Clinical Trial Details
— Status: Completed
Administrative data
NCT number |
NCT03636152 |
Other study ID # |
CARB-013-17F |
Secondary ID |
ICX001661A |
Status |
Completed |
Phase |
Phase 2
|
First received |
|
Last updated |
|
Start date |
December 14, 2018 |
Est. completion date |
January 31, 2024 |
Study information
Verified date |
February 2024 |
Source |
VA Office of Research and Development |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
Cardiovascular disease (CVD) is the largest concerns for patients with Chronic kidney disease
(CKD). At present time the investigators do not have proven effective strategies to reduce
high CVD related deaths in CKD. This study assesses a novel therapy (hydroxychloroquine, HCQ)
for the treatment of CVD in patients with CKD. This is the first human proof-of-concept study
and is planned to be conducted among US Veterans, who suffer from both CKD and CVD at a
disproportionately greater rates. The outcome of this study has the potential to provide an
entirely new line of therapy for the treatment of CVD in CKD.
Description:
Cardiovascular disease (CVD) is the most prominent cause of morbidity and mortality among
patients with chronic kidney disease (CKD), and end stage kidney disease (ESKD).
Unfortunately at the present time, the investigators do not have an effective treatment to
reduce the high CVD mortality in these populations. Accelerated atherosclerosis,
inflammation, and vascular stiffness are prominent factors contributing to CVD in CKD.
Interventions that can effectively counter these factors may provide significant benefits for
the management of CVD in CKD. Hydroxychloroquine (HCQ) is an inexpensive and safe
anti-inflammatory drug that has been in clinical use for over 4 decades even in patients with
CKD and ESKD. In recent times, multiple in vitro, in vivo, and human cohort based data have
shown that HCQ benefits multiple parameters of CVD, including inflammation, endothelial
function, metabolic syndrome, insulin sensitivity and atherosclerosis. Recently the
investigators through the animal studies validated that HCQ indeed has significant
anti-atherosclerosis and vasculoprotective effects in CKD milieu. The investigators further
conducted a small, human, feasibility study that shows a potential for HCQ on parameters
relevant to CVD in CKD. As the next step, the investigators propose to conduct a
proof-of-concept, randomized controlled trial (RCT) to ascertain the effects of HCQ on the
structural, functional, and biochemical measures of atherosclerosis and CVD. The
investigators will enroll 100 albuminuric, stage 3b CKD subjects in a with 1:1 allocation
(HCQ : placebo) and treat for a duration of 18 months. The investigators' three specific aims
are as follows: Specific Aim (SA) 1 will evaluate the ability of HCQ, compared to placebo, to
slow the progression, or reverse atherosclerosis through serial examination of carotid
atherosclerosis through non-contrast MRI performed at baseline and after 9 and 18 months of
treatment with HCQ or placebo. The investigators will measure the change in total carotid
plaque volume (TPV) as the primary outcome measure, and changes in total plaque surface area,
maximal stenosis, and the type (fibrous, stable, or unstable), and stability of plaques as
secondary outcome measures. SA2 will evaluate the impact of HCQ vs. placebo on inflammation
(SA2a), and vascular stiffness (SA2b) at baseline, and at 6, 9, 12, and 18 months as
secondary outcome measures. The investigators will quantify inflammation through
high-sensitivity C-reactive protein (SA2a) and vascular stiffness through measurements of
aortic pulse wave velocity (SA2b). Specific Aim 3 will examine the effect of HCQ and placebo
on the trends of hard cardiac and renal outcomes and drug safety. The results of this trial
will provide critical preliminary data to justify and plan a definitive, multicenter RCT to
examine the effects of HCQ on hard outcomes of CVD in CKD. Additionally, this study may
provide insights into the importance of select inflammatory and vascular factors in CVD with
wider future implications for those with CKD and perhaps the general population.