Pioglitazone for Chronic Kidney Disease

Recruiting at 1 trial location

Overseen By Paul J Fadel, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: The University of Texas at Arlington

Must not be taking: Dilantin, Oral contraceptives

Disqualifiers: Heart failure, Liver disease, Cancer, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 1 month

28 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether pioglitazone, a drug typically used for type 2 diabetes, can aid people with chronic kidney disease (CKD) by reducing nerve signals that increase heart risks. CKD patients often have an overactive nervous system, which can lead to heart problems. The study aims to determine if pioglitazone can calm these nerve impulses. Participants will receive either pioglitazone or a placebo (a pill with no active drug) for one month. Individuals with CKD at stages 3 or 4, experiencing kidney issues like decreased filtration, may be suitable for this trial. As a Phase 4 trial, this research seeks to understand how the already FDA-approved and effective treatment can benefit more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are using Dilantin or oral contraceptives due to potential drug interactions with the study drug, pioglitazone.

What is the safety track record for pioglitazone?

Research has shown that pioglitazone is generally safe for people with chronic kidney disease (CKD). Some studies have found that pioglitazone can safely aid individuals with type 2 diabetes and advanced CKD by reducing negative health outcomes, without an increase in serious side effects. Another study noted that pioglitazone was well tolerated, even in patients with varying levels of kidney function.

In this study, the dose is lower, which might further reduce side effects. This suggests that pioglitazone is a well-tolerated option for those considering participation in trials using this medication. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about pioglitazone for chronic kidney disease (CKD) because it offers a new approach by focusing on reducing ADMA (asymmetric dimethylarginine) and sympathetic nerve activity. While current treatments for CKD often center around blood pressure management and blood sugar control, pioglitazone is unique as it belongs to the thiazolidinedione class, primarily used for type 2 diabetes. This drug works by improving insulin sensitivity, which might also help alleviate CKD symptoms by targeting pathways not addressed by typical CKD medications. Its potential dual benefits for diabetes and CKD make it a promising candidate for improving patient outcomes.

What evidence suggests that pioglitazone might be an effective treatment for chronic kidney disease?

Research has shown that pioglitazone, a drug commonly used for diabetes, might also benefit people with chronic kidney disease (CKD). In previous studies, CKD patients who took pioglitazone experienced fewer heart problems, such as heart attacks and strokes. Another study found that pioglitazone reduced nerve activity related to heart issues in CKD patients. Additionally, pioglitazone proved safe and effective for CKD patients without causing serious side effects. This trial will compare pioglitazone to a placebo to assess its potential as a promising option for improving heart health in people with CKD. ^{2 6 7 8 9}

Who Is on the Research Team?

Paul J Fadel, PhD

Principal Investigator

University of Texas at Arlington

Are You a Good Fit for This Trial?

This trial is for men and women aged 35-70 with moderate to severe chronic kidney disease (stages 3 and 4). Participants should have a certain level of kidney function based on lab tests. People with heart failure, current smokers, those allergic to Glitazones, or with recent serious health issues like myocardial infarction or liver disease are not eligible.

Inclusion Criteria

My kidney function is moderately to severely reduced.

I am between 35 and 70 years old.

Exclusion Criteria

I have heart failure.

I have had kidney stones in the past.

I am not taking Dilantin or oral contraceptives due to their interaction with glitazones.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Pioglitazone or placebo for 1 month to assess reduction in ADMA and sympathetic nerve activity

1 month

1 visit (in-person) for drug dispensation and instructions

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person) for follow-up assessments

What Are the Treatments Tested in This Trial?

Interventions

• Pioglitazone
• Placebo

Trial Overview The study is testing if Pioglitazone, a diabetes drug, can lower overactive nerve signals in CKD patients which might reduce their cardiovascular risks. Patients will be randomly assigned to receive either Pioglitazone or a placebo for comparison.

How Is the Trial Designed?

Group I: Pioglitazone Active Control 1 Intervention

The subjects will be given 1 month supply of Pioglitazone pills. Pioglitazone is a class of anti-diabetic drugs called thiazolidinediones that are primarily used in the treatment of type 2 diabetes. The aim of the study is to determine if Pioglitazone also reduces ADMA and sympathetic nerve activity in CKD patients. This drug will be taken orally as a pill or capsule for one month. The dosage is 15 mg/day. This is on the lower dosage side for pioglitazone with the maximum dosage being 45mg/day. The research subjects are not responsible for the cost of the drug or for drug administration costs. The subjects will be verbally instructed to take 1 pill everyday by mouth, for 1 month. In addition, the pill bottle will be labeled with the same instructions.

