Montelukast for Kidney Disease in Type 1 Diabetes

Overseen By Jessica Kendrick

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Colorado, Denver

Must be taking: Angiotensin inhibitors

Must not be taking: Corticosteroids, Beta agonists, others

Disqualifiers: Uncontrolled hypertension, Pregnancy, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if montelukast, a drug that blocks certain inflammatory chemicals, can slow kidney disease in people with type 1 diabetes. Researchers seek to discover if it can reduce protein levels in urine, an early sign of kidney damage. Participants will receive either montelukast or a placebo (a non-active pill) daily. Suitable candidates have had type 1 diabetes for over 5 years and experience increased protein in their urine. As a Phase 4 trial, this research explores how an already FDA-approved and effective treatment can benefit more patients.

Will I have to stop taking my current medications?

The trial requires that you have a stable dose of certain medications, like angiotensin converting enzyme inhibitors or angiotensin receptor blockers, for at least 4 weeks before starting. You cannot participate if you are using inhaled or systemic corticosteroids, long-acting beta agonists, phenobarbital, rifampin, or carbamazepine.

What is the safety track record for Montelukast?

Research has shown that montelukast, a medication often used for asthma, is usually safe and well-tolerated. Studies on diabetic rats suggest that montelukast can protect the kidneys, indicating potential benefits for kidney problems in people with type 1 diabetes. Notably, the FDA has already approved montelukast for other uses, which adds confidence about its safety in humans. Previous studies have not reported any major side effects. However, as with any medication, some risks may exist, so consulting a healthcare provider is always advisable. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Most treatments for kidney disease in Type 1 diabetes focus on managing blood pressure and blood sugar levels to slow kidney damage. But Montelukast works differently, targeting inflammation by blocking leukotrienes, compounds involved in inflammatory responses. Researchers are excited about Montelukast because it offers a new mechanism of action, potentially reducing kidney inflammation directly, which could be a game-changer in preserving kidney function. Plus, Montelukast is already approved for asthma, so its safety profile is well-documented, providing an additional layer of confidence for its use in this new indication.

What evidence suggests that montelukast might be an effective treatment for kidney disease in type 1 diabetes?

Research has shown that montelukast, which participants in this trial may receive, may help reduce kidney damage in diabetic rats. It seems to protect the kidneys by reducing inflammation and damage from harmful molecules called free radicals. In studies, montelukast improved kidney function in models of diabetic kidney disease. Reviews suggest it could be a safe and effective way to enhance kidney health. Based on these findings, montelukast might help with kidney disease in people with type 1 diabetes. ^{2 3 6 7 8}

Who Is on the Research Team?

Jessica Kendrick, MD

Principal Investigator

University of Colorado Denver | Anschutz

Are You a Good Fit for This Trial?

This trial is for adults aged 18-80 with type 1 diabetes for at least five years, showing early signs of kidney disease (protein in urine), and on a stable regimen of blood pressure medication and insulin. They should be sedentary or lightly active, not severely obese, and have moderately functioning kidneys. Excluded are those with other serious health issues, current study participants, uncontrolled hypertension, pregnant/breastfeeding women, certain drug users/allergies.

Inclusion Criteria

Able to provide consent

I have had Type 1 diabetes for 5 years or more.

My kidney function is moderately reduced.

Exclusion Criteria

You have a serious mental health condition in your past.

You have other serious health problems that make it likely for you to live less than 1 year.

My liver is severely damaged.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either montelukast or placebo daily to assess changes in kidney and vascular function

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Montelukast

Trial Overview The trial tests if Montelukast can reduce protein levels in the urine (a sign of kidney disease) and improve kidney/heart health in people with type 1 diabetes. Participants will either receive Montelukast or a placebo to compare effects.

How Is the Trial Designed?

