Colchicine for Chronic Kidney Disease

Overseen By Leo F Buckley, PharmD MPH

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Brigham and Women's Hospital

Must be taking: ACE inhibitors, SGLT2 inhibitors

Must not be taking: Immunosuppressives, Antimicrobials, P-gp inhibitors, CYP3A4 inhibitors

Disqualifiers: Heart failure, Kidney failure, Malignancy, 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: Unknown

Duration: 4 weeks

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness and safety of colchicine for individuals with chronic kidney disease. Participants will receive either colchicine, which may reduce inflammation, or a placebo, which contains no active ingredients, to compare their effects. The trial targets those with reduced kidney function who manage their condition with specific medications. Individuals with chronic kidney issues on stable medications may qualify for this study. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as immunosuppressive or anti-inflammatory drugs, systemic antimicrobial therapy, and medications that may cause muscle problems. If you are taking any of these, you may need to stop them at least 30 days before joining the study.

Is there any evidence suggesting that colchicine is likely to be safe for humans?

Research has shown that colchicine, in lower doses, is usually safe for people with severe chronic kidney disease (CKD). It helps manage arthritis flare-ups caused by crystals in this group. However, detailed studies on colchicine specifically for CKD remain limited. Despite this, available information suggests careful use of colchicine in people with CKD. Always consult a healthcare provider about any concerns before deciding to join a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for chronic kidney disease?

Unlike the standard treatments for chronic kidney disease, which often focus on managing blood pressure and diabetes or using medications like ACE inhibitors and ARBs, colchicine offers a novel approach. Colchicine is known for its anti-inflammatory properties, which could potentially reduce inflammation in the kidneys, a key factor in the progression of chronic kidney disease. Researchers are excited because colchicine acts on a different pathway, providing a new mechanism that might slow kidney damage more effectively than current options.

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

Studies have shown that colchicine can benefit people with chronic kidney disease (CKD). In patients with severe CKD and arthritis from crystal buildup, colchicine effectively reduced flare-ups 83% of the time and was well tolerated, managing symptoms without major side effects. Additionally, colchicine's ability to reduce inflammation is known to lower the risk of heart problems in people with heart disease. Research also shows that taking a low dose of colchicine is safe for long-term use. These findings suggest that colchicine, which participants in this trial may receive, could be a promising treatment for chronic kidney disease. ^{1 3 4 6 7}

Who Is on the Research Team?

Leo F Buckley, PharmD MPH

Principal Investigator

Brigham and Women's Hospital

Are You a Good Fit for This Trial?

Adults aged 21-80 with chronic kidney disease, inflammation (high C-reactive protein levels), and heart strain are eligible. They must be able to consent, follow the study plan, have an eGFR of 15-75 mL/min/1.73 m2, and a high urine albumin level. Exclusions include colchicine allergy, recent hospitalization or surgery, severe heart failure or other serious conditions that increase risk.

Inclusion Criteria

My doctor thinks I should take a medication for sugar control in my blood.

Your heart function was very weak in the past year.

My kidney function, measured by eGFR, is between 15 to 75 mL/min.

Exclusion Criteria

I have a heart condition I was born with.

You have a serious illness or condition that makes the doctor think participating in the study could be risky for you.

I have had surgery in the last 30 days or will have it during the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive colchicine or placebo once daily to assess efficacy and safety

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Colchicine

Trial Overview The trial is testing if colchicine can safely reduce inflammation in patients with chronic kidney disease compared to a placebo. Participants will either receive colchicine or a placebo pill without knowing which one they're getting to measure the true effect of the drug.

How Is the Trial Designed?

Group I: Colchicine Experimental Treatment 1 Intervention

Colchicine 0.3 mg once daily

Group II: Placebo Placebo Group 1 Intervention

Placebo once daily

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

Approved in United States as Colcrys for:

• Gout
• Familial Mediterranean Fever

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

Chronic kidney disease (CKD) is a significant health issue in Croatia, with high management costs for patients in end-stage CKD, highlighting the need for effective early detection and management strategies.

Currently, there is no drug to stop the progression of CKD, so the focus is on screening, specific therapies, and managing complications, emphasizing the importance of patient compliance and education for both healthcare providers and the public.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[What do we know about chronic kidney disease at the beginning of the 21st century?]. Kes, P.[2018]

In a retrospective study involving 155 patients with chronic glomerulonephritis, therapies combining cytostatics, platelet aggregation inhibitors, and anticoagulants (CAA-therapy) showed favorable results, particularly in cases of nephrotic syndrome and glomerulonephritis with significant clinical symptoms.

Additional prednisone therapy (CAAP-therapy) also demonstrated effectiveness, while patients with clinically inactive nephritis and only urinary findings did not respond to these treatments, indicating that the therapy is most beneficial for active disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New results concerning the effectiveness of therapy of chronic glomerulonephritis. Results of cytostatics-anticoagulants-aggregation inhibitors, cystostatics-anticoagulants-aggregation inhibitors-prednisone and cystostatics-prednisone therapy, derived from a retrospective study]. Sinn, W., Ratner, M., Tomilina, N., et al.[2013]

A nationwide study of 10,805 patients with advanced chronic kidney disease found that UVB phototherapy did not increase the risk of developing skin cancer compared to those who did not receive UVB treatment, even after a median follow-up of 75 months.

Patients receiving more UVB phototherapy also showed no increased risk of skin cancer, suggesting that UVB treatment is a safe option for managing uraemic pruritus in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of Skin Cancer among Patients with Chronic Kidney Disease Treated with Ultraviolet B Phototherapy for Uraemic Pruritus: A Nationwide Cohort Study. Ko, MJ., Huang, JW., Wu, HY., et al.[2022]

Chronic kidney disease (CKD) affects about 10% of the population, with diabetes being the most common cause, and it significantly increases the risk of cardiovascular events, dialysis dependency, and mortality as kidney function declines.

