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

NCT02956811 | Completed Phase 4

• 2 other identifiers: 2015DM072016-000715-33
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

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.

Conditions

Type 2 Diabetes; Left Ventricular Hypertrophy

Keywords

Type 2 Diabetes; Left Ventricular Hypertrophy; Dapagliflozin

Outcome Measures

Primary Outcomes (1)

• Change in left ventricular (LV) Mass by Cardiac MRI at 52 weeks

  To see if Dapagliflozin reduces LV mass more than placebo in participants with type 2 diabetes and LV hypertrophy

  Baseline and 52 weeks

Secondary Outcomes (13)

• Change in 24 hour blood pressure (BP) recording at 52 weeks

  Baseline and 52 weeks

• Change in Office blood pressure (BP) at 4, 17, 34 and 52 weeks

  Baseline, 4, 17, 34 and 52 weeks

• Change in Body mass index at 4, 17, 34 and 52 weeks

  Baseline 4, 17, 34 and 52 weeks

• Change in waist/hip ratio at 4, 17, 34 and 52 weeks

  Baseline 4, 17, 34 and 52 weeks

• Change in waist circumference at 4, 17, 34 and 52 weeks

  Baseline 4, 17, 34 and 52 weeks

Study Arms (2)

Active

ACTIVE COMPARATOR

Dapagliflozin 10mg once daily for 12 months

Drug: Dapagliflozin

Placebo

PLACEBO COMPARATOR

Placebo 10mg once daily for 12 months

Drug: Placebo

Interventions

Dapagliflozin DRUG

SGLT2 inhibitor

Also known as: Forxiga

Active

Placebo DRUG

Matching Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of informed consent before any trial specific procedures.
• Diagnosed with type 2 diabetes mellitus based on the current American Diabetes Association guidelines.
• Aged \>18 and \<80 years
• Body Mass Index ≥23
• HbA1c 48-85mmol/mol (last known result within in the previous 6 months)
• 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.
• 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.

You may not qualify if:

• \. 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).
• Participants with type 1 diabetes mellitus
• Participants who have previously had an episode of diabetic ketoacidosis.
• Serum Potassium or Sodium results outwith the normal range
• Diagnosis of clinical heart failure
• History of human immunodeficiency virus
• LV systolic dysfunction (LVEF \<45%) (last known result within in the previous 6 months)
• eGFR \<45ml/min (last known result within in the previous month)
• Known liver function tests \>3 times upper limit of normal (based on last measures and documented laboratory measurement in the previous 6 months)
• Body weight \>150Kg (unable to fit into a MRI scanner)
• Contraindications to MRI (e.g. claustrophobia, metal implants, penetrative eye injury or exposure to metal fragments in eye requiring medical attention)
• Past or current treatment with any SGLT2 inhibitor
• Allergy to any SGLT2 inhibitor or lactose or galactose intolerance
• Current treatment with loop diuretic
• Currently receiving long term (\>30 consecutive days) treatment with an oral steroid

Sponsors & Collaborators

• University of Dundee: lead
• NHS Tayside: collaborator
• AstraZeneca: collaborator

Study Sites (1)

Ninewells Hospital

Dundee, United Kingdom

Location

Related Publications (3)

• Dihoum A, Brown AJ, McCrimmon RJ, Lang CC, Mordi IR. Dapagliflozin, inflammation and left ventricular remodelling in patients with type 2 diabetes and left ventricular hypertrophy. BMC Cardiovasc Disord. 2024 Jul 12;24(1):356. doi: 10.1186/s12872-024-04022-7.

  PMID: 38997620 DERIVED

• Brown AJM, Gandy S, McCrimmon R, Houston JG, Struthers AD, Lang CC. A randomized controlled trial of dapagliflozin on left ventricular hypertrophy in people with type two diabetes: the DAPA-LVH trial. Eur Heart J. 2020 Sep 21;41(36):3421-3432. doi: 10.1093/eurheartj/ehaa419.

  PMID: 32578850 DERIVED

• Brown AJM, Lang C, McCrimmon R, Struthers A. Does dapagliflozin regress left ventricular hypertrophy in patients with type 2 diabetes? A prospective, double-blind, randomised, placebo-controlled study. BMC Cardiovasc Disord. 2017 Aug 23;17(1):229. doi: 10.1186/s12872-017-0663-6.

  PMID: 28835229 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Hypertrophy, Left Ventricular

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Cardiomegaly; Heart Diseases; Cardiovascular Diseases; Hypertrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Study Officials

• Allan Struthers, MD, FRCP

  University of Dundee

  STUDY DIRECTOR

• Chim Lang, MD, FRCP

  University of Dundee

  PRINCIPAL INVESTIGATOR

• Graeme Houston, FRCR, MBBCh

  University of Dundee

  STUDY DIRECTOR

• Rory McCrimmon, MBChB, MRCP

  University of Dundee

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 7, 2016
• First Posted: November 7, 2016
• Study Start: February 14, 2017
• Primary Completion: March 14, 2019
• Study Completion: April 2, 2019
• Last Updated: July 9, 2019

Record last verified: 2019-07

Locations

GB (1)