The Neuroprotective Effect of PEG-GCSF in the Traumatic Optic Neuropathy

NCT ID: NCT06168188

Last Updated: 2023-12-13

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-24
• Study Completion Date: 2024-12-31

Brief Summary

The clinical trial will be a phase 1, semi-experimental trial, which will be performed in Hualien Tzu Chi Hospital. Twenty patients will be recruited in this study starting from the 2nd year of the project to the 3rd year of the project and will go through comprehensive eye and systemic examination in the Hualien Tzu Chi Hospital. Indirect TON (ITON) patients are defined as reduced best corrected visual acuity (BCVA), visual field, color vision, and positive relatively afferent pupillary defect (RAPD) with normal fundus and optic nerve examination and no evidence of direct trauma to optic nerve on spiral orbital and optic canal computer tomography (CT) scan. Therefore, all patients will have examinations of BCVA, visual field, color vision, RAPD, FVEP, CT scan, and IOP for defining ITON patients one day before Neulasta injection. Patient also underwent renal function test, liver function test, coagulation test, and complete blood count before the treatment. Patients who meet the enrollment criteria (inclusion and exclusion) will be fully informed of this treatment and then an informed consent will be obtained. After patient enrolment, the patient will be intravitreally administrated by 0.15 mL of Neulasta in the injured eye. Firstly, the injured eye will be treated with iodine solution for disinfection and then will be treated with Alcaine eye drop for topic anesthesia. The 0.15 mL of Neulasta will be filled into 1 mL of syringe equipped with 30 gauge beveled needle for intravitreal injection. During injection of Neulasta solution, the anterior chamber decompression will be performed for IOP balance. The aqueous humor from anterior chamber will be collected for further microarray analysis. After Neulasta treatment, Tobradex eyedrops (Alcon) will be given on the injected eye, four times a day. Patient will be hospitalized for one day to monitor BCVA, IOP, fundus condition, complete blood count, and any adverse event. During 3-month follow-up trial, each patient will be regularly monitored 7 days and 1, 3 months after treatments by determining the BCVA, the RPAD, the color vision, visual field, the latency of P-100 wave in FVEP, and the RNFL thickness, IOP, and complete blood count.

Conditions

Traumatic Optic Neuropathy

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Neulasta

The 0.15 mL of Neulasta will be filled into 1 mL of syringe equipped with 30 gauge beveled needle for intravitreal injection.

Group Type: EXPERIMENTAL

Neulasta® (pegfilgrastim)

Intervention Type: DRUG

Intravitreal injection of Neulasta® (pegfilgrastim) after TON

Interventions

Neulasta® (pegfilgrastim)

Intravitreal injection of Neulasta® (pegfilgrastim) after TON

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. 20-70 years old

2. Having indirect traumatic optic neuropathy, one week to 4 weeks after trauma

3. Normal disc figure and macula appearance

4. Reduced BCVA (Snellen Chart, less than 20/200) or C-24 central visual field loss more than 10 dB (MD<-10 dB)

5. Color vision defect and positive RAPD

6. No evidence of direct trauma to ON on spiral orbital and optic canal computer tomography (CT) scan.

7. Normal IOP (10-21 mm Hg)

8. Normal blood coagulation (prothrombin time: 8~12s; partial thromboplastin time: 23.9 - 35.5 s; international normalized ratio: 0.85~1.15)

9. Adequate hematologic (absolute neutrophil count ≥1.5 × 109/L, hemoglobin ≥9 g/dL, platelets ≥80 × 109/L, and PT/PTT/INR ≤1.0 × upper limit of normal; ULN)

10. Adequate hepatic function (albumin ≥2.8 g/dL, serum bilirubin ≤2.0 mg/dL or ≤2 × ULN, and aspartate aminotransferase and alanine aminotransferase ≤5.0 × ULN)

11. Adequate renal function (Serum BUN: 6-22 mg/dl; serum creatinine: 0.7-1.5 mg/dl for men, 0.5-1.2 mg/dl for women)

12. No other cranial nerve injuries (cranial nerve examination, nerve number: 1, 3-12)

Exclusion Criteria

1. Having other injuries that effect on visual function

2. Direct optic neuropathy

3. No light perception

4. Pregnant and breast feeding women

5. Having malignancy

6. Sickle-cell disease

7. G-CSF allergic reaction

8. Acute infectious diseases

9. Benign Intracranial hypertension symptoms (1. papilledema in both eyes with no spontaneous venous pulsation 2. Increase of peripapillary nerve fiber layer thickness in OCT imaging)

10. Associated intracranial hemorrhage or severe skull fracture

11. History or evidence of any other clinically condition that, in the opinion of the investigator, would pose a risk to patient's safety or interfere with study procedures, evaluation, or completion:

1. Diabetic retinopathy, maculopathy

2. Uncontrolled hypertension

3. History of stroke and cardiovascular diseases

4. Glaucoma

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Buddhist Tzu Chi General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Rong-Kung Tsai

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation

Taipei, Not US Or Canada, Taiwan

Site Status: RECRUITING

Countries

Taiwan

Central Contacts

Yao-Tseng Wen, PhD

Role: CONTACT

Phone: 886-982208109

Email: ytw193@gmail.com

Yi-Ping Tsai

Role: CONTACT

Phone: 886-3-8561825

Email: pitsai123@gmail.com

Facility Contacts

Yao-Tseng Wen, PhD

Role: primary

Yi-Ping Tsai, MD

Role: backup

References

Liu PK, Wen YT, Lin W, Kapupara K, Tai M, Tsai RK. Neuroprotective effects of low-dose G-CSF plus meloxicam in a rat model of anterior ischemic optic neuropathy. Sci Rep. 2020 Jun 25;10(1):10351. doi: 10.1038/s41598-020-66977-9.

Reference Type: BACKGROUND

PMID: 32587280 (View on PubMed)

Wen YT, Huang TL, Huang SP, Chang CH, Tsai RK. Early applications of granulocyte colony-stimulating factor (G-CSF) can stabilize the blood-optic-nerve barrier and ameliorate inflammation in a rat model of anterior ischemic optic neuropathy (rAION). Dis Model Mech. 2016 Oct 1;9(10):1193-1202. doi: 10.1242/dmm.025999. Epub 2016 Aug 18.

Reference Type: BACKGROUND

PMID: 27538969 (View on PubMed)

Huang SP, Fang KT, Chang CH, Huang TL, Wen YT, Tsai RK. Autocrine protective mechanisms of human granulocyte colony-stimulating factor (G-CSF) on retinal ganglion cells after optic nerve crush. Exp Eye Res. 2016 Feb;143:132-40. doi: 10.1016/j.exer.2015.10.010. Epub 2015 Oct 28.

Reference Type: BACKGROUND

PMID: 26518178 (View on PubMed)

Tsai RK, Chang CH, Wang HZ. Neuroprotective effects of recombinant human granulocyte colony-stimulating factor (G-CSF) in neurodegeneration after optic nerve crush in rats. Exp Eye Res. 2008 Sep;87(3):242-50. doi: 10.1016/j.exer.2008.06.004. Epub 2008 Jun 17.

Reference Type: BACKGROUND

PMID: 18602391 (View on PubMed)

Other Identifiers

TCMF-EP 108-01

Identifier Type: -

Identifier Source: org_study_id