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Effect of Liraglutide on the Metabolic Profile in Patients With Type 2 Diabetes and Cardiovascular Disease (Lirabolic)

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ClinicalTrials.gov Identifier: NCT04057261
Recruitment Status : Not yet recruiting
First Posted : August 15, 2019
Last Update Posted : September 11, 2019
Sponsor:
Collaborator:
Novo Nordisk A/S
Information provided by (Responsible Party):
RWTH Aachen University

Brief Summary:
In an unbiased metabolomics approach with subsequent pathway analyses, the current study seeks to examine the effect of Liraglutide treatment on the metabolic signature in treated patients as well as the effect of Liraglutide on various echocardiographic parameters of cardiac function and rhythm profile, thus paving the way for future research to explain the effects of Liraglutide on cardiovascular mortality and overall mortality in treated patients.

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Cardiovascular Diseases Drug: Liraglutide Pen Injector [Victoza] Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Single center, prospective, placebo-controlled, double-blind, randomized, 2 arm parallel, interventional, exploratory pilot study
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Other
Official Title: Effect of Liraglutide on the Metabolic Profile in Patients With Type 2 Diabetes and Cardiovascular Disease
Estimated Study Start Date : November 2019
Estimated Primary Completion Date : August 2021
Estimated Study Completion Date : November 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Liraglutide

Arm Intervention/treatment
Active Comparator: Liraglutide
Increasing dose of Liraglutide: 0.6 mg/d for the first week, 1.2 mg/d for the second week aiming for a maximum of 1.8 mg/d beginning with the third week (or highest tolerated dose).Subcutaneous injection once daily via pre-filled pen.
Drug: Liraglutide Pen Injector [Victoza]
Increasing dose of Liraglutide: 0.6 mg/d for the first week, 1.2 mg/d for the second week aiming for a maximum of 1.8 mg/d beginning with the third week (or highest tolerated dose).Subcutaneous injection once daily via pre-filled pen

Placebo Comparator: Placebo
Matching Placebo once daily, subcutaneous injection via pre-filled pen.
Drug: Placebo
Matching Placebo once daily, subcutaneous injection via pre-filled pen.




Primary Outcome Measures :
  1. Changes in the metabolomics profile (fold changes) between Liraglutide treatment group and placebo group after 1 and 3 months [ Time Frame: 3 month ]
    Changes in the metabolomics profile (fold changes) between Liraglutide treatment group and placebo group after 1 and 3 months measured by a platform including 2 separate reverse phase (RP)/UPLC-MS/MS with positive ion mode electrospray ionization (ESI), (RP)/UPLC-MS/MS with negative ESI, and (HILIC)/UPLC-MS/MS with negative ESI.


Secondary Outcome Measures :
  1. change in left ventricular diastolic function [ Time Frame: 3 month ]
    change in left ventricular diastolic function between baseline and after 12 weeks as determined by 2D and 3D parameter global Strain Rate E by echocardiography

  2. change in left ventricular diastolic function [ Time Frame: 3 month ]
    change in left ventricular diastolic function between baseline and after 12 weeks as determined by standardized parameter E/é and left atrial (LA) volume by echocardiography

  3. change in left ventricular systolic function [ Time Frame: 3 month ]
    change in left ventricular systolic function by ejection fraction (EF) by echocardiography

  4. Changes in systolic and diastolic blood pressure (mmHg) [ Time Frame: 3 month ]
    Changes in systolic and diastolic blood pressure (mmHg) between Liraglutide treatment group and placebo group after 1 and 3 months.

  5. body weight [ Time Frame: 3 month ]
  6. Changes in NT-proBNP serum levels (pg/ml) [ Time Frame: 3 month ]
    Changes in NT-proBNP serum levels (pg/ml) between Liraglutide treatment group versus placebo group after 1 and 3 months.

  7. Differences of the serum lipid profile between Liraglutide treatment group and placebo group [ Time Frame: 3 month ]
    Differences of the serum lipid profile including serum levels of triglycerides (mg/dl), total cholesterol (mg/dl), low-density lipoprotein cholesterol (mg/dl) and high-density lipoprotein cholesterol (mg/dl)between Liraglutide treatment group and placebo group after 1 and 3 months

  8. changes of serum levels of glucose, HbA1c, glucagon, insulin, C-Peptide, β-Hydroxybutyrate between Liraglutide treatment group and placebo group [ Time Frame: 3 month ]
    Changes in serum levels of glucose (mg/dl), HbA1c (%), glucagon (pg/ml), insulin (ng/ml), C-Peptide (ng/ml), β-Hydroxybutyrate (mmol/l) between Liraglutide treatment group and placebo group after 1 and 3 months

  9. Heart rate variability [ Time Frame: 3 month ]
    Differences in heart rate variability measured by 24 hour ECG between Liraglutide treatment group and placebo group after 3 month including the following parameters: mean heart rate (bpm), maximum/minimum heart rate (bpm) and long-term variation of RR intervals (defined as standard deviation over 24 hours of per-minute means of RR intervals).

