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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03717688
Recruitment Status : Completed
First Posted : October 24, 2018
Last Update Posted : July 8, 2019
Sponsor:
Information provided by (Responsible Party):
Nicolai Jacob Wewer Albrechtsen, University of Copenhagen

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
Diabetes Heart Failure Drug: Entresto Drug: Sitagliptin 100mg Drug: Placebos 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

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Study Type : Interventional  (Clinical Trial)
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 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 : February 1, 2019
Actual Study Completion Date : May 14, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: Placebo
No treatment. Participants are subjected to a standardized meal
Drug: Placebos
No treatment
Other Name: 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 Name: 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 Name: DPP-4 inhibitor




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. C-peptide [ Time Frame: 3 hours after treatment ( during the subsequent standardized meal) ]
    changes in C-peptide using immunological methods

  2. Glucagon [ Time Frame: 3 hours after treatment ( during the subsequent standardized meal) ]
    Changes in Plasma glucagon concentrations using different analytical methodologies


Other Outcome Measures:
  1. Blood glucose [ Time Frame: 3 hours after treatment and during the subsequent standardized meal ]
    changes in blood glucose using immunological methods

  2. GIP [ Time Frame: 3 hours after treatment ( during the subsequent standardized meal) ]
    changes in plasma GIP using immunological methods



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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03717688


Locations
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Denmark
University of Copenhagen
Copenhagen, Denmark, 2100
Sponsors and Collaborators
Nicolai Jacob Wewer Albrechtsen

Publications of Results:
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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: October 24, 2018    Key Record Dates
Last Update Posted: July 8, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: undecided

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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, University of Copenhagen:
GLP-1
Neprilysin
DPP-4
Additional relevant MeSH terms:
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Heart Failure
Heart Diseases
Cardiovascular Diseases
Sitagliptin Phosphate
Glucagon
Glucagon-Like Peptide 1
LCZ 696
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Gastrointestinal Agents
Angiotensin Receptor Antagonists