Pentoxifylline for Diabetic Kidney Disease

(PTXRx Trial)

Recruiting at 35 trial locations

Overseen By Cheryl C Odle, MBA

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: VA Office of Research and Development

Must not be taking: Pentoxifylline, Ketorolac, Riociguat

Disqualifiers: Type 1 diabetes, Organ transplant, others

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

Compensation: Varies

Number of Visits: 2

Duration: 5 years

2510 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether pentoxifylline, originally used for leg blood vessel issues, can protect kidneys from damage in people with diabetic kidney disease. Participants will receive either pentoxifylline or a placebo to determine if the medication can slow kidney disease progression and reduce the risk of death. This study suits U.S. Veterans with type 2 diabetes who receive care at a VA hospital and have diabetes-related kidney function issues. As a Phase 4 trial, this research aims to understand how this 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 currently using oral pentoxifylline, systemic ketorolac, or riociguat.

What is the safety track record for Pentoxifylline?

Research shows that pentoxifylline (PTX) is generally safe for use. Studies have found that PTX can reduce protein levels in urine, benefiting those with diabetic kidney disease. In one study, protein levels in urine dropped by about 19.6% after three months of PTX treatment.

Other research indicates that PTX can slow the decline of kidney function. For those taking PTX, kidney function decreased by only 2.1 units, compared to a 6.5 unit decrease in those not taking it. This suggests PTX might help protect the kidneys over time.

PTX has been used since 1984 for another condition, providing some confidence in its safety. However, like all medications, it can have side effects. Common ones include dizziness and nausea, but these are usually mild.

Overall, PTX appears safe, with research supporting its use for kidney-related issues. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike standard treatments for diabetic kidney disease, which often focus on controlling blood sugar and blood pressure, Pentoxifylline offers a novel approach by targeting inflammation and improving blood flow. This drug is unique because it works by increasing the flexibility of red blood cells, which enhances circulation and oxygen delivery to the kidneys. Researchers are excited about Pentoxifylline because it has the potential to slow the progression of kidney damage more effectively than existing options, offering hope for better management of this serious condition.

What is the effectiveness track record for Pentoxifylline in treating diabetic kidney disease?

Research has shown that pentoxifylline, which participants in this trial may receive, can aid individuals with diabetic kidney disease. Studies indicate that it reduces protein in the urine, a sign of kidney damage, and lowers certain blood substances that indicate kidney stress. Although it does not enhance the kidneys' overall filtering ability, it has been shown to slow the loss of kidney function. These findings suggest that pentoxifylline could help protect the kidneys from further damage in people with diabetes. Participants in this trial may also receive a placebo as part of the study's control arm. ^{1 2 3 5 6}

Who Is on the Research Team?

David J Leehey

Principal Investigator

Edward Hines Jr. VA Hospital, Hines, IL

Are You a Good Fit for This Trial?

This trial is for U.S. Veterans with Type 2 diabetes and diabetic kidney disease receiving care at a VA hospital. They must have specific levels of kidney function (eGFR) and urine albumin to creatinine ratio (UACR). Excluded are those allergic to PTX, on dialysis, with substance abuse issues, homeless, pregnant or not using contraception, recent cerebral hemorrhage sufferers, organ transplant recipients, unable to consent or expected to live less than a year.

Inclusion Criteria

You must be a veteran receiving care at a VA hospital with a local study team.

I have type 2 diabetes.

My kidney function falls into one of the specified groups based on my eGFR and UACR levels.

Exclusion Criteria

I have had kidney disease not caused by diabetes.

I am currently on dialysis.

I am currently taking oral pentoxifylline.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Ramp-up

Ramp-up phase to optimize procedures and assess recruitment rate

1 year

Multiple visits (in-person and virtual)

Treatment

Participants receive PTX or placebo with routine clinical care

5 years

2 visits (in-person), quarterly contacts (virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Pentoxifylline
• Placebo

Trial Overview The study tests if Pentoxifylline (PTX), a drug used since 1984 for leg blood vessel diseases can protect kidneys in diabetic patients. Participants will either receive PTX or a placebo in this nationwide study across 40 VA hospitals to see if it prevents worsening of kidney disease and delays death.

How Is the Trial Designed?

Group I: PTX Experimental Treatment 1 Intervention

Active drug

Group II: Placebo Placebo Group 1 Intervention

Placebo

Pentoxifylline is already approved in United States, Canada, European Union for the following indications:

Approved in United States as Trental for:

• Intermittent claudication

Approved in Canada as Trental for:

• Intermittent claudication

Approved in European Union as Trental for:

• Intermittent claudication

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Published Research Related to This Trial

Pentoxifylline (PTF) significantly reduces proteinuria and albuminuria in patients with type 2 diabetic nephropathy when used alongside ACE inhibitors or ARBs, indicating its potential as an effective treatment option.

While PTF is generally safe, with mild gastrointestinal symptoms being the most common side effects, further large-scale studies are needed to confirm its long-term renoprotective effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of combining pentoxifylline with angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker in diabetic nephropathy: a meta-analysis. Tian, ML., Shen, Y., Sun, ZL., et al.[2022]

In a study of 21 insulin-dependent diabetic patients with overt nephropathy, treatment with pentoxifylline significantly reduced urinary protein excretion and improved blood flow, indicating its potential effectiveness in managing kidney function.