  10. Resting energy expenditure [ Time Frame: 3 month ]
    Resting energy expenditure measured by indirect calorimetry [CardioCoach CO2]

  11. Respiratory Exchange Ratio [ Time Frame: 3 month ]
    Respiratory Exchange Ratio measured by indirect calorimetry [CardioCoach CO2]

  12. Differences in gut microbiome composition measured by 16S rRNA targeted gene sequencing of feces between Liraglutide treatment group and placebo group [ Time Frame: 3 month ]
    Differences in gut microbiome composition measured by 16S rRNA targeted gene sequencing of feces between Liraglutide treatment group and placebo group after 1 and 3 month including the following parameters: alpha diversity (reported as Shannon diversity index) and differences in bacterial composition at different taxonomic levels including genus, family and class of bacteria (reported as relative abundance).

  13. Albumin excretion [ Time Frame: 3 month ]
    Albumin excretion by 24 h urine collection

  14. changes in inflammasome analyses [ Time Frame: 3 month ]
    Differences in serum levels of inflammatory cytokines including C-reactive protein (mg/ml), Interleukin 6 (pg/ml), Interleukin 1 beta (pg/ml) and tumor necrosis factor alpha (pg/ml) between Liraglutide treatment group and placebo group after 1 and 3 month

  15. Differences in circulation inflammatory cell composition by flow cytometry analyses (FACS) between Liraglutide treatment group and placebo group [ Time Frame: 3 month ]
    Differences in circulation inflammatory cell composition by flow cytometry analyses (FACS) between Liraglutide treatment group and placebo group after 1 and 3 month including the following parameters: Numbers of T-cells including T-cell subsets and monocytes including monocyte subsets. Numbers will be reported as percentage of parent, i.e. total pool of CD45+ immune cells).



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

Inclusion Criteria:

  1. Type 2 diabetes
  2. Serum levels of HbA1c ≥ 7,0%
  3. Age ≥ 18 years
  4. Patients with existing cardiovascular disease: coronary heart disease, cerebrovascular disease, peripheral vascular disease, chronic kidney disease of stage III or chronic heart failure of NYHA II or III)
  5. Written informed consent prior to study participation

Exclusion Criteria:

  1. Type 1 diabetes
  2. Treatment with GLP-1 receptor agonists or DPP-4 inhibitors within the last 4 weeks
  3. Patients with familiar or personal history of multiple endocrine neoplasia-type 2 or medullary C-cell cancer
  4. Renal impairment (eGFR < 30 mL/min)
  5. Occurrence of acute vascular events within 6 weeks before screening and randomization
  6. Known or suspected hypersensitivity to Liraglutide
  7. Pregnant females as determined by positive (serum or urine) hCG test at Screening or prior to dosing. Participants of child-bearing age should use adequate contraception as defined in the study protocol.
  8. Lactating females
  9. The subject has a history of any other illness, which, in the opinion of the Investigator, might pose an unacceptable risk by administering study medication.
  10. The subject received an investigational drug within 30 days prior to inclusion into this study.
  11. The subject has any current or past medical condition and/or required medication to treat a condition that could affect the evaluation of the study.
  12. The subject is unwilling or unable to follow the procedures outlined in the protocol.
  13. The subject is mentally or legally incapacitated.

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): NCT04057261


Contacts
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Contact: Nikolaus Marx, Prof. Dr. med. +49 241 80 ext 89301 nmarx@ukaachen.de
Contact: Michael Lehrke, Dr. med. +49 241 80 ext 88763 mlehrke@ukaachen.de

Locations
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Germany
Department of Internal Medicine I, University Hospital
Aachen, Germany, 52074
Sponsors and Collaborators
RWTH Aachen University
Novo Nordisk A/S

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Responsible Party: RWTH Aachen University
ClinicalTrials.gov Identifier: NCT04057261     History of Changes
Other Study ID Numbers: 17-162
First Posted: August 15, 2019    Key Record Dates
Last Update Posted: September 11, 2019
Last Verified: September 2019

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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 RWTH Aachen University:
Liraglutide
Type 2 Diabetes
High Cardiovascular Risk
Myocardial Infarction
Metabolic Profile
Additional relevant MeSH terms:
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Liraglutide
Diabetes Mellitus
Diabetes Mellitus, Type 2
Cardiovascular Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists