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Does Dapagliflozin Regress Left Ventricular Hypertrophy In Patients With Type 2 Diabetes? (DAPA-LVH)

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ClinicalTrials.gov Identifier: NCT02956811
Recruitment Status : Completed
First Posted : November 7, 2016
Last Update Posted : July 9, 2019
Sponsor:
Collaborators:
NHS Tayside
AstraZeneca
Information provided by (Responsible Party):
University of Dundee

Brief Summary:

Left ventricular hypertrophy (LVH) is common in people with type 2 diabetes (70%) and is the strongest independent risk factor for cardiovascular events and all-cause mortality that there is. It is worse than triple vessel coronary disease. LVH often occurs in patients with "normal" blood pressures (BP). Apart from BP, the other three main factors causing LVH are insulin resistance, obesity and cardiac preload. Dapagliflozin reduces ALL four factors known to promote LVH i.e. Dapagliflozin reduces weight, glycaemia, preload and blood pressure and is therefore the ideal agent to reduce LVH since it uniquely attacks all four known mediators of LVH. This trial will investigate the ability of dapagliflozin to regress LVH in 64 participants with normotensive diabetes. This will be done by seeing if dapagliflozin reduces left ventricular mass as measured by cardiac magnetic resonance imaging (MRI). This trial may identify a novel way to reduce the strong independent risk factor of LVH which often persists despite optimum medical therapy in patients with diabetes. If dapagliflozin does reduce LVH, this would be a key sign of which subgroup of patients with diabetes (those with LVH) should be especially targeted with dapagliflozin.

64 participants with type 2 diabetes and LVH will be recruited through the Scottish Diabetes Research Network (SDRN), Scottish Primary Care Research Network (SPCRN) and other routes, in this single centre study. Participants will be randomised to receive either 10mg dapagliflozin or placebo daily for 12 months. Cardiac MRI will be performed at baseline and at 12 months, this will be assessed for the primary outcome of change in left ventricular mass. Secondary outcomes will examine change in 24 hour blood pressure and weight.


Condition or disease Intervention/treatment Phase
Type 2 Diabetes Left Ventricular Hypertrophy Drug: Dapagliflozin Drug: Placebo Phase 4

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 66 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: DAPA-LVH - Does Dapagliflozin Regress Left Ventricular Hypertrophy In Patients With Type 2 Diabetes?
Actual Study Start Date : February 14, 2017
Actual Primary Completion Date : March 14, 2019
Actual Study Completion Date : April 2, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Active
Dapagliflozin 10mg once daily for 12 months
Drug: Dapagliflozin
SGLT2 inhibitor
Other Name: Forxiga

Placebo Comparator: Placebo
Placebo 10mg once daily for 12 months
Drug: Placebo
Matching Placebo




Primary Outcome Measures :
  1. Change in left ventricular (LV) Mass by Cardiac MRI at 52 weeks [ Time Frame: Baseline and 52 weeks ]
    To see if Dapagliflozin reduces LV mass more than placebo in participants with type 2 diabetes and LV hypertrophy


Secondary Outcome Measures :
  1. Change in 24 hour blood pressure (BP) recording at 52 weeks [ Time Frame: Baseline and 52 weeks ]
    To confirm expected effect of dapagliflozin on BP

  2. Change in Office blood pressure (BP) at 4, 17, 34 and 52 weeks [ Time Frame: Baseline, 4, 17, 34 and 52 weeks ]
    To confirm expected effect of dapagliflozin on BP

  3. Change in Body mass index at 4, 17, 34 and 52 weeks [ Time Frame: Baseline 4, 17, 34 and 52 weeks ]
    To confirm expected effect of dapagliflozin on body mass index

  4. Change in waist/hip ratio at 4, 17, 34 and 52 weeks [ Time Frame: Baseline 4, 17, 34 and 52 weeks ]
    To confirm expected effect of dapagliflozin on waist/hip ratio

  5. Change in waist circumference at 4, 17, 34 and 52 weeks [ Time Frame: Baseline 4, 17, 34 and 52 weeks ]
    To confirm expected effect of dapagliflozin on waist circumference

  6. Change in visceral fat massed with Abdominal MRI at 52 weeks [ Time Frame: Baseline and 52 weeks ]
    To assess the effect of dapagliflozin on visceral fat mass.

  7. Change in HbA1c at 4, 17, 34 and 52 weeks [ Time Frame: Baseline, 4, 17, 34 and 52 weeks ]
    To assess the effects of dapagliflozin on HbA1c

  8. Number of patients with adverse events related to treatment [ Time Frame: 4, 17, 34 and 52 weeks ]
    Urinary symptoms and hypotensive symptoms will assess the tolerability of dapagliflozin in this patient group

  9. Number of participants with abnormal laboratory values [ Time Frame: 4, 17, 34 and 52 weeks ]
    Liver function tests will assess the tolerability of dapagliflozin in this patient group

  10. Change in Fasting Insulin Resistance Index (FIRI) at 4, 17, 34 and 52 weeks [ Time Frame: Baseline, 4, 17, 34 and 52 weeks ]
    To assess the effects of dapagliflozin on FIRI

  11. Change in B-type Natriuretic Peptide (BNP) at 4, 17, 34 and 52 weeks [ Time Frame: Baseline, 4, 17, 34 and 52 weeks ]
    To assess the effects of dapagliflozin on BNP

  12. Change in uric acid at 4, 17, 34 and 52 weeks [ Time Frame: Baseline, 4, 17, 34 and 52 weeks ]
    To assess the effects of dapagliflozin on uric acid

  13. Change in diastolic function and global longitudinal strain [ Time Frame: Baseline and 52 weeks ]
    To assess the effect of dapagliflozin on left ventricular diastolic function



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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. Blood pressure <145/90mmHg. Office BP at screening visit will be used however if this is above the inclusion criteria then the 24 hour or 16 hour recording at screening visit will be used to confirm that in the opinion of the PI the BP is adequately controlled.
  7. Echocardiographic left ventricular (LV) hypertrophy (defined as an LV mass index of >115g/m2 for men and >95g/m2 for women indexed to body surface area or >48g/m2.7 or >44g/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.

Exclusion Criteria:

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02956811


Locations
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United Kingdom
Ninewells Hospital
Dundee, United Kingdom
Sponsors and Collaborators
University of Dundee
NHS Tayside
AstraZeneca
Investigators
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Study Director: Allan Struthers, MD, FRCP University of Dundee
Principal Investigator: Chim Lang, MD, FRCP University of Dundee
Study Director: Graeme Houston, FRCR, MBBCh University of Dundee
Study Director: Rory McCrimmon, MBChB, MRCP University of Dundee

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: University of Dundee
ClinicalTrials.gov Identifier: NCT02956811     History of Changes
Other Study ID Numbers: 2015DM07
2016-000715-33 ( EudraCT Number )
First Posted: November 7, 2016    Key Record Dates
Last Update Posted: July 9, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Dundee:
Type 2 Diabetes
Left Ventricular Hypertrophy
Dapagliflozin
Additional relevant MeSH terms:
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Hypertrophy, Left Ventricular
Diabetes Mellitus
Diabetes Mellitus, Type 2
Hypertrophy
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Pathological Conditions, Anatomical
Cardiomegaly
Heart Diseases
Cardiovascular Diseases
2-(3-(4-ethoxybenzyl)-4-chlorophenyl)-6-hydroxymethyltetrahydro-2H-pyran-3,4,5-triol
Sodium-Glucose Transporter 2 Inhibitors
Molecular Mechanisms of Pharmacological Action
Hypoglycemic Agents
Physiological Effects of Drugs