Pilot study to assess the efficacy of oral Lamivudine for macular edema due to retinal vein occlusions
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Mean change from baseline in Best-corrected visual acuity (BCVA) [ Time Frame: Baseline to Week 12]. Assessed with Early treatment diabetic retinopathy study (ETDRS) visual acuity testing charts at baseline and Weeks 2,4,8 and 12.
研究概览
简要总结
Introduction:
The most visually threatening complications of retinal vein occlusions include macular edema and neovascularisation. The predominant management of macular edema consists of intravitreal anti-VEGF injections which cause a reduction in macular thickness, which is well demonstrated on Spectral Domain - Optical Coherence Tomography (SD-OCT). In this study, we attempt to study the efficacy and safety of orally administered lamivudine in causing a reduction in macular edema secondary to retinal vein occlusion.
Review of Literature:
Lamivudine is a Nucleoside Reverse Transcriptase Inhibitor (NRTI) being used to control disease activity in People Living with HIV/AIDS (PLHA). Studies have demonstrated anti-inflammatory as well as anti-angiogenic activity of drugs used to treat HIV, including Lamivudine. Lamivudine weakens ERK (extracellular signal regulated kinases) phosphorylation promoted in endothelial cells by VEGF-A. It also depresses VEGF - promoted AKT phosphorylation in endothelial cells. Inhibition of angiogenesis and lymphangiogenesis in endothelial cell line was also studied, leading the authors to conclude that NRTIs negatively regulate angiogenesis and lymphangiogenesis. Since endothelial dysfunction is the cause of macular edema in retinal vein occlusions, we aim to study if orally administered lamivudine can be used for its treatment.
Justification for the study:
The standard of care for macular edema secondary to retinal vein occlusions is intravitreal injection of anti- VEGF agents. This procedure needs sterile operation theatre condition, driving up costs for both the hospital and the patient. Substituting intravitreal injections with oral tablets would reduce costs involved as well as remove attendant risks associated with an invasive procedure such as endophthalmitis.
Major objective:
To test safety and efficacy of oral lamivudine as treatment for macular edema secondary to retinal vein occlusion and compare outcomes with intravitreal bevacizumab (Avastin) injection for the same indication.
Materials and Methods:
-Pilot interventional single center trial
-Treatment duration: 1 month. After obtaining informed consent, patients clinically diagnosed with retinal vein occlusion and noted to have foveal center - involved macular edema secondary to the RVO, retinal thickness in the central subfield >350 microns as measured by OCT, and visual acuity between 6/12 and 6/60 in the study eye will be recruited. Patients will be administered oral lamivudine 150mg twice daily.
-Primary outcome measures to be measured at the end of 1 month, include best corrected visual acuity and macular edema resolution to be determined by OCT. Safety outcomes include the number of participant withdrawals, number and severity of systemic and ocular toxicities and the number of adverse events.
Risks and Benefits:
- most common adverse events include nausea, dizziness, fatigue, malaise, headache, dreams, insomnia and skin rash. Laboratory abnormalities are uncommon with lamivudine.
-possible benefits include resolution of macular edema.
Expected Outcome:
Systemic treatment (oral) for the management of retinal vein occlusion induced macular edema.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 盲法
- Investigator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 75.00 Year(s)（—）
- 性别
- All
入选标准
- •patients with documented presence of intraretinal or subretinal fluid secondary to Retinal Vein Occlusion.
- •patients with ability and willingness to comply with treatment and follow up process and to understand and sign the informed consent form.
