Study to Assess the Efficacy of Liraglutide in Patients With Type 2 Diabetes Mellitus

February 9, 2021 updated by: Lecube, Albert, M.D.

Multicentre Randomized Double Blind, Crossover, Placebo Controlled Clinical Trial to Evaluate the Effect of Liraglutide on Lung Function in Patients With Type 2 Diabetes Mellitus (LIRALUNG Study)

Type 2 diabetes (T2DM) is related to reduced pulmonary function. As experimental studies with glucagon-like peptide 1 (GLP-1) have shown an increase in pulmonary surfactant secretion, and the GLP-1 receptor has been found in significant amounts in the lung, it could be hypothesized that the treatment with liraglutide (a GL-1 agonist) will improve this reduced pulmonary function

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

There is growing evidence to suggest an association between type 2 diabetes and impaired pulmonary function. In this regard, several cross-sectional studies have appeared showing decreased indices of forced expiration, lung volume and diffusion capacity as the main lung dysfunctions detected in type 2 diabetic populations. In fact, diabetes is frequently co-morbid with chronic obstructive pulmonary disease, and data from the Atherosclerosis Risk in Communities Study showed a faster pulmonary function decline in type 2 diabetic patients than in other participants. This is important because the reduction of FEV1 has been demonstrated an independent cause of mortality in diabetic patients.

Interestingly, lung function measures start to decrease several years before the diagnosis of diabetes. In this regard an investigation found that insulin resistance is an independent determinant of pulmonary function in non-diabetic morbidly obese women. In addition, the results suggest that the metabolic pathways related to insulin resistance are crucial in initiating lung abnormalities in type 2 diabetic patients.

The reasons for the association between respiratory disease and diabetes are unclear. However, the relationship between type 2 diabetes and muscle strength, the impairment in lung elastic properties, and the presence of a low-grade chronic inflammation state are involved. In supporting these findings, thickening of the alveolar epithelia and pulmonary capillary basal lamina, fibrosis, centrilobular emphysema, and pulmonary microangiopathy have been detected in autopsies of diabetic patients. In addition, defects in the bronchiolar surfactant layer, which is involved in maintaining airway stability and diameter, may also be considered a contributing factor to the impairment of airway calibre regulation in diabetic patients. When the alveolocapillary barrier is damaged, surfactant proteins leak into the bloodstream. A recent population-based random sample study has described how increased circulating levels of surfactant protein A, the major surfactant-associated protein, were associated with altered glucose tolerance and insulin resistance. Therefore, surfactant defects in diabetic individuals may also lead to an increase in airway resistance and to a reduction in ventilatory patterns as observed in our studies. In addition, as experimental studies have shown that glucagon-like peptide 1 plays a role in the stimulation of surfactant production, its underlying deficit in type 2 diabetes could also enhance the airway resistance observed in these patients. However, the beneficial effects on pulmonary function using incretin-based therapies remain to be elucidated.

Clinical trial study hypothesis is that treatment with an incretin mimetic such as liraglutide may ameliorate lung function parameters in type 2 diabetics patients, independently of weight reduction. This hypothesis is based on the following factors:

  1. - There is growing evidence to suggest an association between type 2 diabetes and impaired pulmonary function.
  2. - In patients with type 2 diabetes, the incretin effect is severely reduced or absent, contributing to the reduced lung function parameters observed in type 2 diabetic patients.
  3. - GLP-1 stimulates surfactant production in "in vitro" studies and, in consequence, the increase in surfactant production induced by liraglutide could be the main factor involved in the respiratory improvement.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
76

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Barcelona, Spain, 08035
        • Hospital Universitari Vall d´Hebron
      • Lleida, Spain, 25198
        • Hospital Universitari Arnau de Vilanova de Lleida
      • Málaga, Spain, 29010
        • Hospital Universitario Virgen de la Victoria
      • Sevilla, Spain, 41013
        • Hospital Universitario Virgen Del Rocio
    • Barcelona
      • Badalona, Barcelona, Spain, 08916
        • Hospital Universitari Germans Trias i Pujol
    • Navarra
      • Pamplona, Navarra, Spain, 31008
        • Clinica Universidad de Navarra

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

40 years to 65 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Signed informed consent.
  • Subjects between 40 and 65 years old. Diagnosis of type 2 diabetes mellitus with more than 5 years of evolution of disease.
  • Metformin (alone or in combination with sulfonylurea and / or insulin and / or thiazolidinediones) at a stable dose for at least the past 3 months.
  • HbA1c ≥ 7,0 y ≤ 9,0 %.
  • BMI between 30 and 40 kg / m2.
  • No pulmonary disease (COPD, asthma, fibrosis, etc) known.
  • Baseline FEV1 decline of equal or greater than 10% in the percentage of the theoretical value.
  • Chest radiography without significant changes in the lung parenchyma

