Effects of Fenofibrate Therapy in Diabetic Nephropathy

• Status: Recruiting
• Trial end date: 2021-04-30
• Target enrollment: 0
• Participant gender: All

Summary

Diabetic nephropathy (DN) is a common cause of end-stage renal disease (ESRD) and accounts for nearly half of all new patients starting dialysis in Singapore, the country with the highest rates of DN in the Asia-Pacific region. Despite the scale of the problem, little progress has been made in our understanding of the pathogenesis of the disorder and no new therapies have been offered.

The investigators have conducted a metabolomics study of human diabetic nephropathy that revealed evidence for alterations in mitochondrial fuel metabolism in patients with the disease, a finding also reported in other recent studies of human DN. Based on this finding the investigators believe that dysregulated mitochondrial fuel oxidation is a major driver of diabetic nephropathy.

Fenofibrate is an agonist of peroxisome-proliferator activating receptor (ppar)-alpha that is approved for the treatment of hypercholesterolaemia and hypertriglyceridemia alone or combined in patients unresponsive to dietary and other non-drug therapeutic measures. Fenofibrate is also indicated for the reduction in the progression of diabetic retinopathy in patients with type 2 diabetes and existing diabetic retinopathy. Presently fenofibrate is not indicated for the treatment of diabetic nephropathy.

The investigators hypothesize that treatment with fenofibrate, taken orally at 300mg per day or 100mg per day for 30 days will lead to significant changes in the circulating metabolomics patterns in patients with DN. The investigators propose to administer the drug for a period of 30 days and will perform a comprehensive analysis of the state of fuel metabolism in these patients before, and after the administration of fenofibrate using targeted metabolomics and other approaches. Fundal photography, Optical Coherence Tomography (OCT) and Optical Coherence Tomography Angiography (OCTA) will also be performed at baseline and post-treatment. A total of 300 subjects will be recruited from Singapore General Hospital (SGH) Diabetes and Metabolic Centre. Our goal is to discover key changes in fuel metabolism in DN patients receiving fenofibrate.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Singapore General Hospital
• Collaborator: National Medical Research Council (NMRC), Singapore
• Treatments: Fenofibrate

Criteria

Inclusion Criteria:

• Man or woman between 21 and 100 years of age

• Type 2 diabetes mellitus Increased urine protein excretion as defined as:

• More than one measurement in the past 1-year with urine microalbumin/creatinine ratio (ACR) > 3.3 mg/mmol creatinine, or urine total protein/creatinine ratio (PCR) > 0.2 g/urine creatinine, or creatinine clearance between 30-60 ml/min

More than one measurement in the past 1-year with urine microalbumin/creatinine ratio (ACR) > 3.3 mg/mmol creatinine or urine total protein/creatinine ratio (PCR) > 0.2 g/urine creatinine

• Known diabetes duration > 3 months

• HbA1c < 9%(within 3 months prior to enrolment)

• No change in dose of diabetes medications by more than two-fold or new agents added within the previous 3 months

• No change in dose of lipid-lowering medications by more than two-fold or new agents added within the previous 3 months

• Capable of providing informed consent

Exclusion Criteria

• Type 1 diabetes mellitus

• Known intolerance or allergic to statins

• Known intolerance or allergic to fenofibrate

• Known intolerance or allergic to peanut oil or soybean lecithin or related products

• Concurrent use of fibrates

• Concurrent use Colchicine

• Concurrent use Nicotinic Acid

• Concurrent use Cyclosporine

• Concurrent use Tacrolimus

• Concurrent use Amodiaquine

• Concurrent use Bile acid sequestrants

• Concurrent use Chenodiol

• Concurrent use Ciprofibrate

• Oral anticoagulants: vitamin K antagonist (e.g. warfarin), factor Xa inhibitors (eg. rivaroxaban, apixaban and dabigatran)

• Concurrent use Anti-obesity medications (e.g. phentermine, orlistat)

• Concurrent use Systemic steroids (e.g. prednisolone, hydrocortisone, dexamethasone)

• Hepatitis B

• Hepatitis C

• Autoimmune hepatitis

• Hemochromatosis

• Previous pancreatitis

• Serum alanine aminotransferase or aspartate aminotransferase above 2x upper limit of normal

• Serum creatinine kinase above upper limit of normal

• Creatinine clearance < 30 ml/min

• Renal replacement therapy

• Presence of any non-DN renal glomerular disease

• Any previous organ transplantation

• Previous bariatric surgery

• Gallbladder disease

• Untreated hypothyroidism

• Untreated thyrotoxicosis

• Hemoglobin < 10 g/L

• Any leukopenia

• Any thrombocytopenia)

• Cancer within the last 5 years (except basal cell carcinoma)

• Medical condition likely to limit survival to less than 3 years

• Currently participation in another clinical trial

• Pregnancy, or currently trying to become pregnant

• Nursing mothers

• Hospitalization within 1 month prior to enrolment

• Alcohol intake > 1 unit per day for women or > 2 units per day for men

• Any factors likely to limit adherence to interventions

• Any ongoing acute medical illness

• Failure to obtain informed consent from participant