Safety and Efficacy of NBO in Acute Intracerebral Hemorrhage

Cerebral Hemorrhage Clinical Trial

Official title:

Safety and Efficacy of NBO in Acute Intracerebral Hemorrhage

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04144868
• Other study ID #: NBO-ICH
• Status: Not yet recruiting
• Phase: N/A
• Start date: October 30, 2019
• Est. completion date: December 30, 2020

Study information

• Verified date: October 2019
• Source: Capital Medical University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Intracerebral hemorrhage (ICH) is one of the most devastating nontraumatic cerebral vascular diseases. Its exacerbation is often related to a mass effect because of hematoma formation and edema in the perihematoma, which plays a key role in disease deterioration. Perihematoma edema is an important contributor to brain injuries secondary to ICH and one of the risk factors that leads to disease deterioration and high mortality. Brain edema following ICH was believed to be induced by the breakdown of the blood-brain barrier and ischemia and hypoxia of the perihematoma.

Normobaric oxygen (NBO) therapy is a treatment that delivers high-flow oxygen at normobaric pressure through a facemask to supplement the oxygen supply,which maintain the oxygen concentration of typically 40-100% ,can increase the arterial oxygen content, and alleviate tissue hypoxia. NBO therapy has been shown to provide neuroprotection against ischemic stroke in an experimental study and a clinical trial. To the best of our knowledge, the potential of NBO therapy for neuroprotection against human hemorrhagic stroke has not been investigated.

There are two studies about NBO interventions in the rat model of intracerebral hemorrhage.The one showed NBO did not worsen hemorrhage severity or brain edema. There were no significant differences in hemorrhagic blood volumes or brain water content. NBO did not affect any of the neurological outcome tests in the primary or secondary studies. Another one showed NBO groups improved NSSs,decreased contents of brain water, HIF-1α and VEGF, and fewer apoptotic cells in the perihematoma at 72 h after ICH compared with the ICH control group. These results suggest that NBO therapy with oxygen delivered at 90% conferred best neuroprotection to ICH rats, potentially through amelioration of brain edema by suppressing HIF-1α and VEGF expression in the perihematoma.

But there is no clinical study on the safety and efficacy of NBO in patients with intracerebral hemorrhage.NBO has the advantages of simple operation, non-invasiveness and early application, which makes it have great application prospects in the treatment of ICH.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: December 30, 2020
• Est. primary completion date: August 8, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Patient Age = 18 and = 80 years;

2. The diagnosis of ICH is confirmed by brain CT scan;

3. NIHSS score = 6 and GCS > 8 upon presentation;

4. Functional independence prior to ICH, defined as pre-ICH mRS = 1

5. Signed and dated informed consent is obtained.

Exclusion Criteria:

1. Known history of severe chronic obstructive pulmonary disease (Forced Expiratory Vital Capacity less than 1.0L or oxygen dependent).

2. New York Heart Association Class III heart failure.

3. Patient will undergo surgical evacuation of ICH .

4. Inability to undergo neuroimaging with MRI .

5. GCS <8

6. Baseline mRS = 2

7. Intraparenchymal hematoma secondary to rupture of cerebral aneurysm or bleeding of arteriovenous (A-V) malformation or cerebral tumors

8. Any condition which, in the judgment of the investigator, might increase the risk to the patient.

Related Conditions & MeSH terms

• Cerebral Hemorrhage
• Hemorrhage
• Normobaric Oxygen

Intervention

Other:
• Normobaric Oxygen

Locations

Country	Name	City	State
China	Xuanwu Hospital, Captial Medical University	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Capital Medical University

Country where clinical trial is conducted

China, 

References & Publications (9)

Cai L, Stevenson J, Geng X, Peng C, Ji X, Xin R, Rastogi R, Sy C, Rafols JA, Ding Y. Combining Normobaric Oxygen with Ethanol or Hypothermia Prevents Brain Damage from Thromboembolic Stroke via PKC-Akt-NOX Modulation. Mol Neurobiol. 2017 Mar;54(2):1263-1277. doi: 10.1007/s12035-016-9695-7. Epub 2016 Jan 28. — View Citation

