Effects of Liraglutide in Young Adults With Type 2 DIAbetes (LYDIA)

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by University of Leicester
Sponsor:
Collaborators:
Novo Nordisk A/S
University Hospitals, Leicester
Information provided by (Responsible Party):
University of Leicester
ClinicalTrials.gov Identifier:
NCT02043054
First received: January 17, 2014
Last updated: February 25, 2014
Last verified: February 2014
  Purpose

There are recent advances in therapies for the treatment of Type 2 Diabetes Mellitus (T2DM) which include the GLP1 analogues and the DPP IV inhibitors. Both of these therapies target the incretin system using different methods to elevate/maintain circulating levels of GLP1 to subsequently achieve improved blood sugar control. Interestingly, GLP1 analogues have been reported not only to improve blood sugar control but to additionally induce weight-loss and emerging experimental evidence has shown it may have beneficial effects on the heart's structure and function. Due to the profile of this condition being a lot worse and younger patients having greater CVD risk, a therapy offering multiple positive effects, in particular the potential cardiometabolic effects, make this line of therapy attractive in this patient population.

The aim of this research is to investigate the cardiometabolic effects of Liraglutide (GLP1 analogue) compared to that of its clinically relevant comparator Sitagliptin (DPP IV inhibitor).


Condition Intervention Phase
Type 2 Diabetes Mellitus
Cardiovascular Disease
Drug: Liraglutide
Drug: Sitagliptin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Impact of Liraglutide on Cardiac Function and Structure in Young Adults With Type 2 Diabetes: an Open-label, Randomised Active-comparator Trial

Resource links provided by NLM:


Further study details as provided by University of Leicester:

Primary Outcome Measures:
  • Change in peak end diastolic strain rate [ Time Frame: Change from baseline peak end diastolic strain rate at 26 weeks ] [ Designated as safety issue: Yes ]
    It is now well recognised that diastolic dysfunction is the primary characteristic of heart disease in T2DM. Measured by gold-standard tagged cardiac MRI. MRI scans will be anonymised and sent to a stand-alone work station for independent analysis.


Secondary Outcome Measures:
  • Composite of standard biochemical variables [ Time Frame: Changes from baseline to 26 weeks ] [ Designated as safety issue: No ]

    (measured blinded to treatment allocation by UHL Pathology labs measured at baseline, 12 weeks to 26 weeks)

    • HbA1c
    • Liver Function Tests
    • Lipid profile including total-, LDL- and HDL-cholesterol and triglycerides
    • Thyroid function tests
    • Complete Blood Count (Hematocrit)
    • Vitamin D

  • Composite chronic low-grade inflammation and adiposity [ Time Frame: Changes from baseline to 26 weeks ] [ Designated as safety issue: No ]

    (measured blinded to treatment allocation in specialist laboratories at baseline, 12 weeks and 26 weeks):

    • Interleukin-6
    • C-reactive protein
    • Leptin
    • Adiponectin

  • Composite Endothelial Function [ Time Frame: Changes from Baseline to 26 weeks ] [ Designated as safety issue: No ]

    Assessed using biological markers. A blood sample will be taken at baseline and 26 weeks and the serum analysed using MSD multiplex panels for the following markers of vascular injury:

    • Panel 1) sICAM-3, e-Selectin, Thrombomodulin,
    • Panel 2) CRP, sICAM, sVCAM, SAA

    Evaluation of endothelial progenitor cells, stromal derived factor (SDF-1 and GLP-1) and associated biomarkers in a sub-set of participants.


  • Composite Standard Anthropometric variables [ Time Frame: Changes from baseline to 26 weeks ] [ Designated as safety issue: No ]

    Measures taken at baseline, 12 and 26 weeks

    • BMI
    • Weight
    • Percentage body fat
    • Waist and hip circumferences
    • Systolic and Diastolic Blood pressure (average of 3 measures taken 5 minutes apart)
    • Heart rate (after resting seated for at least 5 minutes

  • MRI defined adiposity [ Time Frame: Changes from baseline to 26 weeks ] [ Designated as safety issue: No ]
    • Subcutaneous, visceral and hepatic adiposity volumes (measured through semi-automated analysis)

