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Chronic Cerebral IschemiaPhase 2/3NCT03105141

Optimized Remote Ischemic Conditioning (RIC) Treatment for Patients With Chronic Cerebral Ischemia

A Phase 2/3 study testing Remote ischemic conditioning in people with Chronic Cerebral Ischemia and Intracranial Atherosclerosis, run by Capital Medical University at 2 sites in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial summary

This prospective, randomized, single-center clinical trial is designed to figure out the most optimal algorithm of remote ischemic conditioning on patients with chronic cerebral ischemia. Read more about this study

Who is it for?
Ages 40 to 80 years
What is being tested?
Remote ischemic conditioning
Type of treatment
Medical device
Could I receive a placebo?
No, everyone receives an active treatment
How many people
600 participants
Where
2 sitesChina
Study dates
1 Jun 2017to Jan 2020
Phase
Phase 2/3
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 40 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 1. Age ranging from 45 to 80 years of age, both genders;
  • 2. Patients diagnosed with an ischemic stroke or TIA before admission and the following requirements should be satisfied as well:
  • The occurrence of an ischemic stroke within 30 days and with a baseline modified Rankin Scale (mRS) score≤4.
  • The occurrence of an TIA within 15 days and with a baseline Oxfordshire Community Stroke Project on the basis of age, blood pressure (BP), clinical features, and duration of TIA symptoms (ABCD2) score≥4.
  • 3. Patients with symptomatic intracranial atherosclerotic stenosis (sIAS) that is attributed to at least 50% stenosis of the diameter of a major intracranial artery (carotid artery, or middle cerebral artery (M1)) verified by magnetic resonance angiography (MRA) or computed tomographic angiography (CTA).
  • 4. Informed consent obtained patients or health care proxy, as appropriate, able to cooperate and participate follow-up visits.

Who cannot join

  • 1. Received intravenous or intraarterial thrombolytic therapy such as recombinant tissue plasminogen activator (rtPA) within 24 hours prior to inclusion.
  • 2. Progressive deterioration of neurological manifestations within 24 hours prior to inclusion.
  • 3. Intracranial arterial stenosis due to any of the following non-atherosclerotic etiologies, for instance, moyamoya disease, artery dissection, any known vasculitic disease, any intracranial infection, radiation induced vasculopathy, cerebrospinal fluid (CSF) pleocytosis associated intraarterial stenosis, genetic or developmental abnormalities such as fibromuscular dysplasia, neurofibromatosis, sickle cell disease, and mitochondrial encephalopathy, intracranial granulomatous arteritis, postpartum angiopathy, suspected vasospasm or embolism, iatrogenic trauma.
  • 4. Intracranial abnormalities such as tumor, abscess, vascular malformation, cerebral venous sinus stenosis or thrombosis.
  • 5. Any hemorrhagic transformation or large area of cerebral infarction (more than 1/3 of middle cerebral artery perfusion territory).
  • 6. Any type of intracranial hemorrhage within 90 days prior to inclusion.
Show all 23Show fewer
  • 7. Potential cardiac source of embolism such as rheumatic mitral and or aortic stenosis, prosthetic heart valves, atrial flutter, atrial fibrillation, left atrial myxoma, sick sinus syndrome, patent foramen ovale, left ventricular mural thrombus or valvular vegetation, congestive heart failure, and bacterial endocarditis.
  • 8. Previous stent, angioplasty, or other mechanical device in the target lesion, or plan to receive any of the above procedures within 12 months after inclusion.
  • 9. Refractory hypertension (systolic blood pressure (SBP) >180 mmHg; diastolic blood pressure (DBP) >110 mmHg) that cannot be controlled by medical intervention.
  • 10. Above 50% stenosis of extracranial artery (carotid artery or vertebral artery).
  • 11. Above 50% stenosis of subclavian artery or subclavian steal syndrome.
  • 12. Retinal hemorrhage or visceral bleeding within 30 days prior to inclusion.
  • 13. Myocardial infarction within previous 30 days prior to inclusion.
  • 14. Previous history of major surgery within 30 days prior to inclusion, or arranged for any of the procedure within 12 months after inclusion.
  • 15. Severe hemostatic or coagulation disorders (Haemoglobin <10 g/dL, blood platelet count < 100 × 109/L).
  • 16. Hepatic or renal dysfunctions (aspartate transaminase (AST) and/or alanine transaminase (ALT) >3×upper limit of normal range, creatinine clearance <0.6 ml/s and/or serum creatinine >265 μmol/l (>3.0 mg/dl)).
  • 17. Current or having a history of chronic physical diseases or mental disorders.
  • 18. Life expectancy < 3 years due to concomitant life-threatening illness.
  • 19. Contraindications for remote ischemic conditioning: significant peripheral arterial disease, soft tissue or vascular injury, wounds, and fracture affecting the upper limbs.
  • 20. Pregnant or lactating women.
  • 21. Patients unlikely to be compliant with intervention or return for follow-up visits.
  • 22. No consent obtained from the patient or available legally authorized representatives.
  • 23. Patients recruited into another clinical investigation with medication or device, which is likely to impact the outcome of this study.