Group I: Montelukast Experimental Treatment 1 Intervention

One 10mg capsule daily

Group II: Placebo Placebo Group 1 Intervention

One capsule daily

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

Approved in United States as Singulair for:

• Asthma
• Exercise-induced bronchoconstriction
• Allergic rhinitis

Approved in Canada as Singulair for:

• Asthma
• Exercise-induced bronchoconstriction
• Allergic rhinitis

Approved in European Union as Singulair for:

• Asthma
• Exercise-induced bronchoconstriction
• Allergic rhinitis

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

Published Research Related to This Trial

Diabetes significantly increases the risk of chronic kidney disease (CKD), and managing diabetes in CKD patients requires careful consideration of their unique treatment needs, including monitoring for complications like hypertension and dyslipidaemia.

Metformin is the preferred medication for diabetic patients with CKD, as long as their kidney function (eGFR) is above 30 mL/min, due to its effectiveness, low risk of hypoglycaemia, and associated health benefits, while other medications like sulfonylureas should be used cautiously due to a higher risk of hypoglycaemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diabetes treatment in patients with renal disease: Is the landscape clear enough? Ioannidis, I.[2021]

Montelukast, used as a monotherapy for 12 weeks in 50 children aged 3-11 with mild persistent asthma, significantly improved clinical scores and lung function, demonstrating its efficacy in managing asthma symptoms.

While the treatment was generally well-tolerated, mild side effects were reported in 19% of participants, including anorexia, elevated liver function tests, and headaches, indicating that while effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of montelukast as monotherapy in children with mild persistent asthma. Ghosh, G., Manglik, AK., Roy, S.[2021]

In a study of 5,586 diabetic patients with advanced chronic kidney disease (CKD), the use of short-acting meglitinides was found to significantly increase the risk of hypoglycemia, with a hazard ratio of 1.94.

The combination of meglitinides and insulin further heightened the risk of hypoglycemia (HR, 1.69), while hypoglycemia itself was a predictor of long-term mortality, indicating careful monitoring is needed for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meglitinides increase the risk of hypoglycemia in diabetic patients with advanced chronic kidney disease: a nationwide, population-based study. Wu, PC., Wu, VC., Lin, CJ., et al.[2019]

The EMPA-KIDNEY study evaluated the effects of empagliflozin in patients with chronic kidney disease, demonstrating significant benefits in slowing the progression of kidney disease.

This study involved a large cohort of patients, providing robust evidence for the efficacy of empagliflozin as a treatment option for chronic kidney disease, highlighting its potential to improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In CKD, once-daily empagliflozin reduced progression of kidney disease or CV death at 2 y. Kwong, YD., Hsu, CY.[2023]

Montelukast (MK), a selective cysteinyl leukotriene receptor antagonist, significantly reduced kidney damage in rats with experimental diabetes, as evidenced by decreased glomerular lesions and tubular injuries after 8 weeks of treatment.

The study involved four groups of adult male Wistar rats, with one group receiving MK daily for 8 weeks, showing that MK has a partially protective effect against renal damage caused by diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Montelukast influence on kidney in experimental induced diabetes mellitus. Gales, C., Stoica, B., Nechifor, M., et al.[2023]

In a study of 80 hemodialysis patients, montelukast significantly reduced the severity of uremic pruritus compared to placebo, as measured by both visual analogue scale and Detailed Pruritus Score over 30 days.

Montelukast also led to a decrease in high-sensitivity C-reactive protein levels, suggesting a potential anti-inflammatory effect, which may contribute to its efficacy in treating pruritus in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic Effect of Montelukast for Treatment of Uremic Pruritus in Hemodialysis Patients. Mahmudpour, M., Roozbeh, J., Raiss Jalali, GA., et al.[2021]

Montelukast treatment in grass-allergic patients significantly reduced eosinophil survival compared to placebo, indicating its effectiveness in managing asthma symptoms by affecting immune cell behavior.

