Fenofibrate for Type 1 Diabetes

(PERL-FENO Trial)

Recruiting at 3 trial locations

Overseen By Christine Mendonca

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Alessandro Doria

Must be taking: Insulin, RASB

Must not be taking: Fibrates, PPAR-α agonists

Disqualifiers: Renal transplant, Dialysis, Cancer, 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: 76 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

Diabetic kidney disease remains the leading cause of end-stage kidney disease (ESKD), rising in frequency in parallel with the epidemic of diabetes worldwide. The estimated lifetime risk of kidney disease in persons with type 1 diabetes (T1D) has been reported to be as high as 50-70%, although risk may be lower in excellent care environments. Two previous studies have suggested that a generic drug used to lower fats in blood (fenofibrate) may protect the kidney from damage due to diabetes. These data, however, were obtained among people with type 2 diabetes with clinical characteristics optimized for cardiovascular studies. Thus, a clinical trial specifically designed to evaluate the effects on the kidney is required to firmly show that this drug can prevent kidney damage in T1D. The goals of the present pilot study are to demonstrate the feasibility of such trial, gather essential information for designing and planning this study, and generate preliminary data. To this end, 40 participants with T1D and early-to-moderate diabetic kidney disease (DKD), at high risk of ESKD, will be enrolled at two clinical sites and assigned in a 1:1 ratio to treatment with fenofibrate or placebo for 18 months. Kidney function will be measured at the beginning and at the end of the study to evaluate the effect of fenofibrate.

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 taking fibrates or other similar drugs. You should discuss your specific medications with the trial team to be sure.

Is fenofibrate safe for use in humans?

Fenofibrate has been used safely in humans for conditions like high cholesterol and triglycerides, with studies showing it is generally well tolerated. In trials, it has been used alone or in combination with other drugs without serious adverse effects, and it has shown potential benefits for cardiovascular and microvascular health. ^{1 2 3 4 5}

How does the drug fenofibrate differ from other treatments for type 1 diabetes?

Fenofibrate is unique for type 1 diabetes because it may help some patients reduce or eliminate their need for insulin by improving the body's natural ability to control blood sugar. This is different from standard treatments that typically focus on insulin replacement. ^{1 2 6 7 8}

What evidence supports the effectiveness of the drug fenofibrate for type 1 diabetes?

A case study showed that a 19-year-old with newly diagnosed type 1 diabetes became insulin-independent after starting fenofibrate, suggesting it might help manage blood sugar levels in type 1 diabetes. ^{2 6 7 8 9}

Who Is on the Research Team?

Alessandro Doria, MD PhD MPH

Principal Investigator

Joslin Diabetes Center

Michael Mauer, MD

Principal Investigator

University of Minnesota

Are You a Good Fit for This Trial?

Adults aged 18-70 with Type 1 Diabetes and early-to-moderate kidney disease at high risk of progressing to end-stage kidney disease. Participants must have been treated with insulin within a year of diagnosis, have specific levels of kidney function, and be willing to follow the study plan. Exclusions include other health conditions like non-diabetic kidney diseases, allergies to fibrates or iodine, recent blood donations, pregnancy without contraception use, drug abuse history, certain medical histories including pancreatitis and cancer treatments.

Inclusion Criteria

I have diabetic kidney disease at high risk of worsening.

You have had type 1 diabetes for at least 8 years.

My kidney function, measured by eGFR, is between 40 and 99.9.

Exclusion Criteria

I have had gallstones but my gallbladder has been removed.

Your hemoglobin (a protein in red blood cells) level is too low (less than 11 g/dL for males, less than 10 g/dL for females) or your platelet count is too low (less than 100,000/mm3) at the time of screening.

My kidney disease is not caused by diabetes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive either fenofibrate or placebo for 18 months

76 weeks

Washout

Participants undergo a two-month washout period to assess the effects of discontinuing the treatment

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Fenofibrate

Trial Overview The trial is testing whether fenofibrate can prevent further damage in kidneys affected by diabetes in people with Type 1 Diabetes. Forty participants will either receive fenofibrate or a placebo for 18 months at two clinical sites. The main goal is to see if there's an improvement in their kidney function compared to those who just get the placebo.

How Is the Trial Designed?

Group I: Fenofibrate Experimental Treatment 1 Intervention

145 mg oral fenofibrate daily for 76 weeks. Dosage is decreased to 48 mg daily if iGFR is or is estimated to be below 30 ml/min/1.73 m2.

Group II: Placebo Placebo Group 1 Intervention

Inactive tablets identical to fenofibrate

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

Approved in United States as Fenofibrate for:

• High cholesterol
• Severe high triglycerides

Approved in European Union as Fenofibrate for:

• Mixed hyperlipidemia
• Primary hypercholesterolemia
• Severe hypertriglyceridemia

Approved in Canada as Fenofibrate for:

• Hyperlipidemia
• Hypertriglyceridemia

Who Is Running the Clinical Trial?

Alessandro Doria

Lead Sponsor

Trials

3

Recruited

720+

University of Minnesota

Collaborator

Trials

1,459

Recruited

1,623,000+

University of Michigan

Collaborator

Trials

1,891

Recruited

6,458,000+

Published Research Related to This Trial

Type 2 diabetic patients on statins who had high triglycerides and low HDL cholesterol saw a 31% reduction in cardiovascular events when fenofibrate was added to their treatment.

This means that for every 20 patients treated with fenofibrate over five years, one cardiovascular event could be prevented, highlighting its efficacy in this specific patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ACCORD LIPID study results strengthen guideline approach of adding fenofibrate to therapy of dyslipidaemic type 2 diabetic patients. Aalbers, J.[2013]

In a study of 31 type 2 diabetic patients, fenofibrate treatment significantly improved glycemic control by lowering fasting and postprandial blood glucose levels, as well as reducing fasting serum insulin and leptin levels over 3 months.

Fenofibrate also effectively reduced triglyceride levels and increased HDL cholesterol, demonstrating its benefits for both lipid profiles and insulin resistance, while being well tolerated by all participants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fenofibrate treatment is associated with better glycemic control and lower serum leptin and insulin levels in type 2 diabetic patients with hypertriglyceridemia. Damci, T., Tatliagac, S., Osar, Z., et al.[2022]

Citations

1. South Africa pubmed.ncbi.nlm.nih.gov

ACCORD LIPID study results strengthen guideline approach of adding fenofibrate to therapy of dyslipidaemic type 2 diabetic patients. [2013]

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

Insulin Independence in Newly Diagnosed Type 1 Diabetes Patient following Fenofibrate Treatment. [2020]

3. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Expediency of the use of fibrates for primary and secondary prevention of cardiovascular complications.]. [2018]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Fenofibrate treatment is associated with better glycemic control and lower serum leptin and insulin levels in type 2 diabetic patients with hypertriglyceridemia. [2022]

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

Long-term fenofibrate therapy increases fibroblast growth factor 21 and retinol-binding protein 4 in subjects with type 2 diabetes. [2013]

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

Summarizing the FIELD study: lessons from a 'negative' trial. [2013]

7. England pubmed.ncbi.nlm.nih.gov

Fibrates after the FIELD study: Some answers, more questions. [2015]

8. England pubmed.ncbi.nlm.nih.gov

Combination therapy with metformin and fenofibrate for insulin resistance in obesity. [2017]

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

Saroglitazar is noninferior to fenofibrate in reducing triglyceride levels in hypertriglyceridemic patients in a randomized clinical trial. [2022]