Trial locations and contacts

2 sites in 1 country.

Ran Meng, MD, PhD contact

+86-10-83198952

Ranmeng2011@pku.org.cn

Da Zhou, MD, PhD Candidate contact

+86-10-83198952

popdoctor@foxmail.com

China2 sites, 2 recruiting

  • Xuanwu Hospital, Capital Medical University

    Beijing, Beijing Municipality, 100053

    Xunming Ji

    Xunming Ji

    Recruiting

  • Xuanwu Hospital, Capital Medical University

    Beijing, 100053

    Ran Meng, MD, PhD, +86-10-83198952, Ranmeng2011@pku.org.cn

    Da Zhou, MD, PhD Candidate, +86-10-83198952, popdoctor@foxmail.com

    Recruiting

Other trials in China

About this study

Official title: The Impact of Repeated Bilateral Limb Remote Ischemic Conditioning on Patients With Chronic Cerebral Ischemia: Establishment of Optimized Algorithm on the Basis of Feasibility, Safety and Efficacy

This prospective, randomized, single-center clinical trial is designed to figure out the most optimal algorithm of remote ischemic conditioning on patients with chronic cerebral ischemia.

Read the detailed description

Chronic cerebral ischemia (CCI) refers to a prevalent pathophysiological condition in which cerebral hypoperfusion is caused by a reduction in cerebral blood flow over a long period of time. CCI, as a consequence of intracranial atherosclerotic stenosis (ICAS) has been identified as one of the major culprits that are responsible for occurrence/recurrence of acute cerebrovascular accidents such as ischemic stroke and transient ischemic attack, as well as vascular cognitive dysfunction. The prevalence of ICAS related CCI among stroke patients is remarkably higher in the Chinese population than in the whites, and there are no quite effective therapies for the general patient population with ICAS up to now. Endovascular intervention appears to be a promising option for a group of patients with severe ICAS, but may not be applicable for those with certain vascular risk features that are supposed to increase the rate of complications or result in unsatisfactory clinical outcomes. In addition, high cost and adverse effects of medications pose huge burdens to patients, their families and even the whole society as well.

RIC is a novel therapeutic approach whereby repetitive, transient, non-lethal ischemia intervened by reperfusion employed on a distant organ or tissue confers protection to targeted organs against subsequent major ischemic attack. Preclinical experimental studies have demonstrated the neuroprotective effects of RIC in ischemic stroke models. Meanwhile, small-scale, proof of concept clinical trials revealed that long-term RIC was able to lower the stroke recurrence and enhance the cerebral reperfusion, without inducing adverse events in patients with ICAS. Nevertheless, current protocol of RIC utilited in this scenario was mainly based on previous animal studies or cardiovascular clinical trials. Whether modifying the ischemic pressure, numbers of cycles, duration of ischemia as well as the method for application can lead to different outcomes remain to be settled. In this study, 600 patients satisfied with the inclusion criteria will be recruited and randomly allocated into four substudies to receive RIC treatment (Doctormate®) under different algorithms. The most optimal algorithm of RIC on patients with ICAS related CCI would be determined according to clinical endpoints. Other medical managements are guaranteed based on the best medical judgment from clinical practitioners.

Being tested
Remote ischemic conditioning
Keywords
Intracranial atherosclerotic stenosis, Remote ischemic conditioning, Stroke
Medical subject headings
Intracranial Arteriosclerosis, Stroke

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Remote ischemic conditioningDevice

    Remote ischemic conditioning is composed of 5 cycles of 5-min bilateral upper limb ischemia intervened by 5-min reperfusion, which is induced by an automated cuff-inflator (Doctormate®) placed on both upper arms and inflated to a given pressure followed by deflation, twice daily for 12 months.

