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NEP: The Effects of Neprilysin on Glucagon-like Peptide-1

Sponsor
Nicolai Jacob Wewer Albrechtsen (Other)
Overall Status
Completed
CT.gov ID
NCT03717688
Collaborator
(none)
19
Enrollment
1
Location
4
Arms
11.9
Actual Duration (Months)
1.6
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

In the current study we wish to investigate the effects on glucagon-like peptide-1 (GLP-1) of a neprilysin inhibitor

Condition or Disease Intervention/Treatment Phase
Phase 4

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 Design

Study Type:
Interventional
Actual Enrollment :
19 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Intervention Model Description:
The participants are on 4 study days with wash out period of minimum 2 weeks randomized to 4 intervention armsThe participants are on 4 study days with wash out period of minimum 2 weeks randomized to 4 intervention arms
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
The Effects of Neprilysin on Glucagon-like Peptide-1
Actual Study Start Date :
May 17, 2018
Actual Primary Completion Date :
Feb 1, 2019
Actual Study Completion Date :
May 14, 2019

Arms and Interventions

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. GLP-1 [3 hours after treatment ( during the subsequent standardized meal)]

      changes in plasma GLP-1 using immunological methods: intact and total GLP-1

    Secondary Outcome Measures

    1. C-peptide [3 hours after treatment ( during the subsequent standardized meal)]

      changes in C-peptide using immunological methods

    2. Glucagon [3 hours after treatment ( during the subsequent standardized meal)]

      Changes in Plasma glucagon concentrations using different analytical methodologies

    Other Outcome Measures

    1. Blood glucose [3 hours after treatment and during the subsequent standardized meal]

      changes in blood glucose using immunological methods

    2. GIP [3 hours after treatment ( during the subsequent standardized meal)]

      changes in plasma GIP using immunological methods

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 30 Years
    Sexes Eligible for Study:
    Male
    Accepts Healthy Volunteers:
    Yes
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Copenhagen Copenhagen Denmark 2100

    Sponsors and Collaborators

    • Nicolai Jacob Wewer Albrechtsen

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Nicolai Jacob Wewer Albrechtsen, Junior Consultant, University of Copenhagen
    ClinicalTrials.gov Identifier:
    NCT03717688
    Other Study ID Numbers:
    • NEP and GLP-1
    First Posted:
    Oct 24, 2018
    Last Update Posted:
    Jul 8, 2019
    Last Verified:
    Jul 1, 2019
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    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
    Keywords provided by Nicolai Jacob Wewer Albrechtsen, Junior Consultant, University of Copenhagen
    GLP-1
    Neprilysin
    DPP-4
    Additional relevant MeSH terms:
    Heart Failure
    Sitagliptin Phosphate
    Dipeptidyl-Peptidase IV Inhibitors
    Sacubitril and valsartan sodium hydrate drug combination

    Study Results

    No Results Posted as of Jul 8, 2019