The Effect of Uric Acid Lowering in Type 1 Diabetes
Type 1 Diabetes Mellitus
About this trial
This is an interventional treatment trial for Type 1 Diabetes Mellitus focused on measuring Diabetic Nephropathy, Diabetes Mellitus, Diabetes Complications, Uric Acid, Febuxostat, Uloric, Glomerular Filtration Rate, Kidney Disease, Vascular Disease, Cardiovascular Diseases, Endothelial Function, Arterial Stiffness, Pharmacologic Actions, Gout Suppressants, Therapeutic Uses, Free Radical Scavengers, Antioxidants, Protective Agents, Physiological Effects of Drugs, Angiotensin II Infusion, Flow-mediated Dilation, Flow-mediated Constriction, Nitroglycerin, Hyperglycemia, Renin-angiotensin-aldosterone System, Nitric Oxide, cGMP, Oxidative Stress, Renal Haemodynamic Function, Inulin Clearance, PAH Clearance, Skin Biopsy, T1R mRNA Expression, Cytokines, Chemokines
Eligibility Criteria
Inclusion Criteria:
- Age 18-40 years old
- Normoalbuminuria 24 hour urine collection
- Body mass index 18-30 kg/m2 at screening
- Subject able, willing to perform assessments
- Normal electrocardiogram
- Normal renal (estimated GFR>60 ml/min)
- Clinic blood pressure <140/90 mmHg
- Type 1 DM, duration of diabetes >1 years
- Able to take medications every day
- Signed and dated written informed consent on the screening visit in accordance with GCP and local legislation
- Hemoglobin A1c 6-11%
- Normal uric acid levels
Exclusion Criteria:
- Cardiac, lung or peripheral vascular disease or stroke, gout
- Hypertension, or on BP-lowering medicine
- History of proliferative retinopathy
- Diagnosis of brittle diabetes based on investigator judgement
- Allergy to either allopurinol or probenecid
- Pregnancy, breastfeeding, no reliable contraception
- Oral contraceptives (due to effects on the RAS)
- Alcohol or tobacco within 24 hours prior to the study
- Uric acid ≥420 μmol/L or taking uric acid lowering agents
- Use of agents that influence GFR or interfere with purine metabolism (didanosine, azothioprine, methotrexate, NSAIDs, mycophenolate)
- Pancreas, pancreatic islet cells or renal transplant recipient
- Medical history of cancer or treatment for cancer in the last five years prior to screening
- T1DM treatment with any other drugs to reduce blood glucose except insulin within 6 months prior to screening (example: off-label use of metformin)
- Known autonomic neuropathy and proliferative retinopathy including treated proliferative retinopathy. Subjects with mild non-proliferative diabetic retinopathy can be included
- Alcohol or drug abuse within the three months prior to informed consent that would interfere with trial participation based on investigator judgement or any ongoing clinical condition that would jeopardize subject safety or study compliance based on investigator judgement
- ACE inhibitors, angiotensin receptor blockers, direct renin inhibitors, aldosterone antagonists
- Indication of liver disease, defined by serum levels of either alanine transaminase (ALT) (SGPT), aspartate transaminase (AST) (SGOT), or alkaline phosphatase above 3 x upper limit of normal (ULN) as determined during screening
- Blood disorders causing hemolysis or unstable red blood cells (e.g. malaria, hemolytic anemia)
- Pre-menopausal women (last menstruation ≤ 1 year prior to informed consent) who are nursing or pregnant or are of child-bearing potential and are not practising an acceptable method of birth control, or do not plan to continue using this method throughout the study.
- Participation in another trial with an investigational drug within 30 days prior to informed consent
Sites / Locations
- Renal Physiology Laboratory, University Health Network
Arms of the Study
Arm 1
Experimental
Febuxostat (trade name Uloric®)
Oral tablet, 80mg, OD, 8 weeks