    Two different magnitude of limb ischemia pressure will be set: 200 mmHg and 40 mmHg above systolic pressure (60 patients for each).

    Optimal inflating pressure will be determined based on the results.

  • Remote ischemic conditioningDevice

    Remote ischemic conditioning is composed of a given cycle of 5-min bilateral upper limb ischemia intervened by 5-min reperfusion, which is induced by an automated cuff-inflator (Doctormate®) placed on both upper arms and inflated to 200 mmHg pressure followed by deflation, twice daily for 12 months.

    The number of cycles of limb ischemia will be set as: 4, 5 and 6 (60 patients for each).

    Optimal cycles for application will be determined based on the results.

  • Remote ischemic conditioningDevice

    Remote ischemic conditioning is composed of 5 cycles of a given duration of bilateral upper limb ischemia intervened by reperfusion, which is induced by an automated cuff-inflator (Doctormate®) placed on both upper arms and inflated to 200 mmHg pressure followed by deflation, twice daily for 12 months.

    The duration of each cycle for limb ischemia will be set as: 4, 5 and 6-min (60 patients for each).

    Ischemia duration algorithm will be determined based on the results.

  • Remote ischemic conditioningDevice

    Remote ischemic conditioning is composed of 5 cycles of 5-min bilateral upper limb ischemia intervened by reperfusion, which is induced by an automated cuff-inflator (Doctormate®) placed on both upper arms and inflated to 200 mmHg pressure followed by deflation, once or twice daily for 12 months.

    The method for application will be set as: once daily for 12 months and twice daily for 12 months (60 patients for each).

Study groups in NCT03105141
Study groupRoleWhat they receive
RIC substudy 1ExperimentalA total of 120 patients in this substudy will receive standard medical therapy and bilateral upper limb remote ischemic conditioning intervention (Doctormate®) (200 mmHg or 40 mmHg above systolic pressure) twice daily for 12 months.
Receives: Device: Remote ischemic conditioning
RIC substudy 2ExperimentalA total of 180 patients in this substudy will receive standard medical therapy and bilateral upper limb remote ischemic conditioning intervention (Doctormate®) (200 mmHg) twice daily for 12 months.
Receives: Device: Remote ischemic conditioning
RIC substudy 3ExperimentalA total of 180 patients in this substudy will receive standard medical therapy and bilateral upper limb remote ischemic conditioning intervention (Doctormate®) (200 mmHg) twice daily for 12 months.
Receives: Device: Remote ischemic conditioning
RIC substudy 4ExperimentalA total of 120 patients in this substudy will receive standard medical therapy and bilateral upper limb remote ischemic conditioning intervention (Doctormate®) (200 mmHg) once or twice daily for 12 months.
Receives: Device: Remote ischemic conditioning

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Recurrent rate of ischemic stroke and/or transient ischemic attack

    Measured: baseline, within 12 months

Secondary outcomes (14)

  1. Treatment Related Adverse Events

    Signs of skin injury such as skin breakdown, edema, redness and ecchymosis; Signs of muscle injury such as tenderness and elevated serum plasma levels of muscle enzymes; Signs of neurovascular injury such as weak or lost distal radial pulse and abnormal electromyography (EMG); Systemic adverse events such as palpitation, headache, nausea and dizziness.

    Measured: within 12 months

  2. The incidence of composite vascular events

    Composite vascular events include ischemic or hemorrhagic stroke, myocardial infarction, transient ischemic attack, deep vein thrombosis and thromboembolism.

    Measured: within 12 months

  3. The incidence of each component of composite vascular events

    Composite vascular events include ischemic or hemorrhagic stroke, myocardial infarction, transient ischemic attack, deep vein thrombosis and thromboembolism.

    Measured: within 12 months

  4. The incidence of all cause mortality

    Death due to any reasons.

    Measured: within 12 months

  5. The evaluation of cognitive function

    Cognitive function will be assessed by mini-mental state examination (MMSE), the Montreal Cognitive Assessment (MoCA) and/or Modified Telephone Interview for Cognitive Status (TICS-M).

    Measured: baseline, within 3, 6 and 12 months

  6. The evaluation of neurological impairment caused by a stroke

    The neurological impairment caused by a stroke will be assessed by National Institutes of Health Stroke Scale (NIHSS).