Ding J, Zhou D, Sui M, Meng R, Chandra A, Han J, Ding Y, Ji X. The effect of normobaric oxygen in patients with acute stroke: a systematic review and meta-analysis. Neurol Res. 2018 Jun;40(6):433-444. doi: 10.1080/01616412.2018.1454091. Epub 2018 Mar 30. Review. — View Citation

Fujiwara N, Mandeville ET, Geng X, Luo Y, Arai K, Wang X, Ji X, Singhal AB, Lo EH. Effect of normobaric oxygen therapy in a rat model of intracerebral hemorrhage. Stroke. 2011 May;42(5):1469-72. doi: 10.1161/STROKEAHA.110.593350. Epub 2011 Mar 17. — View Citation

Liang J, Qi Z, Liu W, Wang P, Shi W, Dong W, Ji X, Luo Y, Liu KJ. Normobaric hyperoxia slows blood-brain barrier damage and expands the therapeutic time window for tissue-type plasminogen activator treatment in cerebral ischemia. Stroke. 2015 May;46(5):1344-1351. doi: 10.1161/STROKEAHA.114.008599. Epub 2015 Mar 24. — View Citation

McCourt R, Gould B, Kate M, Asdaghi N, Kosior JC, Coutts S, Hill MD, Demchuk A, Jeerakathil T, Emery D, Butcher KS. Blood-brain barrier compromise does not predict perihematoma edema growth in intracerebral hemorrhage. Stroke. 2015 Apr;46(4):954-60. doi: 10.1161/STROKEAHA.114.007544. Epub 2015 Feb 19. — View Citation

Shi SH, Qi ZF, Luo YM, Ji XM, Liu KJ. Normobaric oxygen treatment in acute ischemic stroke: a clinical perspective. Med Gas Res. 2016 Oct 14;6(3):147-153. eCollection 2016 Jul-Sep. Review. — View Citation

Xu H, Li R, Duan Y, Wang J, Liu S, Zhang Y, He W, Qin X, Cao G, Yang Y, Zhuge Q, Yang J, Chen W. Quantitative assessment on blood-brain barrier permeability of acute spontaneous intracerebral hemorrhage in basal ganglia: a CT perfusion study. Neuroradiolo — View Citation

Xu Q, Fan SB, Wan YL, Liu XL, Wang L. The potential long-term neurological improvement of early hyperbaric oxygen therapy on hemorrhagic stroke in the diabetics. Diabetes Res Clin Pract. 2018 Apr;138:75-80. doi: 10.1016/j.diabres.2018.01.017. Epub 2018 Feb 3. — View Citation

You P, Lin M, Li K, Ye X, Zheng J. Normobaric oxygen therapy inhibits HIF-1a and VEGF expression in perihematoma and reduces neurological function defects. Neuroreport. 2016 Mar 23;27(5):329-36. doi: 10.1097/WNR.0000000000000542. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The proportion of death or major disability		90 days after the onset
Secondary	The change in the midline shift from the initial to follow-up CT/MRI scans		Day0, Day1,Day3,Day7,Day14
Secondary	The change in the volume of ICH from the initial to follow-up CT/MRI scans		Day0, Day1,Day3,Day7,Day14
Secondary	The change of cerebral blood flow in perihematomal lesions follow-up CTP scans		Day0, Day1,Day7
Secondary	The evaluation of neurological impairment caused by a stroke	National Institute of Health stroke scale(NIHSS),The score ranges from 0 to 42. The higher the score, the more severe the nerve damage.	Day0, Day1,Day3,Day7,Day90
Secondary	Neurological function outcome	The modified Rankin scale is used to measure the recovery of neurological function in patients after stroke. The score range is from 0 to 5. The higher the score, the worse the neurological function is restored. We need to calculate the proportion of the modified Rankin scale 0-2.	Day90
Secondary	The evaluation of serum biomarkers	We used ELISA kits to detect the lebvels of neuron - specific enolase (NSE) , matrix metalloprotease 9 (MMP-9), reactive oxygen species (ROS) and hypoxia-inducing factor 1a (HIF-1a) in blood. The results were measured in ng/ml.	Day0, Day1,Day3,Day7,Day14