Current guidelines recommend that patients with a glomerular filtration rate (GFR) of ≤30 or ≤60 ml/min/1.73 m², especially with additional risk factors, should be referred to a nephrologist, highlighting the importance of early intervention in CKD management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[What is confirmed in the treatment of chronic kidney disease?] Greite, R., Schmidt-Ott, K.[2022]

A large study of over 1.5 million Taiwanese patients with chronic kidney disease (CKD) found that they have a 1.14-fold increased risk of developing non-melanoma skin cancer (NMSC) compared to the general population.

The risk is particularly high in pre-dialysis stage 5 CKD patients, especially those with anemia (1.48-fold increase) and those experiencing uraemic pruritus after long-term antihistamine treatment (1.38-fold increase).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of Non-melanoma Skin Cancer in Patients with Chronic Kidney Disease and its Relationship to Uraemic Pruritus. Wang, CC., Tang, CH., Huang, SY., et al.[2022]

A 39-year-old man on hemodialysis for chronic renal failure developed skin lesions consistent with porphyria cutanea tarda (PCT), with significantly elevated plasma porphyrins, particularly uroporphyrin, indicating a potential link between hemodialysis and PCT.

The study suggests that the increase in plasma porphyrins in patients undergoing hemodialysis may not be solely due to inadequate clearance, but could involve factors affecting the enzyme uroporphyrinogen decarboxylase, highlighting a possible mechanism of action in this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Porphyria cutanea tarda in a chronic hemodialysis patient]. Kano, T., Yamane, Y., Suzuki, M., et al.[2011]

The patient exhibited symptoms consistent with hereditary coproporphyria, including elevated levels of specific porphyrin metabolites, and a significant reduction in coproporphyrinogen oxidase activity, which is crucial for porphyrin metabolism.

Molecular analysis identified a novel mutation in the coproporphyrinogen oxidase gene, confirming the hereditary nature of the condition in the patient's family, as all affected relatives showed similar biochemical abnormalities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular, immunological, enzymatic and biochemical studies of coproporphyrinogen oxidase deficiency in a family with hereditary coproporphyria. Gross, U., Puy, H., Kühnel, A., et al.[2006]

In two female patients undergoing prolonged maintenance hemodialysis, the development of blisters and postbullous erosions was observed, indicating potential skin complications associated with this treatment.

One patient exhibited elevated levels of uroporphyrin I and III in the urine, suggesting a possible link between hemodialysis and porphyrin metabolism disturbances.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Porphyria cutanea tarda-like aspects in two prolonged hemodialysis patients (author's transl)]. Korting, GW.[2006]

In a study of 98 hypertensive patients with chronic kidney disease (CKD), antihypertensive therapy significantly improved their estimated glomerular filtration rate (eGFR) from 51.87 to 57.55 mL/min/1.73 m² over 3 years (P<.001).

In contrast, eGFR decreased in patients without CKD, indicating that antihypertensive therapy specifically benefits those with CKD by preventing further decline in kidney function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Estimated glomerular filtration rate reversal by blood pressure lowering in chronic kidney disease: Japan Multicenter Investigation for Cardiovascular DiseaseB CKD study. Yui, Y., Kodama, K., Hirayama, A., et al.[2021]

A systematic review of glomerulonephritis management emphasizes the importance of tailored treatment based on histological type, with specific recommendations for conditions like IgA nephropathy, minimal change nephropathy, and membranous nephropathy, based on extensive literature analysis.

For minimal change nephropathy and focal segmental glomerulosclerosis, initial treatment in children typically involves prednisone, while adults may experience slower responses but fewer relapses, highlighting the need for age-specific treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Instructions and implementations for percutaneous renal biopsy. Guidelines for the therapy of glomerular nephropaties]. Cagnoli, L.[2017]

Citations

1. rmdopen.bmj.com rmdopen.bmj.com/content/10/1/e003872

Safety and efficacy of colchicine in crystal-induced arthritis ... The use of colchicine, at reduced dosage, in patients with crystal-induced arthritis flare and severe CKD was effective (83%) and well tolerated ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06998862

Colchicine in Chronic Kidney Disease Patients Its main objective is to demonstrate the benefit of low-dose colchicine treatment in secondary prevention of cardiovascular events in patients with moderate ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2021372

Colchicine in Patients with Chronic Coronary Disease Evidence from a recent trial has shown that the antiinflammatory effects of colchicine reduce the risk of cardiovascular events in patients with recent ...

4. rheumatologyadvisor.com rheumatologyadvisor.com/home/topics/gout/low-dose-colchicine-effective-for-managing-cppd-disease-flares-in-severe-ckd/

Low-Dose Colchicine Well Tolerated for Managing Crystal ... Colchicine may be used with caution to manage flare-ups of crystal-induced arthritis among patients with severe chronic kidney disease (CKD).

5. amjmed.com amjmed.com/article/S0002-9343(21)00510-6/fulltext

Consensus Statement Regarding the Efficacy and Safety of ... Further, data accrued over the last 50 years strongly suggest that the biologic effects of long-term colchicine do not increase the risk of ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38296804/

Safety and efficacy of colchicine in crystal-induced arthritis ... The use of colchicine, at reduced doses, was mostly effective to treat crystal-induced arthritis flare in 54 patients with severe CKD and was well tolerated.

7. bhm.scholasticahq.com bhm.scholasticahq.com/article/123647-complications-of-colchicine-initiation-in-a-patient-with-chronic-kidney-disease

Complications Of Colchicine Initiation in a Patient with Chronic ... Unfortunately, research into the safety of colchicine in patients with severe CKD is lacking, as most clinical trials exclude patients with CrCl ...