Effect of Alirocumab on Postprandial Hyperlipemia in Patients With Type 2 Diabetes (EUTERPE)

September 26, 2022 updated by: Nantes University Hospital

Effect of Alirocumab on Postprandial Hyperlipemia in Patients With Type 2 Diabetes : a Randomized, Double-blind, Placebo-controlled, Cross-over Trial"

Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged over the past decade as a post-transcriptional regulator of the LDL receptor (LDL-R). PCSK9 acts as an endogenous natural inhibitor of the LDL-R pathway. Monoclonal antibodies (mAb) directed against PCSK9, such as Alirocumab, are the most common method of PCSK9 inhibition.

The goal of the present study is to assess, in the context of type 2 diabetes, a situation associated with an increased post-prandial hyperlipemia, whether PCSK9 inhibition with Alirocumab affects postprandial intestinal lipoprotein metabolism.

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

Recently, human monoclonal antibodies directed against PCSK9 have been shown to be effective in reducing LDL cholesterol. Besides the liver, little is known about the role of PCSK9 in the small intestine, a tissue where it is expressed at a high level. Preclinical studies in mice indicate that PCSK9 inhibition reduces post-prandial hyperlipemia.

Here, the investigators will test the effect of PCSK9 inhibition with alirocumab, a PCSK9 mAb, on post-prandial hyperlipemia in 24 patients with type 2 diabetes. The investigators will perform a randomized, double-blind, placebo-controlled, cross-over trial with alirocumab 75 mg every two weeks.

In the cross-over design, two periods of 10-weeks treatment (i.e. 5 injections) will be separated by a 10-week wash-out period to avoid carry-over effect. The primary endpoint will be the total area under the post-prandial triglycerides concentration-time curve from meal-time until 8h (AUC0-8h) after a standardized meal test. As secondary endpoints, the investigators will explore the effect of alirocumab on plasma lipids, markers of cholesterol absorption and synthesis, and glycemic parameters.

This study will help to decipher the function of PCSK9 on intestinal lipoprotein metabolism in human and to determine whether alirocumab can reduce post-prandial hyperlipemia, which is an independent cardiovascular risk factor. From a patient perspective, this study will give some important clues for the management of cardiovascular disease.

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.
22

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

  • France
      • Nantes, France, 44093
        • University Hospital of Nantes

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

18 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • Men with type 2 diabetes diagnosed since ≥ 6 months
  • HbA1C <9.0%
  • Men with primary hypercholesterolemia and/or mixed dyslipidemia
  • Aged 18-75 years (limits inclusive)
  • Patient could be treated for type 2 diabetes when diet and physical activity are not sufficient to restore glycemic control. The treatment must be stable 1 month before the inclusion and have to remain unchanged all along the study. The only authorized treatments are:
  • Metformin
  • And/or Sulphonylureas (SUs)
  • And/or Repaglinide
  • And/or DPP-4 inhibitors
  • And/or GLP1 receptor agonists: exenatide, liraglutide, dulaglutide
  • Fasting serum TG ≥ 150 mg/dl and < 500 mg/dl
  • BMI: 20-45 kg/m2
  • Use of statins or ezetimibe is allowed if treatment is stable for ≥ 1 month before the screening

Exclusion Criteria:

  • Any secondary causes of hypercholesterolemia or of mixed dyslipidemia (nephrotic syndrome, hypothyroidism…)
  • impaired liver function (AST and/or ALT ≥ 3ULN)
  • impaired renal function (eGFR with CKD-EPI formula < 30 ml/min)
  • Alcohol abuse (> 2 standard alcoholic drink per day; 1 standard alcoholic drink is the equivalent of 10g of alcohol)
  • History of myocardial infarction, acute coronary syndrome, unstable angina pectoris, stroke, transient ischemic attack, or cardiac revascularization within the 6 months before the screening visit.
  • History of PCSK9 mAb use
  • Known sensitivity to monoclonal antibody therapeutics or to their excipients
  • Lipid lowering therapies (other than statins), including fibrates, omega-3 fatty acids, bile acid sequestrants, niacin.
  • Insulin-treated patients
  • History of bariatric surgery
  • Inflammatory bowel diseases and gastrointestinal malabsorption diseases
  • Uncontrolled hypothyroidism (TSH > ULN and Free T4 < ULN) or hyperthyroidism (TSH < ULN)
  • Active cancer: progressive cancer or remission ≤ 3 years, except for basal or squamous cell carcinoma of the skin that has been successfully treated
  • Known history of positive test for HIV, hepatitis C or chronic hepatitis B
  • Corticosteroids therapy
  • Minors
  • Adults under guardianship or trusteeship