    Measured: baseline, within 3, 6 and 12 months

  7. The evaluation of degree of disability or dependence in the daily activities

    The degree of disability will be assessed by modified Rankin Scale (mRS).

    Measured: baseline, within 3, 6 and 12 months

  8. The evaluation of performance in activities of daily living

    he performance in activities of daily living will be assessed by Barthel Index (BI) scale.

    Measured: baseline, within 3, 6 and 12 months

  9. Mean changes in cerebral blood perfusion and/or collateral circulation

    Cerebral blood perfusion and/or collateral circulation will be evaluated by Magnetic Resonance Angiography (MRA), Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), Computed Tomography Angiography (CTA), Arterial spin-labeled magnetic resonance imaging (ASL-MRI), Single Photon Emission Computed Tomography (SPECT), and Transcranial Cerebral Doppler (TCD).

    Measured: baseline, within 12 months

  10. Mean change in brain function

    Brain function will be evaluated by multimodal imaging modalities such as Magnetic Resonance Spectroscopy (MRS), Diffusion Tensor Imaging (DTI), Functional Magnetic Resonance Imaging (fMRI), Electroencephalography (EEG) and Near-infrared spectroscopy.

    Measured: baseline, within 12 months

  11. Changes in cerebral white matter lesions (WMLs)

    The characteristics of WMLs such as localization, volumetric progression and severity will be evaluated by conventional MRI (such as T2-weighted MR images) and non-conventional MRI (such as DTI).

    Measured: baseline, within 12 months

  12. The occurrence of additional neurological events

    Additional neurological events will be documented.

    Measured: within 12 months

  13. The evaluation of serum biomarkers

    A couple of selected serum markers for coagulation, fibrinolysis, vascular endothelial function and immunological, anti-oxidant, as well as apoptotic pathways will be assessed.

    Measured: baseline, within 1, 3, 6 and 12 months

  14. Number of participants with abnormal lab values

    Lab examinations such as hepatic, renal function, blood and urine routine will be documented.

    Measured: baseline, within 1, 3, 6 and 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Apr 2017
  2. Study start1 Jun 2017
  3. Primary completionApr 2019 (estimated)
  4. Study completionJan 2020 (estimated)

Resources

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 2/3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Care provider, Outcomes assessor
Enrolment
600 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03105141
Sponsor's protocol ID
RIC2017-CCI
Status last verified
Dec 2017
First submitted
2 Apr 2017
Last updated
5 Dec 2017
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Meng R, Asmaro K, Meng L, Liu Y, Ma C, Xi C, Li G, Ren C, Luo Y, Ling F, Jia J, Hua Y, Wang X, Ding Y, Lo EH, Ji X. Upper limb ischemic preconditioning prevents recurrent stroke in intracranial arterial stenosis. Neurology. 2012 Oct 30;79(18):1853-61. doi: 10.1212/WNL.0b013e318271f76a. Epub 2012 Oct 3.

    PubMed 23035060

  • Meng R, Ding Y, Asmaro K, Brogan D, Meng L, Sui M, Shi J, Duan Y, Sun Z, Yu Y, Jia J, Ji X. Ischemic Conditioning Is Safe and Effective for Octo- and Nonagenarians in Stroke Prevention and Treatment. Neurotherapeutics. 2015 Jul;12(3):667-77. doi: 10.1007/s13311-015-0358-6.

    PubMed 25956401

  • Wang Y, Zhao X, Liu L, Soo YO, Pu Y, Pan Y, Wang Y, Zou X, Leung TW, Cai Y, Bai Q, Wu Y, Wang C, Pan X, Luo B, Wong KS; CICAS Study Group. Prevalence and outcomes of symptomatic intracranial large artery stenoses and occlusions in China: the Chinese Intracranial Atherosclerosis (CICAS) Study. Stroke. 2014 Mar;45(3):663-9. doi: 10.1161/STROKEAHA.113.003508. Epub 2014 Jan 30.

    PubMed 24481975

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Remote ischemic conditioning in people with Chronic Cerebral Ischemia and Intracranial Atherosclerosis, run by Capital Medical University at 2 sites in China.

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 6 inclusion and 23 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 5 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in China. 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.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

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 Ran Meng, MD, PhD (+86-10-83198952, Ranmeng2011@pku.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Recurrent rate of ischemic stroke and/or transient ischemic attack (time frame: baseline, within 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 NCT03105141, which also lists 3 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 5 Dec 2017.

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