排除标准
- •Study Eye only: 1)Evidence of iris, anterior chamber angle or retinal/optic disc neovascularization 2)Ocular disorders/additional eye disease, which in the opinion of the Investigator may confound interpretation of study results, compromise protocol assessments or are likely to require intervention during the study, including, but not limited to, atrophy of the retinal pigment epithelium, sub-retinal fibrosis, organized hard exudate plaque, clinically significant diabetic macular edema, retinal detachment, macular hole, vitreomacular traction, macular epiretinal membrane, clinically significant cataract, vitreal opacities or hemorrhage, glaucoma with documented visual field loss, ischemic optic neuropathy, retinitis pigmentosa or choroidal neovascularization of any cause (e.g., Age-related Macular Degeneration (AMD), ocular histoplasmosis, toxoplasmosis, or pathologic myopia) 3)Receipt within the past 6 months prior to the Screening Visit of any intraocular or periocular surgery (including refractive surgery, cataract surgery), or intravitreal (IVT) injection, or planned intraocular surgery or procedure during the study Both Eyes: 1)History of glaucoma or an IOP greater than 21 mmHg 2)Previous use of intraocular or periocular steroids within 3 months prior to baseline, or dexamethasone intravitreal implant within 6 months prior to baseline 3)History of, or presence of uveitis, presence of intraocular inflammation 4)History of intravitreal use of anti-VEGF drugs (e.g. ranibizumab，bevacizumab，aflibercept,etc), macular laser photocoagulation (focal/grid)，panretinal laser photocoagulation, vitrectomy, trabeculectomy or keratoplasty in the study eye at any time prior to baseline.
- •YAG laser treatment or any other intraocular surgeries (e.g. cataract surgery) in the study eye within 6 months prior to the baseline 5)Within 6 months prior to the Screening Visit, use of medications known to be toxic to the retina, lens, or optic nerve (e.g., desferoxamine, chloroquine/hydrochloroquine, chlorpromazine, phenothiazines, tamoxifen, and ethambutol).
- •History of impaired renal or liver function 7)Liver dysfunction (ALT or AST is 2 times higher than the upper limit of normal value in the local laboratory).
- •Renal function impairment (Cr is 1.5 times higher than the upper limit of normal values in the local laboratory) 8)Women in pregnancy and lactation 9)Individuals with HIV, HBV, or who have current/previous use of Nucleoside Reverse Transcriptase Inhibitors (NRTIs) or non-NRTIs.
结局指标
主要结局
Mean change from baseline in Best-corrected visual acuity (BCVA) [ Time Frame: Baseline to Week 12]. Assessed with Early treatment diabetic retinopathy study (ETDRS) visual acuity testing charts at baseline and Weeks 2,4,8 and 12.
时间窗: baseline, 2 weeks, 4 weeks, 8 weeks, 12 weeks
次要结局
- Mean change from baseline Center Subfield Macular Thickness (CMT). [ Time Frame: Baseline to Week 12]. Assessed with Spectral Domain Optical Coherence Tomography (SD-OCT) at baseline and Weeks 2,4,8 and 12.(baseline, 2 weeks, 4 weeks, 8 weeks, 12 weeks)
- Change from baseline in Foveal Avascular Zone (FAZ) and Vessel Density (VD). [ Time Frame: Baseline to Week 12]. Assessed with Optical Coherence Tomography Angiography (OCTA) at baseline and Weeks 2,4,8 and 12(baseline, 2 weeks, 4 weeks, 8 weeks, 12 weeks)
- Macular Function Using multi-focal electroretinogram (mf-ERG) [ Time Frame: baseline to 12 weeks ] To determine if there is a change in central amplitude responses using mfERG at 12 weeks compared to baseline values(baseline, 12 weeks)
- Mean change from baseline in contrast sensitivity. [ Time Frame: Baseline to Week 12]. Assessed with MARS Contrast sensitivity test at baseline and Weeks 2,4,8 and 12.(baseline, 2 weeks, 4 weeks, 8 weeks, 12 weeks)
- Safety - laboratory parameters [ Time Frame: 12 weeks] assessed by Liver and Renal function tests at baseline and week 12.(baseline, 12 weeks)
研究者
Dr Siddharth Narendran
Aravind Eye Hospital, Coimbatore