Integrative Liver-Targeted Therapy for Diabetic Macular Edema: Using "Tauroursodeoxycholate" or Traditional Chinese Medicine.

Official title

Integrative Liver-Targeted Therapy for Diabetic Macular Edema: Combining Tauroursodeoxycholate and Traditional Chinese Medicine.

Overview

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.

Interventions

• Dietary supplement Tauroursodeoxycholate (TUDCA)
  TUDCA is a hydrophilic taurine-conjugated form of Ursodeoxycholic acid (UDCA).
• Dietary supplement Traditional Chinese Medicine (mQJDHW)
  The components of this formula are 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.
• Drug placebo capsule
  The placebo has no active ingredient.

Primary outcome measures

• Change from baseline in macrophage-like cell density (cells/mm²). [Time frame: Up to three months]
• Change from baseline in best-corrected visual acuity (ETDRS letters). [Time frame: Up to three months]
• Change from baseline in serum neuroinflammatory makers. [Time frame: Up to three months]
• Change from baseline in serum hepatic biomarkers. [Time frame: Up to three months]

Secondary outcome measures (5)

• Change from baseline in macular central subfield thickness (µm). [Time frame: Up to three months]
• Changes from baseline in retinal peripheral capillary free zone (mm²). [Time frame: Up to three months]
• Changes from baseline in retinal foveal avascular zone (mm²). [Time frame: Up to three months]
• Changes from baseline in retinal capillary density (%). [Time frame: Up to three months]
• Changes from baseline in retinal non-perfusion zones (mm²). [Time frame: Up to three months]

Eligibility criteria

Inclusion criteria

• 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 20/200.
• 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.

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 1 center

• University of Alabama at Birmingham — Birmingham

Identifiers

NCT: NCT07457632 · IRB-300016314 · UAB Dept. of Ophthalmology

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