Group II: Placebo Placebo Group 1 Intervention

Placebo pills are made of avicel microcrystalline cellulose and magnesium stearate, which are inactive ingredients in the Pioglitazone pills. The placebo pills will be of similar color and appearance as the Pioglitazone pills

Pioglitazone is already approved in United States for the following indications:

Approved in United States as Actos for:

• Type 2 diabetes mellitus

Who Is Running the Clinical Trial?

The University of Texas at Arlington

Lead Sponsor

Trials

48

Recruited

7,300+

University of Texas, Southwestern Medical Center at Dallas

Collaborator

Trials

18

Recruited

21,200+

Published Research Related to This Trial

In a study of 50 patients with diabetic nephropathy, those treated with beraprost sodium (BPS) showed a significant improvement in serum albumin levels and a slower decline in estimated glomerular filtration rate (eGFR) compared to those receiving conventional treatment alone.

After more than 12 months of treatment, the decline in eGFR was significantly less in the BPS group (-10.1 ml/min/1.73 m²) compared to the control group (-25.9 ml/min/1.73 m²), indicating that BPS may provide long-term reno-protective effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beraprost Sodium Delays the Decline of Glomerular Filtration Rate in Patients with Diabetic Nephropathy: A Retrospective Study. Zhou, J., Jiang, S., Li, Z., et al.[2023]

In a study involving 27 participants with varying degrees of renal function, pioglitazone was found to be well tolerated across all groups, indicating its safety in patients with renal impairment.

While patients with severe renal impairment showed increased serum concentrations of pioglitazone and its metabolites, the pharmacokinetic profiles were not significantly different from those with normal or moderate renal function, suggesting that dose adjustments may not be necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pharmacokinetics of pioglitazone in patients with impaired renal function. Budde, K., Neumayer, HH., Fritsche, L., et al.[2019]

In a study of 36 patients with type 2 diabetes on hemodialysis, adding pioglitazone to insulin therapy significantly reduced the daily insulin dose by 35% and improved HbA1c levels, indicating better glycemic control.

Pioglitazone was well-tolerated with no increased risk of hypoglycemia or volume overload, making it a safe adjunct treatment for patients with advanced kidney disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the Effects of Pioglitazone versus Placebo when Given in Addition to Standard Insulin Treatment in Patients with Type 2 Diabetes Mellitus Requiring Hemodialysis: Results from the PIOren Study. Galle, J., Kleophas, W., Dellanna, F., et al.[2022]

In a study of 75 patients with type 2 diabetes and chronic kidney disease, low dose pioglitazone (7.5 mg/day) provided similar glycemic control as standard dose pioglitazone (15 mg/day) over 24 weeks, with no significant difference in HbA1c levels.

The low dose pioglitazone resulted in less weight gain and fluid retention compared to the standard dose, making it a safer option for patients with CKD who are at risk for these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of low dose pioglitazone compared with standard dose pioglitazone in type 2 diabetes with chronic kidney disease: A randomized controlled trial. Satirapoj, B., Watanakijthavonkul, K., Supasyndh, O.[2022]

In a rat model of chronic kidney disease, pioglitazone significantly improved kidney structure and function, as shown by reduced levels of harmful substances like blood urea nitrogen and creatinine.

Pioglitazone enhanced the kidney's antioxidative capacity and inhibited harmful angiogenesis by down-regulating key angiogenic factors, suggesting it could be a promising treatment for chronic kidney diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pioglitazone, a Peroxisome Proliferator-Activated Receptor x03B3; Agonist, Ameliorates Chronic Kidney Disease by Enhancing Antioxidative Capacity and Attenuating Angiogenesis in the Kidney of a 5/6 Nephrectomized Rat Model. Sun, L., Yuan, Q., Xu, T., et al.[2019]

In a study of 798 patients with newly diagnosed type 2 diabetes, metformin was associated with a lower risk of developing chronic kidney disease (CKD) compared to sulfonylureas, which showed a trend towards increased risk of proteinuria.

The use of thiazolidinediones (THZs) did not significantly differ from metformin in terms of CKD risk, indicating that metformin may be a safer option for kidney health in diabetic patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative effectiveness research using electronic health records: impacts of oral antidiabetic drugs on the development of chronic kidney disease. Masica, AL., Ewen, E., Daoud, YA., et al.[2022]

Pioglitazone has been evaluated for safety in over 5,400 subjects, with more than 3,500 receiving the drug, resulting in over 2,500 patient-years of exposure, indicating a robust safety profile.

