Aneurysmal Subarachnoid HemorrhageNCT03706768
Degradation of the Glycocalyx in Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage
A study testing Glycocalyx in people with Aneurysmal Subarachnoid Hemorrhage, run by University of Virginia at 1 site in United States.
Trial summary
This study will provide novel information to the literature base for the pathophysiology of aneurysmal subarachnoid hemorrhage. The association of breakdown products in the serum of aSAH patients were reported in a very small case series of 3 patients, as mentioned above. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Aneurysmal Subarachnoid Hemorrhage
- What is being tested?
- Glycocalyx
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 1 siteUnited States
- Study dates
- 1 May 2018to 1 May 2020
- 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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- • Age 18 years of age and older
- Cerebral aneurysm on CT-angio
Who cannot join
- • comfort care only orders,
- the absence of an aneurysm on CT-angiography,
- onset of aneurysm rupture > 24 hours,
- and inability to obtain informed consent from patient or family pregnant women
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
University of Virginia Health System
Charlottesville, Virginia, 22908
Marcia E Birk
About this study
This study will provide novel information to the literature base for the pathophysiology of aneurysmal subarachnoid hemorrhage. The association of breakdown products in the serum of aSAH patients were reported in a very small case series of 3 patients, as mentioned above. However, while their results are intriguing and encouraging, our study will provide more definitive information about the GC in aSAH. If there is a positive correlation, the results of this study will guide future investigations into new therapies for this devastating disease such as MMP inhibition with doxycycline.
Read the detailed description
- The study will aim to recruit all eligible patients at UTMCK and the University of Virginia hospital over a 12 month period. Our main outcome measure is degradation of the glycocalyx in patients with aSAH. All eligible patients with confirmed aSAH admitted to the neuro-intensive care unit will be enrolled after consent is obtained from the family and/or the patient. Serum samples will be drawn from each patient on admission (day 1) and every other day until day 13 for a total of 7 samples per patient. The following serum tests will be performed:
- Measurement of serum syndecan-1 by ELISA
- Measurement of serum heparan-sulfate by ELISA
- Measurement of serum matrix metalloproteinases -9
- Measurement of serum matrix-metalloproteinase-1
- Measurement of urinary microalbumin-to-creatinine ratio
- Measurement of daily TCDs (all patients currently receive daily TCDs as part of the aSAH protocol at UTMCK and UVA Hospital)
- Outcomes:
- Chart review: i) Incidence of DCI as defined by a consensus committee on this subject and published in the journal Stroke [29]. ii) In-hospital mortality will be recorded b) Follow-up performed by phone call or searching the Social Security Death Index [30]: i) 30-day mortality ii) 90-day mortality c) Outcomes follow-up: i) The Glasgow Outcome Scale 12 weeks post aSAH [31]
- Conditions
- Aneurysmal Subarachnoid Hemorrhage
- Being tested
- Glycocalyx
- Medical subject headings
- Subarachnoid Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GlycocalyxOther
Measure Degradation of the Glycocalyx
| Study group | Role | What they receive |
|---|---|---|
| Glycocalyx | Other | degree of glycocalyx breakdown in patients with aSAH Receives: Other: Glycocalyx |
What is being measured
The primary outcome is the main question the study is designed to answer.
Syndecan-1 and heparin sulfate
Compare the degree of glycocalyx breakdown in patients with aSAH who develop delayed cerebral ischemia (DCI) to those that do not develop DCI. This will be completed by measuring the breakdown of Syndecan-1 and heparin sulfate in the blood.
Measured: day 0 through day 13
Secondary outcomes (2)
serum Matrix metalloproteinase-1 and Matrix metalloproteinase-9
serum MMP-9 and MMP-1 will be levels will be measured as serum MMP concentrations have been positively correlated with the incidence of delayed cerebral ishemia
Measured: day 0 through day 13
urinary microalbumin-to-creatinine ratio (MACR)
urinary microalbumin-to-creatinine ratio (MACR) will be measured as it is marker of systemic damage to the glycocalyx
Measured: day 0 through day13
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Oct 2018
- Study start1 May 2018
- Primary completion1 May 2020 (estimated)
- Study completion1 May 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (28)Papers the sponsor has linked to this study.
- Other trials for Aneurysmal Subarachnoid HemorrhageStudies of the same condition, open and under way.
