Volenrelaxin for Chronic Kidney Disease
Recruiting in Palo Alto (17 mi)
+35 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Waitlist Available
Sponsor: Eli Lilly and Company
Prior Safety Data
Trial Summary
What is the purpose of this trial?The main purpose of this study is to investigate the efficacy and safety of Volenrelaxin in adults with Chronic Kidney Disease. The study will last about 24 weeks.
Do I need to stop my current medications to join the trial?
You can continue your current medications if they are stable. You must stay on your ACE inhibitor or ARB and any other CKD or diabetes medications you are already taking.
What data supports the idea that Volenrelaxin for Chronic Kidney Disease is an effective drug?
The available research does not provide specific data on the effectiveness of Volenrelaxin for Chronic Kidney Disease. Instead, it highlights other treatments like renin-angiotensin system inhibitors, sodium-glucose cotransporter-2 inhibitors, and glucagon-like peptide-1 receptor agonists as effective options. These treatments have shown significant benefits in managing kidney disease, such as reducing the risk of kidney damage and slowing disease progression. Without specific data on Volenrelaxin, it's unclear how it compares to these established treatments.
12345What safety data exists for Volenrelaxin (LY3540378) in treating chronic kidney disease?
The provided research does not contain specific safety data for Volenrelaxin (LY3540378) in the treatment of chronic kidney disease. The articles focus on other treatments such as SGLT2 inhibitors, mineralocorticoid receptor antagonists like finerenone, and their safety profiles. Further research or clinical trial data specific to Volenrelaxin would be needed to answer this question.
13678Eligibility Criteria
This trial is for adults with Chronic Kidney Disease. Specific eligibility details are not provided, but typically participants should meet certain health criteria and may be excluded based on factors that could impact the study's results or their own safety.Inclusion Criteria
I have been on a stable diabetes treatment for over 3 months.
I have been taking the highest dose I can tolerate of an ACE inhibitor or ARB for the last 90 days.
I have been diagnosed with Chronic Kidney Disease according to KDIGO criteria.
+1 more
Exclusion Criteria
I have been on dialysis in the last 90 days.
Have HbA1c >8.5% at screening
I have had a heart attack, stroke, or other major heart issues in the last 3 months.
+8 more
Participant Groups
The trial is testing Volenrelaxin's effectiveness and safety over a 12-week period against a placebo to see if it can help adults with Chronic Kidney Disease.
4Treatment groups
Experimental Treatment
Placebo Group
Group I: Volenrelaxin Dose 3Experimental Treatment1 Intervention
Participants will receive Volenrelaxin SC
Group II: Volenrelaxin Dose 2Experimental Treatment1 Intervention
Participants will receive Volenrelaxin SC
Group III: Volenrelaxin Dose 1Experimental Treatment1 Intervention
Participants will receive Volenrelaxin subcutaneously (SC)
Group IV: PlaceboPlacebo Group1 Intervention
Participants will receive Placebo SC
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Elite Clinical Research CenterFlint, MI
Lucas Research, Inc.Morehead City, NC
Eastern Nephrology Associates- New Bern Office Loc. 1New Bern, NC
Rancho Research InstituteDowney, CA
More Trial Locations
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Who Is Running the Clinical Trial?
Eli Lilly and CompanyLead Sponsor
References
A Narrative Review of Diabetic Kidney Disease: Previous and Current Evidence-Based Therapeutic Approaches. [2022]Diabetic kidney disease (DKD) is one of the most important diabetic complications. DKD is also the most common cause of chronic kidney disease (CKD) and end-stage renal disease. This review focused on potential therapeutic drugs for which there is established evidence of treatment for DKD. The earliest evidence for DKD treatment was established with renin-angiotensin system (RAS) inhibitors; however, their efficacy was partial. Recently, the sodium-glucose co-transporter 2 (SGLT2) inhibitors, including empagliflozin (EMPA-REG Outcome), canagliflozin (CREDENCE trial), and dapagliflozin (DAPA-CKD), demonstrated a significant and clinically relevant reduction in the risks of albuminuria and progression of nephropathy, doubling of serum creatinine levels, and initiation of renal replacement therapy. Additionally, incretin-based therapeutic agents, such as glucagon-like peptide 1, liraglutide (LEADER), and dipeptidyl peptidase 4 inhibitors, linagliptin (CARMERINA) have elicited vasotropic actions, suggesting a potential for reducing the risk of DKD. Until recently, mineralocorticoid receptor antagonists (MRAs) have not been suitable for DKD treatment because of their adverse effect of hyperkalemia. In contrast, finerenone, a non-steroidal MRA, significantly reduced renal composite endpoint without severe hyperkalemia that would force its discontinuation (FIDELIO-DKD). Thus, the mainstay treatments of DKD are RAS inhibitors, SGLT2 inhibitors, incretin-based therapeutic agents, and non-steroidal MRA, or in other words, the DKD "fantastic four".
