Blockade of Aldosterone Receptors as promising treatment for Type-1 Diabetes

Phase 4

• Conditions: Type 1 diabetes; Metabolic and Endocrine - Diabetes; Cardiovascular - Other cardiovascular diseases; Eye - Diseases / disorders of the eye

• Registration Number: ACTRN12613001355763
• Lead Sponsor: Pfizer Australia and New Zealand

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2013-12-11
• Last Update Posted: 13 January 2020

Recruitment & Eligibility

• Status: ot yet recruiting
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

1. Confirmed diagnosis of Type 1 diabetes for at least 10 years prior to informed consent;
2. Male and female participants must have optimal dose, or maximally tolerated dose of standard diabetes medication including ACE inhibitors/ARBs and diuretics (documented) such that minimal or no dose changes of other medications are required;
3. HbA1c greater than or equal to 7.0% and less than or equal to 9% at Visit 1 before entering the treatment period;
4. Mild non-proliferative retinopathy at Visit 1;
5. Participants must have ability to swallow pills.
6. Signed and dated written informed consent by date of Visit 1 in accordance with Good Clinical Practice (GCP) and local legislation.

Group 2: Control Group of healthy participants

- must not have been diagnosed with diabetes (type 1 or 2);
- have stable metabolic control (BP, lipids, blood sugar levels);
- Age 18-50 years;
- signed and dated written informed consent in accordance with Good Clinical Practice (GCP) and local legislation.

Exclusion Criteria

1. Serum potassium level greater than 5.0 mmol/l;
2. Indication of renal dysfunction defined by serum creatinine greater than 220 µmol/L;
3. Indication of impaired renal function, defined as estimated glomerular filtration rate (eGFR) less than 45 ml/min/1.73m2;
4. Participants who have known allergy to aldosterone receptor antagonists or are currently taking an aldosterone receptor antagonist;
5. Participants enrolled in other trials or participation in the follow-up period of another trial;
6. Participants who have a contra-indication to cardiac MRI, including administration of gadolinium-based IV contrast;
7. Indication of liver disease, defined by serum levels of either ALT (SGPT), AST (SGOT), or alkaline phosphatase above 3 x upper limit of normal (ULN) as determined during Visit 1;
8. Participants with significant vascular disease, stroke or TIA within 3 months prior to informed consent; co-existing cardiac disease including nonsinus rhythm, left bundle branch block, history of established epicardial CAD, previous revascularisation or previous myocardial infarction and severe hypertension greater than 180/110;
9. Participants with suboptimal echocardiographic image quality or ischaemia.
10. Known contraindications to eplerenone according to the local label;
11. Medical history of cancer (except for basal cell carcinoma) and/or treatment for cancer within the last 5 years;
12. Known blood dyscrasias or any disorders causing hemolysis or unstable red blood cell count (e.g. malaria, babesiosis, haemolytic anemia) due to the short lifespan of the RBC and its impact on HbA1c;
13.Current treatment with systemic steroids (orally taken or parenteral) at time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent or any other uncontrolled endocrine disorder except T1D;
14. Premenopausal women (last menstruation =1 year prior to informed consent) who:
- are nursing or pregnant or
- are of childbearing potential and are not practicing an acceptable method of birth control, or do not plan to continue using this method throughout the trial and do not agree to submit to periodic pregnancy testing during participation in the trial. Acceptable methods of birth control include tubal ligation, transdermal patch, intra uterine devices/systems (IUDs/IUSs), oral, implantable or injectable contraceptives, complete sexual abstinence (if acceptable by local health authorities), double barrier method and vasectomised partner
15. Alcohol or drug abuse within the 3 months prior to informed consent that would interfere with trial participation or any ongoing condition leading to a decreased compliance to trial procedures or trial drug intake, in the judgment of the investigators.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Change in composite outcome of ambulatory blood pressure, resting blood pressure, heart rate, pulse wave velocity and cardiac function and structure: left ventricular indices such as mass, mass index, ejection fraction, diastolic function, left atrial size and right ventricular function at 12 weeks after intervention commencement.[Assessed at baseline and at 12 weeks after intervention commencement.];Change in haemostatic functions: <br>-reduction in prothrombotic and haemostatic/inflammatory factors such as von Willebrand Factor (vWF) antigen, platelet/granulocyte aggregates, thromboxane B2, whole blood aggregometry, fibrinogen, CRP, IL6, Factor VIII:c, Overall Haemostatic Potential (OHP) and cortisol at 12 weeks after intervention commencement.[Assessed at baseline and at 12 weeks after intervention commencement.];Change in central macula thickness (CMT) as measured by Optical Coherence Tomography (OCT). [Assessed at baseline and at 12 weeks after intervention commencement.]

Secondary Outcome Measures

Name	Time	Method
Changes in metabolic variables: including glycaemic control, determined by glycosylated HbA1c, fasting plasma glucose, fasting insulin, number of patients taking insulin compared to baseline, insulin dose and other medications at 12 weeks after intervention commencement.[Assessed at baseline and at 12 weeks after intervention commencement.];Idenitification of disease biomarkers such as microRNA, fibrosis and oxidative stress biomarkers by collecting plasma from both the healthy volunteer group (control) and comparing microRNA, protein markers of fibrosis and oxidative stress between the 2 groups. [Assessed at baseline and at 12 weeks after intervention commencement.];Impact on the individual's quality of life as assessed by questionnaires - Quality of Life (QOL) and Pittsburgh Sleep Quality Index.<br> [Assessed at baseline and at 12 weeks after intervention commencement.]