Pentoxifylline for Diabetic Kidney Disease

(PTXRx Trial)

Recruiting at 34 trial locations

Overseen By Cheryl C Odle, MBA

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: VA Office of Research and Development

Must not be taking: Pentoxifylline, Ketorolac, Riociguat

Disqualifiers: Type 1 diabetes, Organ transplant, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

Pentoxifylline (PTX) is a medication that has been on the market since 1984 for use in disease in the blood vessels of the legs. There is some preliminary information that it may protect the kidneys from damage due to diabetes and other diseases. "Pentoxifylline in Diabetic Kidney Disease" is a study to bee conducted in 40 VA hospitals across the nation to determine definitively whether or not PTX can prevent worsening of kidney disease and delay death in patients with diabetic kidney disease.

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 data supports the effectiveness of the drug pentoxifylline for diabetic kidney disease?

Research shows that pentoxifylline can reduce proteinuria (excess protein in urine) and improve kidney function in diabetic patients by reducing inflammation and improving blood flow. Long-term use has also been associated with improvements in diabetic vascular complications, suggesting it may help slow the progression of kidney disease. ^{1 2 3 4 5}

Is pentoxifylline safe for humans?

Pentoxifylline is generally considered safe for humans, with most studies reporting only minor stomach-related side effects. ^{2 3 4 6 7}

How does the drug pentoxifylline differ from other treatments for diabetic kidney disease?

Pentoxifylline is unique because it has anti-inflammatory and antifibrotic properties, which may help reduce proteinuria (excess protein in urine) and improve kidney function in diabetic patients. Unlike standard treatments, it also improves blood flow by enhancing blood cell flexibility, potentially offering additional benefits for diabetic kidney disease. ^{2 3 5 6 8}

Research Team

David J Leehey

Principal Investigator

Edward Hines Jr. VA Hospital, Hines, IL

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Pentoxifylline (Other)
• Placebo (Other)

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.

Participant Groups

Group I: PTX Experimental Treatment 1 Intervention

Active drug

Group II: Placebo Placebo Group 1 Intervention

Placebo

Pentoxifylline is already approved in Canada for the following indications:

Approved in Canada 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+

Findings from Research

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]

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 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 (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 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]

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]

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 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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Prolonged administration enhances the renoprotective effect of pentoxifylline via anti-inflammatory activity in streptozotocin-induced diabetic nephropathy. [2021]

2. England pubmed.ncbi.nlm.nih.gov

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

3. United States pubmed.ncbi.nlm.nih.gov

The effect of pentoxifylline on proteinuria in diabetic kidney disease: a meta-analysis. [2018]

4. Netherlands 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. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Effect of pentoxifylline on microalbuminuria in diabetic patients: a randomized controlled trial. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Can pentoxifylline prevent renal disease? [2019]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Effect of pentoxifylline on renal outcomes in chronic kidney disease patients: A systematic review and meta-analysis. [2018]

8. Italy 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. [2019]