Clinical Trial Details
— Status: Enrolling by invitation
Administrative data
| NCT number |
NCT05132660 |
| Other study ID # |
C3825-R |
| Secondary ID |
|
| Status |
Enrolling by invitation |
| Phase |
Early Phase 1
|
| First received |
|
| Last updated |
|
| Start date |
July 1, 2022 |
| Est. completion date |
December 31, 2028 |
Study information
| Verified date |
May 2024 |
| Source |
VA Office of Research and Development |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
To determine if levodopa will slow the appearance of blood vessel changes in the eyes of
patients with diabetes. Treatment will be started in patients with diabetes show delays in
the electrical activity of the retina when measured non-invasively with a electroretinogram.
Description:
Diabetic Retinopathy (DR) is a leading cause of vision loss in the US. To detect DR,
individuals with diabetes are instructed to receive annual eye exams until visible
retinopathy such as hemorrhages or aneurysms appear that often take years to develop. Even
so, treatment is only provided when visually threatening disease is detected. The
investigators' group and others have established that in people with diabetes, retinal
neuronal dysfunction precedes clinically visible retinopathy. Non-invasive recordings of
retinal function using the electroretinogram (ERG) have shown dysfunction with diabetes,
particularly in the oscillatory potentials (OPs) that are generated by inner retinal neurons.
A fundamental gap in the knowledge of DR pathology is whether neuronal dysfunction is
associated with or causal to the late stage vascular defects. The overall hypothesis is that
neuronal defects precede vascular defects in DR and that treating neuronal deficits early in
DR will prevent late stage vascular defects that result in vision loss.
Dopamine, a key neuromodulator in the retina, is reduced in DR. The investigators
demonstrated that treating rodent models of diabetes with levodopa, a dopamine precursor, is
neuroprotective for neuronal dysfunction. Importantly, the investigators also showed that in
patients with diabetes and retinal dysfunction, but without retinopathy, levodopa taken for
only 2 weeks restored retinal dysfunction to normal levels. Thus, the preliminary data
suggest that earlier screening and treatment are possible to prevent or delay retinal
dysfunction in early DR. Since current clinical management of DR is directed at more advanced
stages of disease when vascular defects are present, it is critical to determine if levodopa
will also prevent vascular pathology.
The investigators propose the following specific aims to investigate the link between
neuronal and vascular defects in DR by using neuronal (dim flash ERG) and vascular (fundus
photography and optical coherence tomography angiography) primary outcome measures:
Aim 1: Investigate whether the appearance of early neuronal dysfunction predicts late stage
vascular pathology in diabetes. The investigators propose follow-up testing on a cohort of
participants with diabetes, and normal or delayed OPs, from a prior clinical study to
determine how many develop signs of retinal vascular defects after 3-5 years.
Aim 2: Determine whether levodopa treatment initiated at detection of retinal dysfunction
will prevent retinal dysfunction and vascular defects. The investigators will conduct a
randomized clinical trial with levodopa versus placebo using participants with diabetes and
confirmed OP delays from two groups: 1) without retinopathy and 2) with the earliest signs of
DR (microaneurysms). Patients will receive levodopa or placebo twice daily for 6- or
24-months. For the 6-month duration, testing will be done at baseline, 3 months and 6 months.
Patients will then return to routine standard of care and be re-tested at 12 and 24 months.
For the 24-month duration, testing will be done at baseline and every 3 months until 24
months. Participants will be carefully monitored for levodopa side effects with the
assistance of a neurologist.
Determining the association between neuronal and vascular defects in DR is critical to
shifting clinical practice toward early diagnostic markers, a move that could transform the
way DR is monitored and treated, ultimately leading to better preservation of normal visual
function.