- More trials run by University of VirginiaThe 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
- Not applicable
- Intervention model
- Single group
- Model description
- Aneurysmal Subarachnoid Hemorrhage
- Masking
- None (open label)
- Enrolment
- 42 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Virginia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Danny Theodore, MD, University of Virginia
- Investigators
- Daniel Theodore, MD, Principal investigator, University of Virginia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03706768
- Sponsor's protocol ID
- 170016
- Status last verified
- Apr 2019
- First submitted
- 11 Oct 2018
- Last updated
- 25 Apr 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Bogason ET, Anderson B, Brandmeir NJ, Church EW, Cooke J, Davies GM, Hussain N, Patel AS, Payne R, Rohatgi P, Sieg E, Zalatimo O, Ziu E. The epidemiology of admissions of nontraumatic subarachnoid hemorrhage in the United States. Neurosurgery. 2014 Feb;74(2):227-9. doi: 10.1227/NEU.0000000000000240. No abstract available.
PubMed 24435139Macdonald RL, Higashida RT, Keller E, Mayer SA, Molyneux A, Raabe A, Vajkoczy P, Wanke I, Bach D, Frey A, Marr A, Roux S, Kassell N. Clazosentan, an endothelin receptor antagonist, in patients with aneurysmal subarachnoid haemorrhage undergoing surgical clipping: a randomised, double-blind, placebo-controlled phase 3 trial (CONSCIOUS-2). Lancet Neurol. 2011 Jul;10(7):618-25. doi: 10.1016/S1474-4422(11)70108-9. Epub 2011 Jun 2.
PubMed 21640651Rowland MJ, Hadjipavlou G, Kelly M, Westbrook J, Pattinson KT. Delayed cerebral ischaemia after subarachnoid haemorrhage: looking beyond vasospasm. Br J Anaesth. 2012 Sep;109(3):315-29. doi: 10.1093/bja/aes264.
PubMed 22879655Collins SR, Blank RS, Deatherage LS, Dull RO. Special article: the endothelial glycocalyx: emerging concepts in pulmonary edema and acute lung injury. Anesth Analg. 2013 Sep;117(3):664-674. doi: 10.1213/ANE.0b013e3182975b85. Epub 2013 Jul 8.
PubMed 23835455Alphonsus CS, Rodseth RN. The endothelial glycocalyx: a review of the vascular barrier. Anaesthesia. 2014 Jul;69(7):777-84. doi: 10.1111/anae.12661. Epub 2014 Apr 28.
PubMed 24773303Yang Y, Schmidt EP. The endothelial glycocalyx: an important regulator of the pulmonary vascular barrier. Tissue Barriers. 2013 Jan 1;1(1):e23494. doi: 10.4161/tisb.23494.
PubMed 24073386Singh A, Ramnath RD, Foster RR, Wylie EC, Friden V, Dasgupta I, Haraldsson B, Welsh GI, Mathieson PW, Satchell SC. Reactive oxygen species modulate the barrier function of the human glomerular endothelial glycocalyx. PLoS One. 2013;8(2):e55852. doi: 10.1371/journal.pone.0055852. Epub 2013 Feb 14.
PubMed 23457483Ince C, Mayeux PR, Nguyen T, Gomez H, Kellum JA, Ospina-Tascon GA, Hernandez G, Murray P, De Backer D; ADQI XIV Workgroup. THE ENDOTHELIUM IN SEPSIS. Shock. 2016 Mar;45(3):259-70. doi: 10.1097/SHK.0000000000000473.
PubMed 26871664Bell JD, Rhind SG, Di Battista AP, Macdonald RL, Baker AJ. Biomarkers of Glycocalyx Injury are Associated with Delayed Cerebral Ischemia Following Aneurysmal Subarachnoid Hemorrhage: A Case Series Supporting a New Hypothesis. Neurocrit Care. 2017 Jun;26(3):339-347. doi: 10.1007/s12028-016-0357-4.
PubMed 28000132Becker BF, Jacob M, Leipert S, Salmon AH, Chappell D. Degradation of the endothelial glycocalyx in clinical settings: searching for the sheddases. Br J Clin Pharmacol. 2015 Sep;80(3):389-402. doi: 10.1111/bcp.12629. Epub 2015 May 22.
PubMed 25778676Lipowsky HH. The endothelial glycocalyx as a barrier to leukocyte adhesion and its mediation by extracellular proteases. Ann Biomed Eng. 2012 Apr;40(4):840-8. doi: 10.1007/s10439-011-0427-x. Epub 2011 Oct 8.
PubMed 21984514Triglia T, Mezzapesa A, Martin JC, Verdier M, Lagier D, Dufour H, Bruder N, Alessi MC, Velly LJ. Early matrix metalloproteinase-9 concentration in the first 48 h after aneurysmal subarachnoid haemorrhage predicts delayed cerebral ischaemia: An observational study. Eur J Anaesthesiol. 2016 Sep;33(9):662-9. doi: 10.1097/EJA.0000000000000494.