Candidate composite biomarker to inform drug treatments for diabetic kidney disease. [2023]Current guidelines recommend renin angiotensin system inhibitors (RASi) as key components of treatment of diabetic kidney disease (DKD). Additional options include sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucagon-like peptide 1 receptor agonists (GLP1a), and mineralocorticoid receptor antagonists (MCRa). The identification of the optimum drug combination for an individual is difficult because of the inter-, and longitudinal intra-individual heterogeneity of response to therapy.
The emerging pillars of chronic kidney disease: no longer a bystander in metabolic medicine. [2023]Chronic kidney disease (CKD) represents an enormous healthcare burden, the management of which has been stagnant for the last couple of decades, with blockade of the renin-angiotensin-aldosterone system (RAAS) the most potent tool available to retard kidney disease progression. In the new cardiometabolic era, sodium-glucose cotransporter-2 inhibitors (SGLT2i) have emerged as forerunners in addressing combined cardiorenal risk. This review summarises the evidence for SGLT2i use in diabetic and non-diabetic CKD and examines the risk:benefit profile in this population. Novel non-steroidal mineralocorticoid receptor antagonists are also considered as an emerging pillar of CKD management, and their role in optimising the cardiorenal health of patients with diabetic kidney disease is discussed.
Apararenone in patients with diabetic nephropathy: results of a randomized, double-blind, placebo-controlled phase 2 dose-response study and open-label extension study. [2021]We investigated the efficacy and safety of apararenone (MT-3995), a non-steroidal compound with mineralocorticoid receptor agonist activity, in patients with stage 2 diabetic nephropathy (DN).
Management of type 2 diabetes in chronic kidney disease. [2021]The management of patients with type 2 diabetes and chronic kidney disease (CKD) encompasses lifestyle modifications, glycemic control with individualized HbA1c targets, and cardiovascular disease risk reduction. Metformin and sodium-glucose cotransporter-2 inhibitors are first-line agents. Glucagon-like peptide-1 receptor agonists are second-line agents. The use of other antidiabetic agents should consider patient preferences, comorbidities, drug costs, and the risk of hypoglycemia. Renin-angiotensin-aldosterone system inhibitors are strongly recommended for patients with diabetes, hypertension, and albuminuria. Non-steroidal mineralocorticoid receptor antagonists, which pose less risk of hyperkalemia than steroidal agents, are undergoing further evaluation among patients with diabetic kidney disease. Here, we discuss important advancements in the management of patients with type 2 diabetes and CKD.
Finerenone: A Novel Third-Generation Mineralocorticoid Receptor Antagonist. [2023]Finerenone is a novel third-generation, selective nonsteroidal mineralocorticoid receptor antagonist (MRA) that was approved by the Food and Drug Administration in July of 2021 for its use in adults with chronic kidney disease and Type II diabetes mellitus. Randomized controlled trials The Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease and Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease showed decreased adverse kidney and cardiovascular outcomes, respectively, in this population. The incidence of hyperkalemia, while higher in the study versus placebo group, was lower than older generations of MRAs (spironolactone and eplerenone) and proved to be an infrequent cause for drug discontinuation. The incidences of other adverse effects such as gynecomastia and acute kidney injury were similar in both the study and the placebo groups. This is the first third-generation MRA authorized to use to reduce the burden of cardiorenal disease.
Mineralcorticoid receptor blockers in chronic kidney disease. [2022]There are many experimental data supporting the involvement of aldosterone and mineralcorticoid receptor (MR) activation in the genesis and progression of chronic kidney disease (CKD) and cardiovascular damage. Many studies have shown that in diabetic and non-diabetic CKD, blocking the renin-angiotensin-aldosterone (RAAS) system with conversion enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARBs) decreases proteinuria, progression of CKD and mortality, but there is still a significant residual risk of developing these events. In subjects treated with ACEi or ARBs there may be an aldosterone breakthrough whose prevalence in subjects with CKD can reach 50%. Several studies have shown that in CKD, the aldosterone antagonists (spironolactone, eplerenone) added to ACEi or ARBs, reduce proteinuria, but increase the risk of hyperkalemia. Other studies in subjects treated with dialysis suggest a possible beneficial effect of antialdosteronic drugs on CV events and mortality. Newer potassium binders drugs can prevent/decrease hyperkalemia induced by RAAS blockade, and may reduce the high discontinuation rates or dose reduction of RAAS-blockers. The nonsteroidal MR blockers, with more potency and selectivity than the classic ones, reduce proteinuria and have a lower risk of hyperkalemia. Several clinical trials, currently underway, will determine the effect of classic MR blockers on CV events and mortality in subjects with stage 3b CKD and in dialysis patients, and whether in patients with type 2 diabetes mellitus and CKD, optimally treated and with high risk of CV and kidney events, the addition of finerenone to their treatment produces cardiorenal benefits. Large randomized trials have shown that sodium glucose type 2 cotransporter inhibitors (SGLT2i) reduce mortality and the development and progression of diabetic and nondiabetic CKD. There are pathophysiological arguments, which raise the possibility that the triple combination ACEi or ARBs, SGLT2i and aldosterone antagonist provide additional renal and cardiovascular protection.
