Multiple Burrhole Therapy With Erythropoietin for Unstable Moyamoya

Feasibility Study of Multiple Burrhole Therapy Combined With Intravenous Erythropoietin Pretreatment for Unstable Moyamoya

In this study, the investigators aim to evaluate the indirect revascularization outcomes of a new combination therapy of multiple burrhole procedure with promotion of arteriogenesis by intravenous (IV) erythropoietin (EPO) pretreatment on Moyamoya patients with acute neurological presentation, and outline the clinical and vascular factors associated with revascularization through the burrholes.

Study Overview

• Status: Completed
• Conditions: Ischemic Stroke; Moyamoya Disease; Angiogenesis; Ischemic Attack; Burr Hole
• Intervention / Treatment: Drug: erythropoietin

Detailed Description

This is a investigator led, single-center, single arm, interventional trial in prospective Moyamoya disease (MMD) and Moyamoya syndrome (MMS) registry. MMD or MMS patients with acute neurological presentation such as ischemic stroke or transient ischemic attack are eligible.

After inclusion, initial evaluation including transfemoral angiography is performed. A 3 day pre-procedure IV erythropoietin (120000 international units[IU] #3) is given for promotion of arteriogenesis, than multiple burrhole procedure is performed. Arteriogenesis is evaluated by 6 month transfemoral angiography.

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Gyunggido
    • Suwon, Gyunggido, Korea, Republic of
      • Ajou University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥16 years
• Acute neurological presentation with recurrent transient ischemic attacks (TIA) or cerebral infarction within 30 days of symptom onset
• Angiographic findings compatible with the diagnostic criteria for MMD or MMS (unilateral findings, bilateral distal internal carotid artery involvement without Moyamoya vessels, or presence of other causative factors)
• Significant decrease in basal perfusion and reservoir capacity on brain perfusion CT or Brain single photon emission computed tomography with acetazolamide (Diamox®) challenge (D-SPECT)

Exclusion Criteria:

• Definite presence of transdural collateral flow on cerebral angiography.
• Sufficient perfusion status via Willisian, leptomeningeal, or other collateral systems, as evaluated by multimodal imaging methods.
• > 30 days after symptom onset

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: multiple burrhole therapy and erythropoietin; pretreatment with IV erythropoietin for 3 days, 120000IU#3 then multiple burrhole procedure on the hemisphere effected is performed

Drug: erythropoietin; Epokine®, CJ healthcare, South Korea is used preprocedurally to promote revascularization. Total 120,000 units of EPO is injected for three consecutive days, 40,000 units mixed in IV saline 100 ml over 1 hour. The multiple burrhole procedure is performed in area of hemodynamic insufficiency by D-SPECT. It is performed under local anesthesia.; Other Names: multiple burrhole procedure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional status of the participants after 6 months of procedure assessed by modified Rankin Scale.	The functional status of participants will be assessed based on modified Rankin Scale for evaluation of feasibility of procedure.	6 month post-procedure
transdural arteriogenesis	the extent of collateral flow that has developed from external carotid artery to internal carotid artery through the burrholes	6 month post-procedural cerebral angiography

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	periprocedural and post-procedural complications	Any complications occuring within <14 days of burrhole procedure + erythropoietin is classified as periprocedural complications. Any complications occuring or detected after 14 days of procedure up to 6 months will be classified as post-procedural.

Collaborators and Investigators

• Sponsor: Ajou University School of Medicine
• Investigators: Principal Investigator: Ji Man Hong, Assistant Professor of Neurology

Publications and helpful links

General Publications

• Hong JM, Lee SJ, Lee JS, Choi MH, Lee SE, Choi JW, Lim YC. Feasibility of Multiple Burr Hole With Erythropoietin in Acute Moyamoya Patients. Stroke. 2018 May;49(5):1290-1295. doi: 10.1161/STROKEAHA.117.020566. Epub 2018 Apr 6.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2010
• Primary Completion (Actual): September 30, 2016
• Study Completion (Actual): September 30, 2016

Study Registration Dates

• First Submitted: May 18, 2017
• First Submitted That Met QC Criteria: May 19, 2017
• First Posted (Actual): May 22, 2017

Study Record Updates

• Last Update Posted (Actual): June 20, 2017
• Last Update Submitted That Met QC Criteria: June 19, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arterial Occlusive Diseases; Carotid Artery Diseases; Stroke; Cerebral Arterial Diseases; Intracranial Arterial Diseases; Ischemic Stroke; Ischemia; Moyamoya Disease; Hematinics; Epoetin Alfa
• Other Study ID Numbers: AJIRB-MED-T12-11-065

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No