Exclusion Criteria:

  • Type 1 diabetes mellitus
  • Treatment with inhibitors of dipeptidyl peptidase 4 glitazones and / or
  • SGLT2 inhibitors.
  • Active and former smokers for less than five years ago smoking.
  • Chronic obstructive pulmonary disease.
  • Respiratory sleep disorders that require treatment with continuous positive pressure in the airway.
  • Asthma treatment with bronchodilators.
  • Previous bariatric surgery.
  • Cardiovascular disease, heart failure and / or stroke.
  • Pathology of the chest wall.
  • Serum creatinine> 1.7 mg / dl.
  • Abnormal results in liver function test (Alanine transaminase/ Aspartate Aminotransferase greater than twice the upper limit of normal).
  • History of acute or chronic pancreatitis.
  • Personal or family history of medullary thyroid cancer or Multiple
  • Endocrine Neoplasia (MEN ) type 2.
  • Active neoplasms or neoplastic patients considered disease-free history from less than 5 years ago.
  • Women of childbearing age who are pregnant (positive pregnancy test within 14 days before the start of treatment) or intend to get pregnant.
  • Lactating women.
  • Women of childbearing potential not using adequate contraception (such as oral contraceptives, intrauterine device or barrier method of birth control along with spermicide or surgical sterilization) or unwilling to use during the study (as required by local laws or practices).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
OTHER: liraglutide
7-week subcutaneous liraglutide treatment once daily
Drug: liraglutide
7-week subcutaneous liraglutide once daily
OTHER: placebo
7-week subcutaneous placebo treatment once daily.
Drug: placebo
7-week subcutaneous placebo once daily

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Changes From Baseline on Measurements of Respiratory Function Defined by Forced Expiratory Volume in 1 Second (FEV1)
Time Frame: 7 weeks

Changes from baseline on measurements of respiratory function defined by forced expiratory volume in 1 second (FEV1).

Mean difference between 7 weeks after treatment visit and baseline visit is registered.
7 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Changes From Baseline on Measurements of Respiratory Function Defined by Forced Vital Capacity (FVC)
Time Frame: 7 weeks

Changes from baseline on measurements of respiratory function defined by forced vital capacity (FVC).

Mean difference between 7 weeks after treatment visit and baseline visit is registered.
7 weeks
Changes From Baseline in Serum Levels of Surfactant A and D Protein
Time Frame: 7 weeks
Changes from baseline in serum levels of surfactant A and D protein. Values for surfactant A or D protein after 7 treatment weeks (liraglutide or placebo) are registered.
7 weeks
Changes From Baseline on Measurements of Respiratory Function Defined by Maximum Mid-expiratory Flow (FEF25-75)
Time Frame: 7 weeks

Changes from baseline on measurements of respiratory function defined by Maximum mid-expiratory flow (FEF25-75).

Mean difference between 7 weeks after treatment visit and baseline visit is registered.
7 weeks
Changes From Baseline on Measurements of Respiratory Function Defined by Forced Expiratory Volume in 1 Second/Forced Vital Capacity (FEV1/FVC)
Time Frame: 7 weeks

Changes from baseline on measurements of respiratory function defined by forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC).

Mean difference between 7 weeks after treatment visit and baseline visit is registered.
7 weeks
Changes From Baseline on Measurements of Respiratory Function Defined by Residual Volume (RV)
Time Frame: 7 weeks
Changes from baseline on measurements of respiratory function defined by residual volume (RV).
7 weeks
Changes From Baseline on Measurements of Respiratory Function Defined by Total Lung Capacity (TLC)
Time Frame: 7 weeks
Changes from baseline on measurements of respiratory function defined by Total lung capacity (TLC).
7 weeks
Changes From Baseline on Measurements of Respiratory Function Defined by Residual Functional Capacity (RFC)
Time Frame: 7 weeks

Changes from baseline on measurements of respiratory function defined by Residual functional capacity (RFC) are registered.

However, this parameter was not determined in patients due to an error in the programm used.
7 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Lecube, Albert, M.D.

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Novo Nordisk A/S
Dynamic Solutions

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Albert Lecube, PhD, Hospital Universitari Arnau de Vilanova de Lleida

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 4, 2016

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 18, 2019

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 16, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 25, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 2, 2016

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 5, 2016

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 26, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 9, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • LIRALUNG

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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