  • Composite Lifestyle variables [ Time Frame: Changes from baseline to 26 weeks ] [ Designated as safety issue: No ]

    Measured at baseline, 12 and 26 weeks

    • Cardio-respiratory fitness (graded VO2 max test)
    • Total physical activity and time in sedentary behaviour, light-, moderate-, and vigorous-intensity physical activity (ActiGraph GT3X accelerometer worn around the waist during waking hours for 7 consecutive days)
    • Sitting time (thigh mounted ActivPal inclinometer worn for 7 consecutive days)

  • Composite Quality of Life and Depression [ Time Frame: Changes from baseline to 26 weeks ] [ Designated as safety issue: No ]

    Measured at baseline, 12 and 26 weeks

    • EQ5D
    • Hospital anxiety and depression score

  • Composite treatment and satisfaction [ Time Frame: Changes from Baseline to 26 weeks ] [ Designated as safety issue: No ]

    Measured at baseline, 12 and 26 weeks

    • DTSQ


  • Compposite Medication Usage [ Time Frame: Changes from Baseline to 26 weeks ] [ Designated as safety issue: No ]
    • Changes to SU, lipid lowering and anti-hypertensive medication usage recorded at baseline, 12 and 26 weeks

  • Composite Hypoglycemic Episodes [ Time Frame: Changes from baseline to 26 weeks ] [ Designated as safety issue: Yes ]
    Self-reported in a standardized hypoglycemia diary.

  • Composite Outcomes [ Time Frame: Post-26 week analysis ] [ Designated as safety issue: No ]
    1. HbA1c <7.0%, no weight gain and no minor or major hypoglycemia
    2. HbA1c <7.0% and no weight gain
    3. HbA1c <7%, SBP <130 mmHg, and no weight gain
    4. HbA1c <7% and SBP <130 mmHg
    5. Adverse events (see Section 16 for criteria)

  • Composite MRI Outcomes [ Time Frame: Change from baseline cardiac measures at 26 weeks ] [ Designated as safety issue: Yes ]

    Other cardiac measures of function and structure will include:

    • Peak Systolic Strain
    • Left Ventricular Ejection Fraction
    • Stroke volume
    • LV end-diastolic volume
    • LV end-systolic volume
    • LV end-diastolic mass
    • Left Ventricular End Diastolic Mass/volume ratio
    • Pre-and post contrast T1 mapping to calculate volume of distribution, a marker of diffuse cardiac fibrosis
    • Myocardial Perfusion Reserve ( a measure of microvascular function)

  • Composite 7 point glucose profile [ Time Frame: Chanegs from baseline to 26 weeks ] [ Designated as safety issue: No ]
    Participants will be requested to provide a 7-point glucose profile measured at treatment initiation,12 and 26 week follow-up.


Estimated Enrollment: 90
Study Start Date: January 2014
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Liraglutide
Liraglutide doses will be self-administered by the participant through daily subcutaneous injections. Liraglutide doses will be initiated at 0.6 mg and then increased to 1.2 mg in week two and 1.8mg in week three. The dose will then be maintained at 1.8 mg. Where 1.8 mg doses are not tolerated by the patient, the dose will be lowered to the maximum tolerated dose at the investigators discretion.
Drug: Liraglutide

Liraglutide (Victoza®, Novo Nordisk) is a stable analogue of the natural hormone glucagon-like peptide-1 (GLP-1). Liraglutide is licensed for use within the United Kingdom and recommended by NICE in combination with metformin, and/or sulphonylurea and/or thiazolidinedione if the following conditions are satisfied.

  • BMI ≥ 35 kg/m2 in those of European descent (with appropriate adjustment for other ethnic groups) and specific psychological or medical problems associated with high body weight, or
  • BMI < 35 kg/m2, and therapy with insulin would have significant occupational implications or weight loss would benefit other significant obesity-related comorbidities.
Other Name: Victoza
Active Comparator: Sitagliptin
Sitagliptin doses will be self-administered by the participant orally at 100mg/day throughout the 26 week period of the study. Sitagliptin is licensed to be used either alone or in combination with other oral antihyperglycemic agents (such as metformin or a sulphonylurea)
Drug: Sitagliptin
Sitagliptin (Januvia®, Merck & Co) is an enzyme-inhibiting drug used to inhibit the natural enzyme dipeptidyl peptidase-4 (DPP-4). It is an oral antihyperglycaemic agent used in the treatment of T2DM. Sitagliptin is licensed to be used either alone or in combination with other oral antihyperglycemic agents (such as metformin or a sulphonylurea) and is recommended by NICE as a second line therapy.
Other Name: Januvia

