Official Title: “Autoregulation of Glomerular Filtration Rate in Patients With Type 1 Diabetes During Spironolactone Therapy”

To evaluate the impact of spironolactone treatment on renal autoregulation in hypertensive type 1 diabetic patients.

Study Type: Interventional

Study Design: Treatment, Randomized, Double-Blind, Placebo Control, Crossover Assignment, Safety/Efficacy Study

Double-masked, randomized, crossover trial. In random order, patients will be treated with spironolactone 25 mg o.d. and matched placebo for 28 days.

On the last day of treatment, GFR will be determined twice on the same day: first without clonidine and secondly after injection of clonidine (clonidine induces a transient reduction in blood pressure, with no influence on renal plasma flow and GFR), in order to evaluate the effect of antihypertensive treatment with spironolactone on renal autoregulation of GFR. The study will be preceded by a wash-out period of 1 month for patients receiving antihypertensive medication. Patients will be instructed to measure blood pressure twice daily, three days a week during this period. If, during the washout period, blood pressure exceeds 170/105 mm Hg or persistent edemas develop, treatment with long-acting loop diuretics will be initiated and continued throughout the rest of the study. If blood pressure despite diuretic treatment still exceeds 170 mm Hg systolic and/or 105 mm Hg diastolic, the patient will be excluded from the study and previous/appropriate antihypertensive treatment will be restarted.

Intervention(s) in this Clinical Trial

• Drug: Spironolactone

Primary Measures

• Changes in glomerular filtration rate

Secondary Measures

• Changes in blood pressure
• Changes in albuminuria
• Changes in fractional albumin clearance

Inclusion Criteria:

• Type 1 diabetes
• Age between 18 and 70 years
• Blood pressure ≥ 135 mm Hg systolic and/or ≥ 85 mm Hg diastolic or ongoing antihypertensive treatment
• Informed consent

Exclusion Criteria:

• Diabetic nephropathy
• Other known kidney or renal tract disease
• Malignant hypertension
• Blood pressure > 170/105 at baseline or during AHT wash-out period
• Plasma potassium > 4.7 mmol/l
• Elevated plasma creatinine (>88 µmol/l for women and >100 µmol/l for men)
• Symptoms of Ischemic heart disease within 3 months prior to study start
• Previous cerebrovascular event (apoplexy, TCI)
• Abuse of medicine or alcohol
• Pregnancy or breastfeeding
• Woman of child-bearing age who are not using adequate contraception
• ASA treatment > 1g/day or regular use of NSAIDs
• Known allergy to or side-effects of spironolactone
• Inability to understand patient information

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 70 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Steno Diabetes Center

Overall Clinical Trial Officials and Contacts

Hans-Henrik Parving, MD,DMSc,Prof Principal Investigator Steno Diabetes Center  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00335413

Study ID Number: 2006-001453-10

ClinicalTrials.gov Identifier: NCT00335413

Health Authority: Denmark: Ethics Committee