PubMed 27355865Tromp J, van der Pol A, Klip IT, de Boer RA, Jaarsma T, van Gilst WH, Voors AA, van Veldhuisen DJ, van der Meer P. Fibrosis marker syndecan-1 and outcome in patients with heart failure with reduced and preserved ejection fraction. Circ Heart Fail. 2014 May;7(3):457-62. doi: 10.1161/CIRCHEARTFAILURE.113.000846. Epub 2014 Mar 19.
PubMed 24647119Neves FM, Meneses GC, Sousa NE, Menezes RR, Parahyba MC, Martins AM, Liborio AB. Syndecan-1 in Acute Decompensated Heart Failure--Association With Renal Function and Mortality. Circ J. 2015;79(7):1511-9. doi: 10.1253/circj.CJ-14-1195. Epub 2015 Apr 17.
PubMed 25891890Ostrowski SR, Gaini S, Pedersen C, Johansson PI. Sympathoadrenal activation and endothelial damage in patients with varying degrees of acute infectious disease: an observational study. J Crit Care. 2015 Feb;30(1):90-6. doi: 10.1016/j.jcrc.2014.10.006. Epub 2014 Oct 8.
PubMed 25457118
Study at a glance
From the registry record, last updated by the sponsor on 25 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Degradation of the Glycocalyx in Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage
- ClinicalTrials.gov ID
- NCT03706768
- Acronym / sponsor ID
- 170016
- Conditions
- Aneurysmal Subarachnoid Hemorrhage
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 42 participants (estimated)
- Lead sponsor
- University of VirginiaUniversity, hospital or other
- Study start
- 1 May 2018 (actual)
- Primary completion
- 1 May 2020 (estimated)
- Study completion
- 1 May 2020 (estimated)
- First posted
- 16 Oct 2018 (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 study will provide novel information to the literature base for the pathophysiology of aneurysmal subarachnoid hemorrhage. The association of breakdown products in the serum of aSAH patients were reported in a very small case series of 3 patients, as mentioned above. However, while their results are intriguing and encouraging, our study will provide more definitive information about the GC in aSAH. If there is a positive correlation, the results of this study will guide future investigations into new therapies for this devastating disease such as MMP inhibition with doxycycline.
Detailed description
- The study will aim to recruit all eligible patients at UTMCK and the University of Virginia hospital over a 12 month period. Our main outcome measure is degradation of the glycocalyx in patients with aSAH. All eligible patients with confirmed aSAH admitted to the neuro-intensive care unit will be enrolled after consent is obtained from the family and/or the patient. Serum samples will be drawn from each patient on admission (day 1) and every other day until day 13 for a total of 7 samples per patient. The following serum tests will be performed:
- Measurement of serum syndecan-1 by ELISA
- Measurement of serum heparan-sulfate by ELISA
- Measurement of serum matrix metalloproteinases -9
- Measurement of serum matrix-metalloproteinase-1
- Measurement of urinary microalbumin-to-creatinine ratio
- Measurement of daily TCDs (all patients currently receive daily TCDs as part of the aSAH protocol at UTMCK and UVA Hospital)
- Outcomes:
- Chart review: i) Incidence of DCI as defined by a consensus committee on this subject and published in the journal Stroke [29]. ii) In-hospital mortality will be recorded b) Follow-up performed by phone call or searching the Social Security Death Index [30]: i) 30-day mortality ii) 90-day mortality c) Outcomes follow-up: i) The Glasgow Outcome Scale 12 weeks post aSAH [31]
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Aneurysmal Subarachnoid Hemorrhage
| Arm | Type | Receives |
|---|---|---|
| Glycocalyx | Other | Other: Glycocalyxdegree of glycocalyx breakdown in patients with aSAH |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- • Age 18 years of age and older
Key exclusion criteria (4 listed)
- • comfort care only orders,
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 |
|---|---|---|
| GlycocalyxMeasure Degradation of the Glycocalyx | Other | Glycocalyx |
Primary outcome
Syndecan-1 and heparin sulfate
Time frame: day 0 through day 13
Compare the degree of glycocalyx breakdown in patients with aSAH who develop delayed cerebral ischemia (DCI) to those that do not develop DCI. This will be completed by measuring the breakdown of Syndecan-1 and heparin sulfate in the blood.
2 secondary outcomes
serum Matrix metalloproteinase-1 and Matrix metalloproteinase-9
Time frame: day 0 through day 13
urinary microalbumin-to-creatinine ratio (MACR)
Time frame: day 0 through day13
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Apr 2019.
- Background: PubMed 24435139Bogason ET, Anderson B, Brandmeir NJ, Church EW, Cooke J, Davies GM, Hussain N, Patel AS, Payne R, Rohatgi P, Sieg E, Zalatimo O, Ziu E. The epidemiology of admissions of nontraumatic subarachnoid hemorrhage in the United States. Neurosurgery. 2014 Feb;74(2):227-9. doi: 10.1227/NEU.0000000000000240. No abstract available.