[Mineralcorticoid receptor blockers in chronic kidney disease]. [2022]There are many experimental data supporting the involvement of aldosterone and mineralcorticoid receptor (MR) activation in the genesis and progression of chronic kidney disease (CKD) and cardiovascular damage. Many studies have shown that in diabetic and non-diabetic CKD, blocking the renin- angiotensin-aldosterone (RAAS) system with conversion enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARBs) decreases proteinuria, progression of CKD and mortality, but there is still a significant residual risk of developing these events. In subjects treated with ACEi or ARBs there may be an aldosterone breakthrough whose prevalence in subjects with CKD can reach 50%. Several studies have shown that in CKD, the aldosterone antagonists (spironolactone, eplerenone) added to ACEi or ARBs, reduce proteinuria, but increase the risk of hyperkalemia. Other studies in subjects treated with dialysis suggest a possible beneficial effect of antialdosteronic drugs on CV events and mortality. Newer potassium binders drugs can prevent / decrease hyperkalemia induced by RAAS blockade, and may reduce the high discontinuation rates or dose reduction of RAAS-blockers. The nonsteroidal MR blockers, with more potency and selectivity than the classic ones, reduce proteinuria and have a lower risk of hyperkalemia. Several clinical trials, currently underway, will determine the effect of classic MR blockers on CV events and mortality in subjects with stage 3b CKD and in dialysis patients, and whether in patients with type 2 diabetes mellitus and CKD, optimally treated and with high risk of CV and kidney events, the addition of finerenone to their treatment produces cardiorenal benefits. Large randomized trials have shown that sodium glucose type 2 cotransporter inhibitors (SGLT2i) reduce mortality and the development and progression of diabetic and nondiabetic CKD. There are pathophysiological arguments, which raise the possibility that the triple combination ACEi or ARBs, SGLT2i and aldosterone antagonist provide additional renal and cardiovascular protection.
Dual blockade of the renin-angiotensin system in diabetic nephropathy: a randomized double-blind crossover study. [2019]Many patients with diabetic nephropathy (DN) have levels of albuminuria > 1 g/day and blood pressure >135/85 mmHg, despite antihypertensive combination therapy, including recommended doses of ACE inhibitors, e.g., lisinopril/enalapril at 20 mg daily. We tested the concept that such patients might benefit from dual blockade of the renin-angiotensin system (RAS).
Aliskiren combined with losartan in type 2 diabetes and nephropathy. [2022]Diabetic nephropathy is the leading cause of end-stage renal disease in developed countries. We evaluated the renoprotective effects of dual blockade of the renin-angiotensin-aldosterone system by adding treatment with aliskiren, an oral direct renin inhibitor, to treatment with the maximal recommended dose of losartan (100 mg daily) and optimal antihypertensive therapy in patients who had hypertension and type 2 diabetes with nephropathy.
Effects of Vitamin D Receptor Activation and Dietary Sodium Restriction on Residual Albuminuria in CKD: The ViRTUE-CKD Trial. [2018]Reduction of residual albuminuria during single-agent renin-angiotensin-aldosterone blockade is accompanied by improved cardiorenal outcomes in CKD. We studied the individual and combined effects of the vitamin D receptor activator paricalcitol (PARI) and dietary sodium restriction on residual albuminuria in CKD. In a multicenter, randomized, placebo (PLAC)-controlled, crossover trial, 45 patients with nondiabetic CKD stages 1-3 and albuminuria >300 mg/24 h despite ramipril at 10 mg/d and BP<140/90 mmHg were treated for four 8-week periods with PARI (2 μg/d) or PLAC, each combined with a low-sodium (LS) or regular sodium (RS) diet. We analyzed the treatment effect by linear mixed effect models for repeated measurements. In the intention-to-treat analysis, albuminuria (geometric mean) was 1060 (95% confidence interval, 778 to 1443) mg/24 h during RS + PLAC and 990 (95% confidence interval, 755 to 1299) mg/24 h during RS + PARI (P=0.20 versus RS + PLAC). LS + PLAC reduced albuminuria to 717 (95% confidence interval, 512 to 1005) mg/24 h (P<0.001 versus RS + PLAC), and LS + PARI reduced albuminuria to 683 (95% confidence interval, 502 to 929) mg/24 h (P<0.001 versus RS + PLAC). The reduction by PARI beyond the effect of LS was nonsignificant (P=0.60). In the per-protocol analysis restricted to participants with ≥95% compliance with study medication, PARI did provide further albuminuria reduction (P=0.04 LS + PARI versus LS + PLAC). Dietary adherence was good as reflected by urinary excretion of 174±64 mmol Na+ per day in the combined RS groups and 108±61 mmol Na+ per day in the LS groups (P<0.001). In conclusion, moderate dietary sodium restriction substantially reduced residual albuminuria during fixed dose angiotensin-converting enzyme inhibition. The additional effect of PARI was small and nonsignificant.