Pentoxifylline therapy led to lower blood pressure and increased creatinine clearance over a 1-year follow-up, showing comparable results to conventional antihypertensive treatments, suggesting it could be a beneficial option for advanced nephropathy in diabetic patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pentoxifylline, total urinary protein excretion rate and arterial blood pressure in long-term insulin-dependent diabetic patients with overt nephropathy. Solerte, SB., Fioravanti, M., Patti, AL., et al.[2019]

Pentoxifylline significantly reduced proteinuria in patients with diabetic kidney disease, showing a decrease of 278 mg/d compared to placebo, based on a systematic review of 10 studies with 476 participants over a median duration of 6 months.

The efficacy of pentoxifylline in reducing proteinuria was comparable to that of captopril, indicating it may be a viable alternative treatment, especially for patients with overt proteinuria (over 300 mg/d).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of pentoxifylline on proteinuria in diabetic kidney disease: a meta-analysis. McCormick, BB., Sydor, A., Akbari, A., et al.[2018]

Pentoxifylline (PTX) was found to effectively reduce proteinuria in patients with chronic kidney disease (CKD), especially in those with type-1 diabetes and early renal impairment, based on a systematic review of 26 studies involving 1518 subjects.

While PTX showed some potential for improving renal function in advanced CKD stages, there is currently no conclusive evidence that it improves hard renal outcomes like doubling of serum creatinine or the need for dialysis, highlighting the need for further research on its long-term effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of pentoxifylline on renal outcomes in chronic kidney disease patients: A systematic review and meta-analysis. Leporini, C., Pisano, A., Russo, E., et al.[2018]

In a study involving 40 type 2 diabetic patients, adding pentoxifylline to standard treatment did not significantly reduce microalbuminuria compared to a placebo over a 6-month period.

While both groups showed a trend of decreased albumin to creatinine ratio and improved kidney function, the differences were not statistically significant, indicating that pentoxifylline may not provide additional benefits in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of pentoxifylline on microalbuminuria in diabetic patients: a randomized controlled trial. Shahidi, S., Hoseinbalam, M., Iraj, B., et al.[2020]

In a long-term trial involving 70 diabetic patients, oral pentoxifylline (1200 mg/day) significantly improved blood flow properties by enhancing erythrocyte filtrability and reducing fibrinogen levels over 24 months.

The treatment not only normalized blood rheology but also led to a notable decrease in proteinuria and albumin excretion, indicating that pentoxifylline is effective in managing diabetic vascular complications and may help slow disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diabetic retinal vascular complications and erythrocyte filtrability; results of a 2-year follow-up study with pentoxifylline. Solerte, SB., Ferrari, E.[2022]

Pentoxifylline (Trental) is proposed as an ideal adjunct therapy for chronic proliferative glomerulonephritides due to its beneficial characteristics.

Theoretical evidence suggests that pentoxifylline may also help protect against and reduce tubulo-interstitial fibrosis in affected kidneys, potentially improving kidney health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can pentoxifylline prevent renal disease? Wardle, EN.[2019]

In a study on diabetic nephropathy using streptozotocin-induced diabetic rats, prolonged administration of pentoxifylline (PTX) significantly reduced urinary protein levels after 8 weeks, indicating its effectiveness in preventing proteinuria.

PTX treatment also decreased markers of inflammation, such as MCP-1 and ED-1 positive cells, after 4 weeks, suggesting that PTX has both anti-inflammatory and renoprotective effects in diabetic nephropathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged administration enhances the renoprotective effect of pentoxifylline via anti-inflammatory activity in streptozotocin-induced diabetic nephropathy. Han, KH., Han, SY., Kim, HS., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11831249/

Pentoxifylline for diabetic kidney disease - PMC Compared with placebo, pentoxifylline significantly reduced serum creatinine (SCr), albuminuria, and overt proteinuria, but not creatinine clearance (CrCl).

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6463074/

Pentoxifylline for Renal Protection in Diabetic Kidney ... In the context of diabetic kidney disease, pentoxifylline has shown significant antiproteinuric effects and a delay in the loss of estimated glomerular ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03625648

NCT03625648 | Pentoxifylline in Diabetic Kidney Disease Recent experimental and clinical data suggest that PTX, when added to usual care in patients with DKD, leads to a reduction in albuminuria and reduced ...

4. academic.oup.com academic.oup.com/ckj/article/15/12/2200/6589427

pentoxifylline, an old drug and a new opportunity for diabetic ... [107] reported a 19.6% decrease in proteinuria in third month and improved graft survival by the end of the study in non-diabetic renal transplant recipients ...

5. bmcnephrol.biomedcentral.com bmcnephrol.biomedcentral.com/articles/10.1186/s12882-025-04399-3

The potential adding therapeutic effect of pentoxifylline and/or ... Our results demonstrated that administration of therapeutic doses of PTX and/or FA in CKD patients delayed the progression of advanced chronic ...

6. nephjc.com nephjc.com/pentoxifylline

Pentoxifylline for Diabetic Nephropathy Results: The eGFR fell by 2.1±0.4 ml/min per 1.73m2 in patients treated with pentoxifylline versus 6.5±0.4 ml/min per 1.73 m2 ...