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Capacity to provide informed consent before any trial-related activities
  • Individuals aged 18 - 50 years inclusive
  • Established T2DM
  • BMI ≥ 30 kg/m2 (≥27 kg/m2 for South Asians or other BME populations)
  • On mono or combination oral OAD therapy (sulphonylurea and/or metformin) for ≥ 3months
  • No prescribed thiazolidinediones within the last 3 months
  • An HbA1c value of greater than or equal to 6.5% and less than 10%

Exclusion Criteria:

  • < 18 years old
  • Absolute contraindications to MRI
  • Type 1 diabetes (identified through C-peptide analysis)
  • Females of child bearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods
  • Suffer from terminal illness
  • Have impaired renal function (eGFR < 30 ml/min/1.73m2) )
  • Impaired liver function (ALAT≥2.5 times upper limit of normal)
  • Known to be Hepatitis B antigen or Hepatitis C antibody positive
  • Clinically significant active cardiovascular disease including history of myocardial infarction within the past 6 months and/or heart failure (NYHA class III and IV) at the discretion of the investigator
  • Recurrent major hypoglycaemia as judged by the investigator
  • Known or suspected allergy to the trial products
  • Known or suspected thyroid disease
  • Receipt of any investigational drug within four weeks prior to this trial
  • Have severe and enduring mental health problems
  • Are not primarily responsible for their own care
  • Are receiving insulin therapy
  • Have taken a thiazolidinedione within the last 3 months
  • Any contraindication to Sitagliptin or Liraglutide
  • Have severe irritable bowel disorder
  • Have pancreatitis or a previous history of pancreatitis
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02043054

Contacts
Contact: Sarah L Edwards, Dr 0116 258 8637 ext 8637 sarah.edwards@le.ac.uk
Contact: Helen Dallosso, Dr 0116 258 4738 ext 4738 helen.dallosso@uhl-tr.nhs.uk

Locations
United Kingdom
University Hospitals of Leicester NHS Trust, Diabetes Research Centre Recruiting
Leicester, Leicestershire, United Kingdom, LE5 4PW
Contact: Sarah Edwards, Dr    0116 258 8637 ext 8637    sarah.edwards@le.ac.uk   
Contact: Helen Dallosso, Dr    0116 258 4738 ext 4738    helen.dallosso@uhl-tr.nhs.uk   
Principal Investigator: Melanie Davies, Prof         
Sub-Investigator: Thomas Yates, Dr         
Sub-Investigator: Kamlesh Khunti, Prof         
Sub-Investigator: Gerry McCann, Dr         
Sub-Investigator: Laura Gray, Dr         
Sub-Investigator: David Webb, Dr         
Sub-Investigator: Zin Zin Htike, Dr         
Sponsors and Collaborators
University of Leicester
Novo Nordisk A/S
University Hospitals, Leicester
Investigators
Principal Investigator: Melanie Davies, Prof University of Leicester
  More Information

No publications provided

Responsible Party: University of Leicester
ClinicalTrials.gov Identifier: NCT02043054     History of Changes
Other Study ID Numbers: 0398 / 201200242278, 2012-002422-78, U1111-1131-8802
Study First Received: January 17, 2014
Last Updated: February 25, 2014
Health Authority: England: Medicines and Healthcare Products Regulatory Agency (MHRA)

Keywords provided by University of Leicester:
Type 2 Diabetes Mellitus (T2DM)
Young Adults
Cardiovascular Disease (CVD)
GLP1 Analogue
DPP IV Inhibitor
Obesity
Cardiometabolic Effects
Cardiac MRI

Additional relevant MeSH terms:
Cardiovascular Diseases
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Liraglutide
Sitagliptin
Hypoglycemic Agents
Glucagon-Like Peptide 1
Physiological Effects of Drugs
Pharmacologic Actions
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014