- Background: PubMed 21640651Macdonald RL, Higashida RT, Keller E, Mayer SA, Molyneux A, Raabe A, Vajkoczy P, Wanke I, Bach D, Frey A, Marr A, Roux S, Kassell N. Clazosentan, an endothelin receptor antagonist, in patients with aneurysmal subarachnoid haemorrhage undergoing surgical clipping: a randomised, double-blind, placebo-controlled phase 3 trial (CONSCIOUS-2). Lancet Neurol. 2011 Jul;10(7):618-25. doi: 10.1016/S1474-4422(11)70108-9. Epub 2011 Jun 2.
- Background: PubMed 22879655Rowland MJ, Hadjipavlou G, Kelly M, Westbrook J, Pattinson KT. Delayed cerebral ischaemia after subarachnoid haemorrhage: looking beyond vasospasm. Br J Anaesth. 2012 Sep;109(3):315-29. doi: 10.1093/bja/aes264.
- Background: PubMed 23835455Collins SR, Blank RS, Deatherage LS, Dull RO. Special article: the endothelial glycocalyx: emerging concepts in pulmonary edema and acute lung injury. Anesth Analg. 2013 Sep;117(3):664-674. doi: 10.1213/ANE.0b013e3182975b85. Epub 2013 Jul 8.
- Background: PubMed 24773303Alphonsus CS, Rodseth RN. The endothelial glycocalyx: a review of the vascular barrier. Anaesthesia. 2014 Jul;69(7):777-84. doi: 10.1111/anae.12661. Epub 2014 Apr 28.
- Background: PubMed 24073386Yang Y, Schmidt EP. The endothelial glycocalyx: an important regulator of the pulmonary vascular barrier. Tissue Barriers. 2013 Jan 1;1(1):e23494. doi: 10.4161/tisb.23494.
- Background: PubMed 23457483Singh A, Ramnath RD, Foster RR, Wylie EC, Friden V, Dasgupta I, Haraldsson B, Welsh GI, Mathieson PW, Satchell SC. Reactive oxygen species modulate the barrier function of the human glomerular endothelial glycocalyx. PLoS One. 2013;8(2):e55852. doi: 10.1371/journal.pone.0055852. Epub 2013 Feb 14.
- Background: PubMed 26871664Ince C, Mayeux PR, Nguyen T, Gomez H, Kellum JA, Ospina-Tascon GA, Hernandez G, Murray P, De Backer D; ADQI XIV Workgroup. THE ENDOTHELIUM IN SEPSIS. Shock. 2016 Mar;45(3):259-70. doi: 10.1097/SHK.0000000000000473.
- Background: PubMed 28000132Bell JD, Rhind SG, Di Battista AP, Macdonald RL, Baker AJ. Biomarkers of Glycocalyx Injury are Associated with Delayed Cerebral Ischemia Following Aneurysmal Subarachnoid Hemorrhage: A Case Series Supporting a New Hypothesis. Neurocrit Care. 2017 Jun;26(3):339-347. doi: 10.1007/s12028-016-0357-4.
- Background: PubMed 25778676Becker BF, Jacob M, Leipert S, Salmon AH, Chappell D. Degradation of the endothelial glycocalyx in clinical settings: searching for the sheddases. Br J Clin Pharmacol. 2015 Sep;80(3):389-402. doi: 10.1111/bcp.12629. Epub 2015 May 22.
- Background: PubMed 21984514Lipowsky HH. The endothelial glycocalyx as a barrier to leukocyte adhesion and its mediation by extracellular proteases. Ann Biomed Eng. 2012 Apr;40(4):840-8. doi: 10.1007/s10439-011-0427-x. Epub 2011 Oct 8.
- Background: PubMed 27355865Triglia T, Mezzapesa A, Martin JC, Verdier M, Lagier D, Dufour H, Bruder N, Alessi MC, Velly LJ. Early matrix metalloproteinase-9 concentration in the first 48 h after aneurysmal subarachnoid haemorrhage predicts delayed cerebral ischaemia: An observational study. Eur J Anaesthesiol. 2016 Sep;33(9):662-9. doi: 10.1097/EJA.0000000000000494.
- Individual participant dataSharing planned: Undecided
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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.
Daniel Theodore, MD principal investigator
University of Virginia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Glycocalyx in people with Aneurysmal Subarachnoid Hemorrhage, run by University of Virginia at 1 site in United States.
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 4 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 25 Apr 2019. 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 United States. 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 Marcia E Birk (434-924-2283, meb2w@virginia.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Syndecan-1 and heparin sulfate (time frame: day 0 through day 13). 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 NCT03706768, which also lists 28 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 25 Apr 2019.