquired per replicate using a Nikon Eclipse Ti-E motorized inverted microscope (Nikon Instruments Inc., Melville, NY) to obtain a total of 12 images per substrate. The fluorescent intensity of the images is quantified using ImageJ.
- Conditions
- ESRD
- Being tested
- HemoCartridge
- 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.
HemoCartridgeDevice
Our goal is to apply MEMS (microelectromechanical systems) and nanotechnology to miniaturize the bioartificial kidney (BAK) into an implantable, self-monitoring, and self-regulating renal surrogate. The implantable BAK (iBAK) is a biocompatible cartridge containing stacks of hemofilter membranes (HemoCartridge) and renal tubule cell bioreactors (BioCartridge) combined to mimic nephron function. Here, we plan to test ONLY the material being used to construct the HemoCartridge, to be sure in humans when substituted for a standard hemodialysis filter, subjects don't develop any clinical problems or side effects during several hours of blood exposure to the material. The AK material will be engineered by the study team to allow the system to be substituted in place of a standard HD filter.
What is being measured
The primary outcome is the main question the study is designed to answer.
material stability
This is a first in human safety study, testing the safety of the material used in the artificial kidney device in subjects already on hemodialysis.
Specific aims include:
Aim 1: To prove that blood does not degrade the material (see study description for details of processes used) 1.a. by evaluating the effect on surface roughness via scanning electron microscopy of the hemocartridge plates
- b. by studying the effect on film thickness via scanning electron microscopy and immunohistochemistry for platelet adhesion.
Measured: 6 months
effects of the hemocartridge materials on inflammatory and coagulation factors in blood
Aim 2: To prove that this material is does not induce inflammatory or coagulation effects nor induce hemolysis. The investigators will do this by drawing blood before, during and after the procedure for inflammatory markers and coagulation factors. The investigators will also evaluate whether any evidence of mechanical dysfunction, such as hemolysis occurs during the treatment. See the detailed study description for the listing and timing of the tests.
1.c. evaluation of mechanical dysfunction
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2017
- Study start15 Jul 2019 (estimated)
- Primary completion15 Feb 2020 (estimated)
- Study completion30 Jun 2020 (estimated)
Why it stopped: IRB application withdrawn
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ESRDStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe 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
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Shuvo Roy, PhD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03241667
- Sponsor's protocol ID
- AK2017
- Status last verified
- Feb 2020
- First submitted
- 26 Jul 2017
- Last updated
- 28 Feb 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Blood Flow Effects on Silicon Substrates
- ClinicalTrials.gov ID
- NCT03241667
- Acronym / sponsor ID
- AK2017
- Conditions
- ESRD
- Study type
- Observational
- Recruitment status
- WithdrawnReason stopped: IRB application withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Study start
- 15 Jul 2019 (estimated)
- Primary completion
- 15 Feb 2020 (estimated)
- Study completion
- 30 Jun 2020 (estimated)
- First posted
- 7 Aug 2017 (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.
This is a non-randomized, open label, uncontrolled first in human safety study, testing the the material used in the artificial kidney device in subjects already on hemodialysis.
Six subjects already on hemodialysis, who meet the study inclusion and exclusion criteria, and who dialyze at one of the UCSF associated hemodialysis units will be recruited. Each subject will be tested during one non hemodialysis day, at the UCSF Moffitt-Long Hospital Acute Hemodialysis Unit (AHU).
The artificial kidney engineers have created a blood flow system that can be substituted for the dialysis filter in a standard hemodialysis machine. This is NOT a dialysis filter. It allows the subjects blood to come in contact with the material while the blood is being circulated as is regularly done during a hemodialysis session.
Detailed description
For patient safety, the investigators will measure the following labs:
Blood tests (routine safety and frequency). CBC/platelets: q 1 hr, at HD next day ABGs, including lactate: Q 1 hr x 6 Na, K, Cl, Bicarb, BUN, Creatinine, Ca, ionized Ca, Mg, Phos: Start, end, at HD next day Liver function test: Start, end, at HD next day LDH: Start, end, at HD next day Direct Coombs' Test: Start, end, at HD next day ESR and hsCRP: Start, end, at HD next day CPK: Start, end PT/PTT: Start, end
The investigators will also be doing research blood testing:
IL-6: Start, end, at HD next day Complement: Start, end, at HD next day Haptoglobin: Start, end, at HD next day Free Hg: Start, end, at HD next day Fibrinogen, D-dimer: Start, end, at HD next day
In addition, the investigators will do material testing after each participant's test is complete.
