NCT03893526

Brief Summary

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 with type 2 diabetes 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 placebo, to patients with type 2 diabetes during a standardized meal and measured plasma concentrations of GLP-1

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
12

participants targeted

Target at below P25 for phase_4

Timeline
Completed

Started Jan 2019

Typical duration for phase_4

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 25, 2019

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

March 26, 2019

Completed
2 days until next milestone

First Posted

Study publicly available on registry

March 28, 2019

Completed
1.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2021

Completed
Last Updated

May 5, 2021

Status Verified

May 1, 2021

Enrollment Period

2.1 years

First QC Date

March 26, 2019

Last Update Submit

May 4, 2021

Conditions

Type2 Diabetes

Keywords

GLP-1NeprilysinDiabetes

Outcome Measures

Primary Outcomes (1)

  • Blood Glucose

    Plasma Concentrations of glucose

    3 hours after treatment ( during the subsequent standardized meal)

Secondary Outcomes (6)

  • Plasma Concentrations of GLP-1

    3 hours after treatment ( during the subsequent standardized meal)

  • Plasma Concentrations of GIP

    3 hours after treatment ( during the subsequent standardized meal)

  • Plasma Concentrations of Glucagon

    3 hours after treatment ( during the subsequent standardized meal)

  • Plasma Concentrations of Insulin

    3 hours after treatment ( during the subsequent standardized meal)

  • Plasma Concentrations of C-Peptide

    3 hours after treatment ( during the subsequent standardized meal)

  • +1 more secondary outcomes

Study Arms (5)

Placebo

PLACEBO COMPARATOR

Participants are subjected to a standardized meal

Drug: Placebo

Entrestro

ACTIVE COMPARATOR

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

Drug: Entresto

Sitagliptin

ACTIVE COMPARATOR

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

Drug: Sitagliptin

Entrestro + sitagliptin

ACTIVE COMPARATOR

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: EntrestoDrug: Sitagliptin

Valsartan

ACTIVE COMPARATOR

206mg valsartan as one single dose followed by a standardized meal

Drug: Valsartan

Interventions

EntrestoDRUG

Single dose administration of entresto

EntrestroEntrestro + sitagliptin
SitagliptinDRUG

Single dose administration of sitagliptin

Entrestro + sitagliptinSitagliptin
ValsartanDRUG

single doses administration of valsartan

Valsartan
PlaceboDRUG

placebo day

Placebo

Eligibility Criteria

Age30 Years - 70 Years
Sexmale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Type 2 Diabetes
  • Oral Antidiabetics Medicine Only
  • Body Mass Index of 25-35
  • Type 2 Diabetes

You may not qualify if:

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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Hvidovre Hospital

Hvidovre, RegionH, 2650, Denmark

Location

Related Publications (1)

  • Wewer Albrechtsen NJ, Moller A, Martinussen C, Gluud LL, Rashu EB, Richter MM, Plomgaard P, Goetze JP, Kjeldsen S, Hansen LH, Gustafsson F, Deacon CF, Holst JJ, Madsbad S, Bojsen-Moller KN. Acute effects on glucose tolerance by neprilysin inhibition in patients with type 2 diabetes. Diabetes Obes Metab. 2022 Oct;24(10):2017-2026. doi: 10.1111/dom.14789. Epub 2022 Jul 21.

    PMID: 35676803DERIVED

MeSH Terms

Conditions

Diabetes Mellitus

Interventions

sacubitril and valsartan sodium hydrate drug combinationSitagliptin PhosphateValsartan

Condition Hierarchy (Ancestors)

Glucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System Diseases

Intervention Hierarchy (Ancestors)

TriazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsPyrazinesTetrazolesValineAmino Acids, Branched-ChainAmino AcidsAmino Acids, Peptides, and ProteinsAmino Acids, Essential

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Resident

Study Record Dates

First Submitted

March 26, 2019

First Posted

March 28, 2019

Study Start

January 25, 2019

Primary Completion

March 1, 2021

Study Completion

March 1, 2021

Last Updated

May 5, 2021

Record last verified: 2021-05

Locations

DK(1)