The Effects of Neprilysin on Glucagon-like Peptide-1 (NEP)

July 3, 2019 updated by: Nicolai Jacob Wewer Albrechtsen
In the current study we wish to investigate the effects on glucagon-like peptide-1 (GLP-1) of a neprilysin inhibitor

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Glucagon-like peptide-1(GLP-1) is secreted during a meal and increases glucose induced insulin secretion. The enzyme dipeptidyl peptidase 4(DPP-4) cleaves intact GLP-1 within minutes and DPP-4 inhibitors are therefore used for treatment of diabetic hyperglycemia. A few animal studies have implicated the enzyme neutral endopeptidase 24.11 (24.11) in the degradation of GLP-1 but if this is the case in humans is unknown. We therefore administered a NEP inhibitor, 194mg sacubitril, a DPP-4 inhibitor (sitagliptin 100mg the night before and 100mg 2 hours before), both, or place, to nine healthy men during a standardized meal and measured plasma concentrations of GLP-1

Study Type

Interventional

Enrollment (Actual)

19

Phase

  • Phase 4

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

  • Denmark
      • Copenhagen, Denmark, 2100
        • University of Copenhagen

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

Ages Eligible for Study

18 years to 30 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • men
  • body mass index between 20-25

Exclusion Criteria:

  • acute diseases within the two weeks
  • chronic diseases
  • smoker
  • alcoholism, drug addiction or recent weight loss
  • blood donation within the last 3 months

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 Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
No treatment. Participants are subjected to a standardized meal
Drug: Placebos
No treatment
Other Names:
  • placebo
Active Comparator: Entrestro as single dose
194 mg sacubitril / 206 mg valstartan (entresto) as one single dose followed by a standardized meal
Drug: Entresto
Single dose administration of Entrestro 194 mg sacubitril / 206 mg valstartan
Other Names:
  • ARNI
  • Neprilysin inhibibitor
Active Comparator: Sitagliptin as single dose
200mg sitagliptin (100mg the night before and 100mg on the study day) as one single dose followed by a standardized meal
Drug: Sitagliptin 100mg
2 x 100mg sitagliptin as single dose.
Other Names:
  • DPP-4 inhibitor
Active Comparator: Entrestro + sitagliptin as single dose
194 mg sacubitril / 206 mg valstartan (entresto) + 200mg sitagliptin (100mg the night before and 100mg on the study day) as one single dose followed by a standardized meal
Drug: Entresto
Single dose administration of Entrestro 194 mg sacubitril / 206 mg valstartan
Other Names:
  • ARNI
  • Neprilysin inhibibitor
Drug: Sitagliptin 100mg
2 x 100mg sitagliptin as single dose.
Other Names:
  • DPP-4 inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
GLP-1
Time Frame: 3 hours after treatment ( during the subsequent standardized meal)
changes in plasma GLP-1 using immunological methods: intact and total GLP-1
3 hours after treatment ( during the subsequent standardized meal)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
C-peptide
Time Frame: 3 hours after treatment ( during the subsequent standardized meal)
changes in C-peptide using immunological methods
3 hours after treatment ( during the subsequent standardized meal)
Glucagon
Time Frame: 3 hours after treatment ( during the subsequent standardized meal)
Changes in Plasma glucagon concentrations using different analytical methodologies
3 hours after treatment ( during the subsequent standardized meal)

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Blood glucose
Time Frame: 3 hours after treatment and during the subsequent standardized meal
changes in blood glucose using immunological methods
3 hours after treatment and during the subsequent standardized meal
GIP
Time Frame: 3 hours after treatment ( during the subsequent standardized meal)
changes in plasma GIP using immunological methods
3 hours after treatment ( during the subsequent standardized meal)

Collaborators and Investigators

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

Sponsor

Nicolai Jacob Wewer Albrechtsen

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)

May 17, 2018

Primary Completion (Actual)

February 1, 2019

Study Completion (Actual)

May 14, 2019

Study Registration Dates

First Submitted

September 20, 2018

First Submitted That Met QC Criteria

October 23, 2018

First Posted (Actual)

October 24, 2018

Study Record Updates

Last Update Posted (Actual)

July 8, 2019

Last Update Submitted That Met QC Criteria

July 3, 2019

Last Verified

July 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NEP and GLP-1

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

IPD Plan Description

undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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