Integrative Liver-Targeted Therapy for Diabetic Macular Edema: Combining Tauroursodeoxycholate and Traditional Chinese Medicine.
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 69
- 试验地点
- 1
- 主要终点
- Change from baseline in macrophage-like cell density (cells/mm²).
研究概览
简要总结
Diabetic macular edema is seen in the later stages of diabetic retinopathy with current conventional therapies targeting local vascular dysfunction. These therapies provide transient improvement in vision and are often uncomfortable to persons with diabetic macular edema and financially burdensome. Diabetic macular edema, a complication of diabetes cannot be managed without addressing systemic inflammation. Liver metabolism and functions are implicated in diabetes and evidence suggests that hepatic metabolic dysfunctions are linked to the neuroinflammation and vascular dysfunctions observed in diabetic retinopathy. Nutraceutical supplements like Tauroursodeoxycholate (a bile acid) and modified Qi Ju Di Huang Wan (a traditional Chinese medicine formula) have been found to reduce hepatic and retinal oxidative stress, provide anti-apoptotic, anti-inflammatory, neuroprotective and hepatoprotective effects. This study will provide a non-invasive multi-targeted strategy for the management of diabetic macular edema.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 89 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age range 18-89 years
- •Clinical diagnosis of diabetic retinopathy with diabetic macular edema (defined as CST greater than 250 and presence of microglia/macrophages on OCT) with a visual acuity between 20/32 and 20/
- •Written informed consent is provided.
- •Males and females
- •Routine laboratory study results CBC and Diff with bilirubin, aspartate aminotransferase and/or alanine aminotransferase, and creatinine within normal limits.
排除标准
- •History of difficulty controlling diabetes or hypertension with changes in medication in the last 3 months.
- •Eye having undergone YAG capsulotomy in the last 3 months.
- •Having other ocular surgeries in the last 6 months (examples include but not limited to cataract surgery, scleral buckle, trabeculectomies, etc.).
- •All women of childbearing potential must have a negative urine pregnancy test at the Screening Visit and throughout the study. Sexually active women participating in the study must use a medically acceptable form of contraception if they are not trying to get pregnant.
- •Chronic infectious disease (e.g. HIV, HCV)
- •Positive urine β-hCG test day of visit or a serum-hCG test within 48 hours prior to the initiation of the study
- •Other ocular diseases or fundus diseases
- •Currently taking an anti-inflammatory medication (e.g. anti-inflammatory agents, glucocorticoids or other immune modulating medications);
- •Use of cyclooxygenase-2 (COX-2) inhibitors for < 6 months prior to study entry or dose changes after study entry. Limited as-needed use is permitted prior to study entry but not during the study.
- •Use of statins that cross the blood brain barrier such as atorvastatin will not be permitted during the study as they have been shown to reduce levels of pro-inflammatory cytokines.
- •Any degree of hepatic or renal insufficiency that in the investigator's judgement would pose a safety risk with TUDCA or mQJDHW.
- •Subjects who based on history or mental status examination have a significant risk of committing suicide, or who are homicidal or violent and who are in the Investigator's opinion in significant imminent risk of hurting others.
- •Subjects who have a medical condition that, in the investigator's opinion, would expose them to an increased risk of a significant adverse event or interfere with assessments of safety and efficacy during the course of the trial.
- •Subjects with a current known infection or who are acutely ill.
- •Subjects with an autoimmune disease (i.e., Lupus, Rheumatoid Arthritis).
- •Subjects with thyroid disorders unless euthyroid at screening.
- •Subjects with cancer not in remission.
- •Inability to attend scheduled study visits, plans for family relocation during the study, or any other criteria that the investigator may determine to be associated with inability to complete the study.
- •Limited mental capacity rendering the subject unable to provide written informed consent or comply with evaluation procedures.
- •History of recent alcohol or drug abuse or noncompliance with treatment or other experimental protocols.