The study found that montelukast suppressed the production of GM-CSF, a key cytokine that enhances eosinophil survival, suggesting that it works by inhibiting this cytokine's production from peripheral blood mononuclear cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of asthmatic patients with a cysteinyl leukotriene receptor-1 antagonist montelukast (Singulair), decreases the eosinophil survival-enhancing activity produced by peripheral blood mononuclear leukocytes in vitro. Becler, K., Håkansson, L., Rak, S.[2021]

In a study involving 16 patients with end-stage renal disease, montelukast sodium significantly reduced uremic pruritus by 35%, compared to only a 7% reduction with placebo, indicating its efficacy as a treatment option.

Despite some adverse events, including one death and a case of anemia, montelukast was generally well-tolerated, suggesting it may be a safe alternative for patients suffering from refractory pruritus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Montelukast for treatment of refractory pruritus in patients on hemodialysis. Nasrollahi, AR., Miladipour, A., Ghanei, E., et al.[2021]

In a case series of four diabetes patients with renal transplants, the SGLT-2 inhibitor dapagliflozin at a dose of 10 mg significantly improved hemoglobin A1c levels without negatively affecting renal function.

Dapagliflozin also had beneficial effects on blood pressure and weight, suggesting it can be a safe and effective option for managing diabetes in renal transplant patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful use of the sodium-glucose co-transporter-2 inhibitor dapagliflozin in patients with renal transplant and diabetes: a case series and literature review. Gul, W., Naem, E., Elawad, S., et al.[2022]

Patients with chronic kidney disease (CKD) often experience insulin resistance and metabolic disorders, making diabetes management particularly challenging due to the need for adjusted medication dosages as kidney function declines.

The Polish Society of Nephrology Working Group has issued recommendations for diagnosing and treating type 2 diabetes in CKD patients, highlighting the need for careful consideration of anti-diabetic medications to avoid increased risks of hypoglycemia and adverse drug reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnosis and treatment of type 2 diabetes mellitus in patients with chronic kidney disease and eGFR Stompór, T., Adamczak, M., Masajtis-Zagajewska, A., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10962779/

Evaluation of Effect of Montelukast in the Model ... Conclusion: Montelukast showed a protective effect in the model of diabetic nephropathy because of its antioxidant effect. Keywords: Diabetic mellitus, ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10907471/

Ameliorative effect of montelukast against STZ induced ... The current study explored the renoprotective impact of montelukast (Mon) against streptozotocin (STZ)-induced DN in rats compared to a standard ...

3. withpower.com withpower.com/trial/montelukast-for-kidney-disease-in-type-1-diabetes-7e73f

Montelukast for Kidney Disease in Type 1 Diabetes Research on Montelukast shows it can reduce kidney damage in diabetic rats, suggesting it might help with kidney issues in Type 1 Diabetes. Additionally, ...

4. journals.lww.com journals.lww.com/indjem/fulltext/2024/01000/evaluation_of_effect_of_montelukast_in_the_model.9.aspx

Evaluation of Effect of Montelukast in the Model of... CONCLUSION. In the present study, Montelukast showed a potential renoprotective effect as evident from the assessment of renal biochemical and ...

5. journals.lww.com journals.lww.com/annals-of-medicine-and-surgery/fulltext/2024/06000/the_renoprotective_potential_of_montelukast__a.55.aspx

The renoprotective potential of montelukast: a scoping review The review confirms that montelukast is a safe and effective choice for improving renal function, supported by the review of several research ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05498116

Effect of Montelukast on Kidney and Vascular Function in ... The current proposal will investigate whether montelukast, a leukotriene blocker, lowers increased levels of protein in the urine (an early marker of diabetic ...

7. renalandurologynews.com renalandurologynews.com/reports/asthma-drugs-leukotriene-antagonists-linked-lower-kidney-failure-risk/

Drugs Used to Treat Asthma Linked to Lower Kidney ... “Our group is currently conducting a clinical trial of montelukast vs. placebo on kidney outcomes in patients with type 1 diabetes.

8. frontiersin.org frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1153653/full

Evaluating the safety and efficacy of the leukotriene ... Montelukast adjuvant therapy was superior to metformin-only therapy in diabetes control and weight loss, most likely due to its increased insulin sensitivity ...