Material studies after in vivo testing :
Cell and Protein Adhesion Studies:
- Scanning Electron Microscopy. The SNM will be placed in a solution containing 2% glutaraldehyde (Electron Microscopy Sciences, Fort Washington, PA), 3% sucrose (Sigma Aldrich) and 0.1 M of phosphate buffered saline (PBS) at 4°C and pH 7.4. After 1 hour, the substrates are rinsed twice with PBS for 30 minutes at 4°C and washed with distilled water for 5 minutes. Dehydration is achieved by placing the substrates in 50% ethanol for 15 minutes while increasing the concentration of ethanol to 60%, 70%, 80%, 90%, and finally 100%. Dehydrated samples are then mounted on aluminum stubs, sputter-coated with gold-palladium, and examined using Scanning Electron Microscopy (SEM; Ultra55 FEGSEM, ZEISS, Peabody, MA).
- Immunohistochemistry. Platelet adhesion and activation are assessed using immunofluorescence staining for the platelet marker, CD41 (Abcam, Cambridge, MA), and blood-clot marker, tissue plasminogen activator (t-PA, Abcam, Cambridge, MA). Platelets are fixed in 4% paraformaldehyde (Fisher Scientific, Waltham, MA) for 15 minutes followed by incubation in 1% bovine serum albumin for 30 minutes to block nonspecific binding. Platelets are double-labeled as follows: substrates were first incubated with primary antibodies (t-PA), diluted 1:50 in PBS for 60 minutes followed by Alexa Fluor 546 donkey anti-mouse antibody (Invitrogen, Carlsbad, CA) diluted 1:100 in PBS for 60 minutes. Finally, the samples are incubated with anti-human CD41 fluorescein isothiocyanate labeled mouse monoclonal antibody diluted 1:300 in PBS for 60 minutes. Images will be acquired per replicate using a Nikon Eclipse Ti-E motorized inverted microscope (Nikon Instruments Inc., Melville, NY) to obtain a total of 12 images per substrate. The fluorescent intensity of the images is quantified using ImageJ.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- ESRD
Key inclusion criteria (8 listed)
- 18-75 y/o
- ESRD on hemodialysis for at least 3 months
- HD access capable of sustaining at least 300 ml/min blood flow
- Hg > 10.0 g
- Able to take aspirin 81 mg/day for a week prior to the study (for those subjects not already on aspirin)
Key exclusion criteria (10 listed)
- Subjects with active liver, cardiovascular, neurologic or psychiatric diseases
- Subjects with other active medical problems (e.g., cancer undergoing treatment)
- h/o intradialytic or orthostatic hypotension
- h/o thrombosis or on treatment for thrombosis or use of anticoagulants, excluding antiplatelet agents
- h/o active infection or on antibiotics
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 |
|---|---|---|
| HemoCartridgeOur goal is to apply MEMS (microelectromechanical systems) and nanotechnology to miniaturize the bioartificial kidney (BAK) into an implantable, self-monitoring, and self-regulating renal surrogate. The implantable BAK (iBAK) is a biocompatible cartridge containing stacks of hemofilter membranes (HemoCartridge) and renal tubule cell bioreactors (BioCartridge) combined to mimic nephron function. Here, we plan to test ONLY the material being used to construct the HemoCartridge, to be sure in humans when substituted for a standard hemodialysis filter, subjects don't develop any clinical problems or side effects during several hours of blood exposure to the material. The AK material will be engineered by the study team to allow the system to be substituted in place of a standard HD filter. | Device | – |
Primary outcome
material stability
Time frame: 6 months
This is a first in human safety study, testing the safety of the material used in the artificial kidney device in subjects already on hemodialysis. Specific aims include: Aim 1: To prove that blood does not degrade the material (see study description for details of processes used) 1.a. by evaluating the effect on surface roughness via scanning electron microscopy of the hemocartridge plates 1. b. by studying the effect on film thickness via scanning electron microscopy and immunohistochemistry for platelet adhesion.
effects of the hemocartridge materials on inflammatory and coagulation factors in blood
Time frame: 6 months
Aim 2: To prove that this material is does not induce inflammatory or coagulation effects nor induce hemolysis. The investigators will do this by drawing blood before, during and after the procedure for inflammatory markers and coagulation factors. The investigators will also evaluate whether any evidence of mechanical dysfunction, such as hemolysis occurs during the treatment. See the detailed study description for the listing and timing of the tests. 1.c. evaluation of mechanical dysfunction
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2020.
- Individual participant dataSharing planned: No
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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.
Shuvo Roy, PhD principal investigator
University of California, San Francisco
Questions about this trial
What is this clinical trial studying?
An observational study of ESRD, run by University of California, San Francisco.
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 8 inclusion and 10 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: withdrawn, as of the sponsor's last update on 28 Feb 2020. 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?
The study was withdrawn before enrolling participants, so there are no results.
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?
material stability (time frame: 6 months). 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 28 Feb 2020.