- •Use of any investigational drug/ nutraceuticals within 30 days prior to the baseline visit.
研究组 & 干预措施
Control (placebo) Arm
Participants will receive capsules with no active ingredient twice daily for six months.
干预措施: placebo capsule (Drug)
Tauroursodeoxycholate (TUDCA) Arm
TUDCA is a bile acid that is available as a supplement. It has been found to provide protection in neuroinflammatory and neurodegenerative diseases. Evidence links it to reducing retinopathy in pre-clinical studies.
干预措施: Tauroursodeoxycholate (TUDCA) (Dietary Supplement)
Traditional Chinese medicine (mQJDHW) Arm
Participants in this arm will be administered a standard dose of mQJDHW capsules twice daily for six months. mQJDHW, is a popular traditional Chinese medicine (TCM) formula used by TCM practitioners for managing eye diseases. It has been found to improve ocular health in anterior chamber diseases, uveitis, optic neuropathies and diabetic retinopathy. The various components of this formula, Tribulus terrestris, Paeonia lactiflora, Lycium chinensis, Angelica sinensis, Chrysanthemum morifolium, Paeonia suffruticosa, Dioscorea japonica, Cornus officinalis, Rehmannia glutinosa, Haliotis spp, Alisma plantago-aquatica and Dioscorea oppositifolia, have been found to provide neuroprotection, hepatoprotection, and reduce oxidative stress and neuroinflammation. Available in literature is evidence of the beneficial roles of this formula to systemic and retinal health.
干预措施: Traditional Chinese Medicine (mQJDHW) (Dietary Supplement)
结局指标
主要结局
Change from baseline in macrophage-like cell density (cells/mm²).
时间窗: Up to three months
Optical coherence tomography (OCT) images will be taken at each visit to visualize macrophage-like cells (MLC) seen in persons with DME. OCT images will be taken at the study visits and changes in the MLC density will be measured.
Change from baseline in best-corrected visual acuity (ETDRS letters).
时间窗: Up to three months
Each participant will have their best corrected visual acuity measured by Early Treatment of Diabetic Retinopathy study (ETDRS) chart.
Change from baseline in serum neuroinflammatory makers.
时间窗: Up to three months
Blood will be drawn and neuroinflammatory and hepatic makers will be assessed at each study visit
Change from baseline in serum hepatic biomarkers.
时间窗: Up to three months
Blood will be drawn and hepatic makers will be assessed at each study visit.
Change in macrophage-like cell density.
时间窗: Up to three months
Optical coherence tomography (OCT) images will be taken at each visit to visualize macrophage-like cells (MLC) seen in persons with DME. OCT images will be taken at the study visits and changes in the MLC density will be measured.
Change in best corrected visual acuity.
时间窗: Up to three months
Each participant will have their best corrected visual acuity measured by Early Treatment of Diabetic Retinopathy study (ETDRS) chart.
Changes in neuroinflammatory and hepatic makers.
时间窗: Up to three months
Blood will be drawn and neuroinflammatory and hepatic makers will be assessed at each study visit
次要结局
- Change from baseline in macular central subfield thickness (µm).(Up to three months)
- Changes from baseline in retinal peripheral capillary free zone (mm²).(Up to three months)
- Changes from baseline in retinal foveal avascular zone (mm²).(Up to three months)
- Changes from baseline in retinal capillary density (%).(Up to three months)
- Changes from baseline in retinal non-perfusion zones (mm²).(Up to three months)
- Change in macular central subfield thickness.(Up to three months)
- Changes in retinal peripheral capillary free zone.(Up to three months)
- Changes in retinal foveal avascular zone.(Up to three months)
- Changes in retinal capillary density.(Up to three months)
- Changes in retinal non-perfusion zones.(Up to three months)
研究者
Maria Grant
Eivor and Alston Callahan, MD, Endowed Chair in Ophthalmology
University of Alabama at Birmingham