Liver X Receptor (LXR) as a Novel Therapeutic Target in Diabetic Retinopathy (DR)

NCT ID: NCT03403686

Last Updated: 2025-09-17

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 104 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2018-01-11
• Study Completion Date: 2026-12-31

Brief Summary

Results from large clinical trials demonstrate a strong association between lipid abnormalities and progression of the most common microvascular complication, diabetic retinopathy (DR). We found that activation of a master regulator of cholesterol metabolism, the nuclear hormone receptors liver X receptors (LXRα/LXRβ), prevents DR in rodent models. In this application, we seek to understand the mechanisms responsible for the beneficial effects of LXR agonists on retina and on bone marrow (BM) to preserve the function of reparative cells while reducing inflammatory cell.

Detailed Description

Diabetic retinopathy (DR) is a disabling microvascular complication. Despite recent advances using pharmacotherapy, a cure for DR has yet to be realized. Thus, a conceptual and technical breakthrough to identify novel targets, and a strategy to cure this complication is paramount. We believe that the recent clinical evidence from large clinical trials demonstrating a strong association between lipid abnormalities and DR progression and the discovery that activation of the nuclear hormone receptors liver X receptors (LXRα/LXRβ) prevents DR in rodent models offers such a breakthrough. The detrimental effect of dyslipidemia is not limited to the vasculature but also leads to dysfunction of circulating angiogenic cells (CAC) and of macrophages. The endogenous ligands for LXRs are oxidative metabolites of cholesterol that serve as intracellular cholesterol "sensors". LXR agonists operate, in part, by transcriptional upregulation of genes involved in promoting cholesterol efflux and inhibition of cholesterol uptake; and by inhibiting inflammation. Our published studies and new preliminary data show that pharmacological LXR activation prevents DR development in both T1D and T2D rodent models. In this application, we seek to understand the mechanisms involved in this beneficial effect. We put forth the hypothesis that LXR activation will restore cholesterol homeostasis in the diabetic retina and correct diabetes-induced bone marrow dysfunction to sustain CAC levels and function and to reduce of myeloid cell production.

Conditions

Diabetic Retinopathy

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: OTHER

Study Groups

Controls

Any man or woman between the ages of 21- 98 years of age will be eligible to participate. To participate in the study as a study subject we will require that the subject must carry the diagnosis of healthy control.

blood draw

Intervention Type: BIOLOGICAL

Blood sample will be obtained and CD34+ cells will be isolated for functional testing.

Diabetic no retinopathy

Patients with diabetes but with no evidence of diabetic retinopathy

blood draw

Intervention Type: BIOLOGICAL

Blood sample will be obtained and CD34+ cells will be isolated for functional testing.

Diabetic with mild retinopathy

Diabetics with mild non proliferative diabetic retinopathy (NPDR).

blood draw

Intervention Type: BIOLOGICAL

Blood sample will be obtained and CD34+ cells will be isolated for functional testing.

Diabetic with moderate retinopathy

Diabetics with moderate NPDR

blood draw

Intervention Type: BIOLOGICAL

Blood sample will be obtained and CD34+ cells will be isolated for functional testing.

Diabetics with severe retinopathy

Diabetic with severe NPDR.

blood draw

Intervention Type: BIOLOGICAL

Blood sample will be obtained and CD34+ cells will be isolated for functional testing.

Diabetics with proliferative diabetic retinopathy (PDR)

Diabetics with proliferative diabetic retinopathy (PDR)

blood draw

Intervention Type: BIOLOGICAL

Blood sample will be obtained and CD34+ cells will be isolated for functional testing.

Interventions

blood draw

Blood sample will be obtained and CD34+ cells will be isolated for functional testing.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Any man or woman between the ages of 21- 98 years of age will be eligible to participate. To participate in the study as a study subject we will require: a) the subject must either carry the diagnosis of diabetes or be a healthy aged control and b) the patient be willing and have the ability to cooperate with the protocol.

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 98 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Alabama at Birmingham

OTHER

Sponsor Role: lead

Responsible Party

Maria Grant

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Maria B Grant, MD

Role: PRINCIPAL_INVESTIGATOR

University of Alabama at Birmingham

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Jennifer Moorer

Role: CONTACT

jmoorer@uabmc.edu

205 325 8674

Facility Contacts

Jennifer Moorer

Role: primary

jmoorer@uabmc.edu

2053258674

Other Identifiers

300000068

Identifier Type: -

Identifier Source: org_study_id