The trials demonstrated that pioglitazone is well-tolerated both as a standalone treatment and in combination with other diabetes medications, with comprehensive monitoring of adverse events and health metrics throughout the studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of pioglitazone. Hanefeld, M., Belcher, G.[2022]

Pioglitazone effectively increases insulin sensitivity and improves glycemic control in patients with type 2 diabetes, whether used alone or in combination with other medications, based on clinical trials.

The medication is generally well tolerated, with weight gain and edema being the most common side effects, and it also shows potential benefits in reducing cardiovascular risk and arteriosclerosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spotlight on pioglitazone in type 2 diabetes mellitus. Waugh, J., Keating, GM., Plosker, GL., et al.[2019]

In a study involving male Sprague Dawley rats with type-2 diabetes, treatment with pioglitazone for 8 weeks significantly reduced kidney weight and improved kidney health compared to untreated diabetic rats.

Pioglitazone also decreased the expression of hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF), which are associated with the progression of diabetic nephropathy, indicating its potential to mitigate kidney damage in diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of pioglitazone on diabetic nephropathy and expression of HIF-1α and VEGF in the renal tissues of type 2 diabetic rats. Xu, X., Chen, P., Zheng, Q., et al.[2018]

In a study involving 40 diabetic rats, pioglitazone significantly reduced kidney damage, as indicated by lower levels of blood urea nitrogen (BUN) and serum creatinine (SCr) compared to untreated diabetic rats.

The protective effect of pioglitazone on kidney injury was found to be dose-dependent, with higher doses leading to better preservation of kidney structure and function, likely through increased expression of the podocalyxin protein.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protective effect of pioglitazone on kidney injury in diabetic rats. Peng, XH., Liang, PY., Ou, SJ., et al.[2018]

Over 50% of U.S. adults with chronic kidney disease (CKD) are using potentially inappropriate medications (PIMs), with the highest prevalence (66.6%) found in CKD-unaware patients with stages 4-5 CKD, which can lead to adverse outcomes.

CKD awareness significantly affects the use of certain PIMs, such as NSAIDs and metformin, indicating that better awareness could help reduce the use of these medications in higher CKD stages and improve patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of Potentially Nephrotoxic Medications by U.S. Adults with Chronic Kidney Disease: NHANES, 2011-2016. Kurani, S., Jeffery, MM., Thorsteinsdottir, B., et al.[2021]

In a study involving adult male Wistar rats, pioglitazone significantly improved renal function and reduced arteriolopathy when administered alongside cyclosporine (CsA), suggesting its protective effects against CsA-induced nephrotoxicity.

Pioglitazone appears to work by downregulating the pro-fibrotic cytokine PAI-1 and increasing the regulatory protein Smad7, which may help mitigate chronic inflammation and fibrosis in the kidneys.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pioglitazone limits cyclosporine nephrotoxicity in rats. Pereira, MG., Câmara, NO., Campaholle, G., et al.[2022]

Citations

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Effect of Pioglitazone on Cardiovascular Outcome in Diabetes ... Patients who had CKD and were treated with pioglitazone were less likely to reach a composite end point of all-cause death, MI, and stroke, independent of the ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03471117

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Safety and efficacy of low dose pioglitazone compared with ... Available data among patients with CKD suggest that pioglitazone was effective and safe, with no increase in serious adverse effects. However, ...

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Glitazones in chronic kidney disease: Potential and concerns This systematic review examines the effects of glitazones on cardiovascular and renal outcomes in chronic kidney disease patients.

5. withpower.com withpower.com/trial/phase-4-kidney-diseases-3-2018-4aa51

Pioglitazone for Chronic Kidney Disease In a rat model of chronic kidney disease, pioglitazone significantly improved kidney structure and function, as shown by reduced levels of harmful substances ...

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Pioglitazone Reduces Mortality and Adverse Events in ... In conclusion, this study revealed that pioglitazone can safely reduce several adverse outcomes in T2D patients with advanced CKD.

7. amsad.termedia.pl amsad.termedia.pl/Pioglitazone-in-diabetic-kidney-disease-forgotten-but-not-gone,151046,0,2.html

Pioglitazone in diabetic kidney disease: forgotten but not gone Pioglitazone reduces mortality and adverse events in patients with type 2 diabetes and with advanced chronic kidney disease: National Cohort ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S014929182400198X

Efficacy and Safety of Pioglitazone Add-on in Patients with ... The purpose of this study was to determine the efficacy and safety profile of pioglitazone compared with placebo (PBO) in patients with type 2 diabetes (T2D)

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC1884238/

The pharmacokinetics of pioglitazone in patients with ... Pioglitazone was well tolerated in patients with varying degrees of renal impairment. Although mean serum concentrations of pioglitazone and its metabolites ...