Does Dapaglifozin Regress Left Ventricular Hypertrophy In Patients With Type 2 Diabetes?

Phase 1

• Conditions: Type 2 diabetes and left ventricular hypertrophy; MedDRA version: 20.0Level: PTClassification code 10061024Term: Cardiac disorderSystem Organ Class: 10007541 - Cardiac disorders; MedDRA version: 20.0Level: PTClassification code 10067585Term: Type 2 diabetes mellitusSystem Organ Class: 10027433 - Metabolism and nutrition disorders; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2016-000715-33-GB
• Lead Sponsor: niversity of Dundee & NHS Tayside

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Completion: 2019-03-15
• Study Start: 2019-05-01
• Last Update Posted: 27 July 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 66

Inclusion Criteria

1.Provision of informed consent before any trial specific procedures.
2.Diagnosed with type 2 diabetes mellitus based on the current American Diabetes Association guidelines.
3.Aged >18 and <80 years
4.Body Mass Index =23
5.HbA1c 48-85mmol/mol (last known result within in the previous 6 months)
6.BP <145/90mmHg
7.Echocardiographic LV hypertrophy (defined as either an LV mass index of >115g/m2 for men and >95g/m2 for women indexed to body surface area or > 44g/m2.7 or 48g/m2.7 when indexed to height) within the previous 6 months.
8.Women of childbearing potential must agree to take precautions to avoid pregnancy throughout the trial and for 4 weeks after intake of the last dose.

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 44

Exclusion Criteria

1.Any condition that in the opinion of the investigator may render the participant unable to complete the trial including non CV disease (e.g. active malignancy).
2.Participants with type 1 diabetes mellitus
3.Diagnosis of clinical heart failure
4.History of humun immunodeficiency virus
5.LV systolic dysfunction (LVEF <45%) (last known result within in the previous 6 months)
6.eGFR <45ml/min (last known result within in the previous month)
7.Known liver function tests >3 times upper limit of normal (based on last measures and documented laboratory measurement in the previous 6 months)
8.Body weight >150Kg (unable to fit into a MRI scanner)
9.Contraindications to MRI (e.g. claustrophobia, metal implants, penetrative eye injury or exposure to metal fragments in eye requiring medical attention)
10.Past or current treatment with any SGLT2 inhibitor
11.Allergy to any SGLT2 inhibitor or lactose or galactose intolerance
12.Current treatment with loop diuretic
13.Currently receiving long term (>30 consecutive days) treatment with an oral steroid
14.Pregnant or breast feeding participants
15.Involvement in the planning and/or conduct of the trial (applies to Astra Zeneca or representative staff and/or staff at the trial site).
16.Participation in another interventional study (other than observational trials and registries) within 30 days before visit 1.
17.Individuals considered at risk for poor protocol or medication compliance.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To see if Dapagliflozin reduces left ventricular size more than placebo in participants with type 2 diabetes and left ventricular hypertrophy ;Secondary Objective: To confirm expected effect of dapagliflozin on blood pressure (reduce blood pressure)<br>To assess the effect of dapagliflozin on left ventricular diastolic function and global longitudinal strain <br>To confirm expected effect of dapagliflozin on body weight (reduce weight)<br>To assess the effect of dapagliflozin on visceral fat mass.<br>To assess the effects of dapagliflozin on blood biomarkers.<br>To assess the tolerability of dapagliflozin in this patient group;Primary end point(s): LV Mass by Cardiac MRI;Timepoint(s) of evaluation of this end point: 0 & 52 weeks

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1) To confirm expected effect of dapagliflozin on 24 hour BP <br>2) To confirm expected effect of dapagliflozin on Office BP<br>3) To confirm expected effect of dapagliflozin on body weight<br>4) To assess the effect of dapagliflozin on visceral fat mass.<br>5) To assess the effects of dapagliflozin on biomarkers.<br>6) To assess the tolerability of dapagliflozin in this patient group<br>;Timepoint(s) of evaluation of this end point: 1) 0 & 52 weeks<br>2) 0, 4, 17, 34 & 52 weeks<br>3) 0, 4, 17, 34 & 52 weeks<br>4) 0 & 52 weeks<br>5) 0, 4, 17, 34 & 52 weeks<br>6) 0, 4, 17, 34 & 52 weeks