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

Primary Purpose

Diabetes, Heart Failure

Status
Completed
Phase
Phase 4
Locations
Denmark
Study Type
Interventional
Intervention
Entresto
Sitagliptin 100mg
Placebos
Sponsored by
Nicolai Jacob Wewer Albrechtsen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetes focused on measuring GLP-1, Neprilysin, DPP-4

Eligibility Criteria

18 Years - 30 Years (Adult)MaleAccepts Healthy Volunteers

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

Sites / Locations

  • University of Copenhagen

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Placebo Comparator

Active Comparator

Active Comparator

Active Comparator

Arm Label

Placebo

Entrestro as single dose

Sitagliptin as single dose

Entrestro + sitagliptin as single dose

Arm Description

No treatment. Participants are subjected to a standardized meal

194 mg sacubitril / 206 mg valstartan (entresto) as one single dose followed by a standardized meal

200mg sitagliptin (100mg the night before and 100mg on the study day) as one single dose followed by a standardized meal

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

C-peptide
changes in C-peptide using immunological methods
Glucagon
Changes in Plasma glucagon concentrations using different analytical methodologies

Full Information

First Posted
September 20, 2018
Last Updated
July 3, 2019
Sponsor
Nicolai Jacob Wewer Albrechtsen
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1. Study Identification

Unique Protocol Identification Number
NCT03717688
Brief Title
The Effects of Neprilysin on Glucagon-like Peptide-1
Acronym
NEP
Official Title
The Effects of Neprilysin on Glucagon-like Peptide-1
Study Type
Interventional

2. Study Status

Record Verification Date
July 2019
Overall Recruitment Status
Completed
Study Start Date
May 17, 2018 (Actual)
Primary Completion Date
February 1, 2019 (Actual)
Study Completion Date
May 14, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Nicolai Jacob Wewer Albrechtsen

4. Oversight

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
Data Monitoring Committee
No

5. 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
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes, Heart Failure
Keywords
GLP-1, Neprilysin, DPP-4

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Model Description
The participants are on 4 study days with wash out period of minimum 2 weeks randomized to 4 intervention arms
Masking
None (Open Label)
Allocation
Randomized
Enrollment
19 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
No treatment. Participants are subjected to a standardized meal
Arm Title
Entrestro as single dose
Arm Type
Active Comparator
Arm Description
194 mg sacubitril / 206 mg valstartan (entresto) as one single dose followed by a standardized meal
Arm Title
Sitagliptin as single dose
Arm Type
Active Comparator
Arm Description
200mg sitagliptin (100mg the night before and 100mg on the study day) as one single dose followed by a standardized meal
Arm Title
Entrestro + sitagliptin as single dose
Arm Type
Active Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Entresto
Other Intervention Name(s)
ARNI, Neprilysin inhibibitor
Intervention Description
Single dose administration of Entrestro 194 mg sacubitril / 206 mg valstartan
Intervention Type
Drug
Intervention Name(s)
Sitagliptin 100mg
Other Intervention Name(s)
DPP-4 inhibitor
Intervention Description
2 x 100mg sitagliptin as single dose.
Intervention Type
Drug
Intervention Name(s)
Placebos
Other Intervention Name(s)
placebo
Intervention Description
No treatment
Primary Outcome Measure Information:
Title
GLP-1
Description
changes in plasma GLP-1 using immunological methods: intact and total GLP-1
Time Frame
3 hours after treatment ( during the subsequent standardized meal)
Secondary Outcome Measure Information:
Title
C-peptide
Description
changes in C-peptide using immunological methods
Time Frame
3 hours after treatment ( during the subsequent standardized meal)
Title
Glucagon
Description
Changes in Plasma glucagon concentrations using different analytical methodologies
Time Frame
3 hours after treatment ( during the subsequent standardized meal)
Other Pre-specified Outcome Measures:
Title
Blood glucose
Description
changes in blood glucose using immunological methods
Time Frame
3 hours after treatment and during the subsequent standardized meal
Title
GIP
Description
changes in plasma GIP using immunological methods
Time Frame
3 hours after treatment ( during the subsequent standardized meal)

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
30 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Facility Information:
Facility Name
University of Copenhagen
City
Copenhagen
ZIP/Postal Code
2100
Country
Denmark

12. IPD Sharing Statement

Plan to Share IPD
Undecided
IPD Sharing Plan Description
undecided
Citations:
PubMed Identifier
31074791
Citation
Wewer Albrechtsen NJ, Mark PD, Terzic D, Hansen LH, Andersen UO, Hartmann B, Carr RD, Gustafsson F, Deacon CF, Holst JJ, Goetze JP, Plomgaard P. Sacubitril/Valsartan Augments Postprandial Plasma Concentrations of Active GLP-1 When Combined With Sitagliptin in Men. J Clin Endocrinol Metab. 2019 Sep 1;104(9):3868-3876. doi: 10.1210/jc.2019-00515.
Results Reference
result
PubMed Identifier
35175317
Citation
Thonsgaard S, Prickett TCR, Hansen LH, Wewer Albrechtsen NJ, Andersen UO, Terzic D, Plomgaard P, Gustafsson F, Goetze JP, Mark PD. Circulating Concentrations of C-Type Natriuretic Peptides Increase with Sacubitril/Valsartan Treatment in Healthy Young Men. Clin Chem. 2022 May 18;68(5):713-720. doi: 10.1093/clinchem/hvac005.
Results Reference
derived

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The Effects of Neprilysin on Glucagon-like Peptide-1

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