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

Primary Purpose

Type 2 Diabetes, Cardiovascular Diseases

Status
Withdrawn
Phase
Phase 3
Locations
Germany
Study Type
Interventional
Intervention
Liraglutide Pen Injector [Victoza]
Placebo
Sponsored by
RWTH Aachen University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Type 2 Diabetes focused on measuring Liraglutide, Type 2 Diabetes, High Cardiovascular Risk, Myocardial Infarction, Metabolic Profile

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Department of Internal Medicine I, University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Liraglutide

Placebo

Arm Description

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.

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

Outcomes

Primary Outcome Measures

Changes in the metabolomics profile (fold changes) between Liraglutide treatment group and placebo group after 1 and 3 months
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

change in left ventricular diastolic function
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
change in left ventricular diastolic function
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
change in left ventricular systolic function
change in left ventricular systolic function by ejection fraction (EF) by echocardiography
Changes in systolic and diastolic blood pressure (mmHg)
Changes in systolic and diastolic blood pressure (mmHg) between Liraglutide treatment group and placebo group after 1 and 3 months.
body weight
Changes in NT-proBNP serum levels (pg/ml)
Changes in NT-proBNP serum levels (pg/ml) between Liraglutide treatment group versus placebo group after 1 and 3 months.
Differences of the serum lipid profile between Liraglutide treatment group and placebo group
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
changes of serum levels of glucose, HbA1c, glucagon, insulin, C-Peptide, β-Hydroxybutyrate between Liraglutide treatment group and placebo group
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
Heart rate variability
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).
Resting energy expenditure
Resting energy expenditure measured by indirect calorimetry [CardioCoach CO2]
Respiratory Exchange Ratio
Respiratory Exchange Ratio measured by indirect calorimetry [CardioCoach CO2]
Differences in gut microbiome composition measured by 16S rRNA targeted gene sequencing of feces between Liraglutide treatment group and placebo group
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).
Albumin excretion
Albumin excretion by 24 h urine collection
changes in inflammasome analyses
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
Differences in circulation inflammatory cell composition by flow cytometry analyses (FACS) between Liraglutide treatment group and placebo group
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).

Full Information

First Posted
July 18, 2019
Last Updated
March 9, 2021
Sponsor
RWTH Aachen University
Collaborators
Novo Nordisk A/S
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1. Study Identification

Unique Protocol Identification Number
NCT04057261
Brief Title
Effect of Liraglutide on the Metabolic Profile in Patients With Type 2 Diabetes and Cardiovascular Disease
Acronym
Lirabolic
Official Title
Effect of Liraglutide on the Metabolic Profile in Patients With Type 2 Diabetes and Cardiovascular Disease
Study Type
Interventional

2. Study Status

Record Verification Date
March 2021
Overall Recruitment Status
Withdrawn
Why Stopped
A study start is currently not foreseeable for organizational reasons. Due to the delays, research has also been focused on new compounds, which has reduced the interest in the potential results of the above-mentioned clinical trial.
Study Start Date
November 2020 (Anticipated)
Primary Completion Date
August 2022 (Anticipated)
Study Completion Date
November 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
RWTH Aachen University
Collaborators
Novo Nordisk A/S

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 2 Diabetes, Cardiovascular Diseases
Keywords
Liraglutide, Type 2 Diabetes, High Cardiovascular Risk, Myocardial Infarction, Metabolic Profile

7. Study Design

Primary Purpose
Other
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Single center, prospective, placebo-controlled, double-blind, randomized, 2 arm parallel, interventional, exploratory pilot study
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Liraglutide
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Matching Placebo once daily, subcutaneous injection via pre-filled pen.
Intervention Type
Drug
Intervention Name(s)
Liraglutide Pen Injector [Victoza]
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching Placebo once daily, subcutaneous injection via pre-filled pen.
Primary Outcome Measure Information:
Title
Changes in the metabolomics profile (fold changes) between Liraglutide treatment group and placebo group after 1 and 3 months
Description
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.
Time Frame
3 month
Secondary Outcome Measure Information:
Title
change in left ventricular diastolic function
Description
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
Time Frame
3 month
Title
change in left ventricular diastolic function
Description
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
Time Frame
3 month
Title
change in left ventricular systolic function
Description
change in left ventricular systolic function by ejection fraction (EF) by echocardiography
Time Frame
3 month
Title
Changes in systolic and diastolic blood pressure (mmHg)
Description
Changes in systolic and diastolic blood pressure (mmHg) between Liraglutide treatment group and placebo group after 1 and 3 months.
Time Frame
3 month
Title
body weight
Time Frame
3 month
Title
Changes in NT-proBNP serum levels (pg/ml)
Description
Changes in NT-proBNP serum levels (pg/ml) between Liraglutide treatment group versus placebo group after 1 and 3 months.
Time Frame
3 month
Title
Differences of the serum lipid profile between Liraglutide treatment group and placebo group
Description
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
Time Frame
3 month
Title
changes of serum levels of glucose, HbA1c, glucagon, insulin, C-Peptide, β-Hydroxybutyrate between Liraglutide treatment group and placebo group
Description
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
Time Frame
3 month
Title
Heart rate variability
Description
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).
Time Frame
3 month
Title
Resting energy expenditure
Description
Resting energy expenditure measured by indirect calorimetry [CardioCoach CO2]
Time Frame
3 month
Title
Respiratory Exchange Ratio
Description
Respiratory Exchange Ratio measured by indirect calorimetry [CardioCoach CO2]
Time Frame
3 month
Title
Differences in gut microbiome composition measured by 16S rRNA targeted gene sequencing of feces between Liraglutide treatment group and placebo group
Description
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).
Time Frame
3 month
Title
Albumin excretion
Description
Albumin excretion by 24 h urine collection
Time Frame
3 month
Title
changes in inflammasome analyses
Description
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
Time Frame
3 month
Title
Differences in circulation inflammatory cell composition by flow cytometry analyses (FACS) between Liraglutide treatment group and placebo group
Description
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).
Time Frame
3 month

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Type 2 diabetes Serum levels of HbA1c ≥ 7,0% Age ≥ 18 years 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) Written informed consent prior to study participation Exclusion Criteria: Type 1 diabetes Treatment with GLP-1 receptor agonists or DPP-4 inhibitors within the last 4 weeks Patients with familiar or personal history of multiple endocrine neoplasia-type 2 or medullary C-cell cancer Renal impairment (eGFR < 30 mL/min) Occurrence of acute vascular events within 6 weeks before screening and randomization Known or suspected hypersensitivity to Liraglutide 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. Lactating females 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. The subject received an investigational drug within 30 days prior to inclusion into this study. 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. The subject is unwilling or unable to follow the procedures outlined in the protocol. The subject is mentally or legally incapacitated.
Facility Information:
Facility Name
Department of Internal Medicine I, University Hospital
City
Aachen
ZIP/Postal Code
52074
Country
Germany

12. IPD Sharing Statement

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

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