A Pilot study to assess the efficacy of Oral Lamivudine for Diabetic Macular Edema
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Mean change from baseline in Best-corrected visual acuity assessed with Early treatment diabetic retinopathy study (ETDRS) visual acuity testing chart
研究概览
简要总结
Introduction:
As the prevalence of diabetes mellitus increases worldwide, diabetic retinopathy(DR) has grown in global significance as a major cause of vision loss. Diabetic macular edema(DME) is a common vision threatening form of DR that develops in approximately 20% of diabetic patients within 15 years following the diagnosis of diabetes and when untreated , culminates in progressive central vision loss with time. While pathophysiological processes leading to DME are incompletely understood, it is clear that the pathology extends beyond a pure microvasculopathy to include other factors such as inflammatory mechanisms like inflammasome activation.
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 has been shown in mouse models to have a protective effect against the development of the vascular effects of diabetic retinopathy. Health insurance database analyses have shown that both HIV- negative and HIV - positive patients taking NRTIs have a reduced risk of developing type 2 diabetes. Importantly, the safety profile of Lamivudine is well established in both children and adults , making it a promising candidate for further investigation in this new therapeutic context.
Justification for the study:
The standard of care for diabetic macular edema is intra-ocular, specifically, intravitreal injection of anti-VEGF agents such as bevacizumab/ ranibizumab/ aflibercept. This procedure needs sterile operation theatre conditions, 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 diabetic macular edema and compare outcomes with intravitreal bevacizumab(avastin) injected for the same indication.
Study design:
Randomized , placebo- controlled, single blinded clinical trial .
Patients will be randomly assigned to one of two groups:
-
Lamivudine group: Patients will receive oral lamivudine at a dose of 150mg twice daily.
-
Placebo group: Patients will receive no treatment
Follow up and intervention:
At the end of weeks 4,8 and 12 , participants from both the groups will receive loading doses of intravitreal Avastin. This phase will continue for the next three months following the initial 12- week period.
Risk 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 , also, possible approval of lamivudine as an oral drug for controlling diabetic macular edema.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- None
入排标准
- 年龄范围
- 18.00 Year(s) 至 75.00 Year(s)（—）
- 性别
- All
入选标准
- •Patient age of 18 years or older 1)BCVA of ≥ 24 and ≤ 73 letters (20/40 or worse but at least 20/320) by an ETDRS chart. BCVA of the non-study eye must be no worse than 20/400 Snellen equivalent) 2)Diagnosis of diabetes mellitus, type 1 or 2 with non-proliferative or non-high risk proliferative diabetic retinopathy. Any one of the following will be considered sufficient evidence that diabetes is present: Current regular use of insulin for the treatment of diabetes Current regular use of oral hypoglycemic agents for the treatment of diabetes 3)DME based on investigator’s clinical evaluation and demonstrated on fundus photographs, fluorescein angiograms, and/or spectral domain-optical coherence tomography (SD.
- •OCT) 4)Mean foveal thickness of at least 325 μm by SD.
- •OCT 5)Ability and willingness to comply with the treatment and follow up procedures 6)Ability to understand and sign the informed consent form 7)Intraocular pressure of ≤ 21 mm Hg on 2 or fewer IOP lowering medications.
排除标准
- •Pregnant patients, currently lactating patients, or females of childbearing potential (unless using reliable contraception such as double barrier, surgical sterilization, oral contraceptives, intrauterine device (IUD), etc.
- •Body weight less than 55 kg 3)Allergy or hypersensitivity (known or suspected) to fluorescein or any component of the investigational product or delivery system 4)Any ocular surgery in the study eye within 12 weeks of screening 5)Any history of vitrectomy in the study eye 6)Aphakia in the study eye 7)Presence of severe foveal ischemia 8)Prior intraocular or periocular treatment for Diabetic macular edema 9)Macular laser for the treatment of diabetic macular edema within 12 weeks of screening 10)Any change in systemic steroidal therapy within 3 months of screening 11)Retinal or choroidal neovascularization due to ocular conditions other than diabetic retinopathy 12)History or presence of viral disease of the cornea or conjunctiva including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, varicella, any mycobacterial infections of the eye, or any fungal disease of any ocular structure or history of infectious retinitis 13)History or presence of any disease or condition that in the investigator’s opinion would preclude study treatment or follow-up or that in the opinion of the investigator would render them as unlikely to benefit from study treatment 14)Any lens or corneal opacity which impairs visualization of the posterior pole 15)Participation in another clinical trial within 12 weeks before the screening visit or during the study 16)History of any clinically significant medical disorders the principal investigator considers exclusionary, including (but not limited to), neuromuscular, hematological disease, immune deficiency state, respiratory disease, hepatic or gastrointestinal disease, neurological or psychiatric disease, neoplastic disease, renal or urinary tract diseases, or dermatological disease 17)History or current evidence of hypersensitivity to any components of the study medication, as assessed by the investigator 18)Participation in any systemic experimental treatment or any other systemic investigational new drug within 6 weeks or 5 half-lives of the active ingredient (whichever is longer) prior to the start of study treatment.
- •Clinical trials solely involving observation, over-the-counter vitamins, supplements, or diets are not exclusionary 19)Expectation that subject will be moving away from the area of the clinical treatment center without the ability to return for visits within the study period.
结局指标
主要结局
Mean change from baseline in Best-corrected visual acuity assessed with Early treatment diabetic retinopathy study (ETDRS) visual acuity testing chart
时间窗: at baseline and weeks 4,8,12,16,20 and 24
次要结局
- Mean change from baseline Center Subfield Macular Thickness (CMT).(Assessed with Spectral Domain Optical Coherence Tomography (SD-OCT))
- Change from baseline in Foveal Avascular Zone (FAZ) and Vessel Density (VD)(Assessed with Optical Coherence Tomography Angiography (OCTA))
研究者
Dr Siddharth Narendran
Aravind Eye Hospital, Coimbatore