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: QUADRUPLE

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.
EXPERIMENTAL: Alirocumab
Alirocumab 75 mg for subcutaneous injection via a pre-filled pen. One injection every 2 weeks during a 10-weeks period (5 injections in total)
Drug: Alirocumab
prefilled pen containing 75 mg of Praluent (Alirocumab) in 1 ml of solution
PLACEBO_COMPARATOR: Placebo

Placebo matching alirocumab is prepared in the same formulation as alirocumab, without the addition of protein, for subcutaneous injection via a pre-filled pen.

One injection every 2 weeks during a 10-weeks period (5 injections in total)
Other: Placebo
prefilled pen containing 1 ml of solution without Praluent

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
Total area under the post-prandial triglycerides concentration-time curve from meal-time until 8h (AUC0-8h) after standardized high fat meal.
Time Frame: During 8 hours at week 10 after first treatment injection
Fifteenth days after the fifth injection of treatment (thus 10 weeks after first injection of treatment), subjects will be reported to investigational site (after a 12 hours overnight fast). Subjects must consume the test meal within 15 min. Upon completion of the meal (T0), sequential postprandial measurements of triglycerides concentrations will be taken. Blood samples will be collected at T-15, every 30 min for the first two hours after meal consumption, thereafter in 60 min intervals from T120 until 240 min and thereafter in 120 min intervals from T240 until 480 min.
During 8 hours at week 10 after first treatment injection

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
Effect of treatment with alirocumab versus placebo following a standardized high-fat meal on post-prandial lipid metabolism (plasma lipoproteins, apolipoproteins, ...)
Time Frame: During 8 hours at week 10 after first treatment injection
Fifteenth days after the fifth injection of treatment (thus 10 weeks after first injection of treatment), subjects will be reported to investigational site (after a 12 hours overnight fast). Subjects must consume the test meal within 15 min. Upon completion of the meal (T0), sequential postprandial measurements of triglycerides concentrations will be taken. Bleed samples will be collected at T-15, every 30 min for the first two hours after meal consumption, thereafter in 60 min intervals from T120 until 240 min and thereafter in 120 min intervals from T240 until 480 min.
During 8 hours at week 10 after first treatment injection
Effect of treatment with alirocumab versus placebo on fasting lipid metabolism following a standardized high fat meal, using the same biomarkers than those used in the post-prandial state, plus indirect markers of cholesterol absorption and synthesis
Time Frame: 10 weeks after treatment first injection
Fifteenth days after the fifth injection of treatment (thus 10 weeks after first injection of treatment), subjects will be reported to investigational site after a 12 hours overnight fast. Before ingestion of the high fat meal, blood sample will be removed to perform the analysis.
10 weeks after treatment first injection
Effect of treatment with alirocumab versus placebo on fasting and post-prandial and glucose homeostasis following a standardized high-fat meal
Time Frame: Before and during 8 hours after high fat meal at week 10 after first treatment injection
Fasting self-monitored blood glucose test will be obtained before starting the meal and every hour during 8 hours .
Before and during 8 hours after high fat meal at week 10 after first treatment injection

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.
Nantes University Hospital

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.
Regeneron Pharmaceuticals

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 Chair: Bertrand CARIOU, Nantes University Hospital

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.
February 12, 2019

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.
April 28, 2022

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.
April 28, 2022

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).
October 31, 2017

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.
November 13, 2017

First Posted (ACTUAL)

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.
November 17, 2017

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.
September 27, 2022

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.
September 26, 2022

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.
September 1, 2022

More Information

Terms related to this study

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.
  • RC16_0406

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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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