NEPT2D: Effect of Neprilysin on Glucagon-Like Peptide-1 in Patients With Type 2 Diabetes

• Sponsor: University of Copenhagen (Other)
• Overall Status: Completed
• CT.gov ID: NCT03893526
• Collaborator: Hvidovre University Hospital (Other)
• Enrollment: 12
• Location: 1
• Arms: 5
• Actual Duration (Months): 25.2
• Patients Per Site Per Month: 0.5

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Type2 Diabetes	Drug: Entresto; Drug: Sitagliptin; Drug: Valsartan; Drug: Placebo	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: The Effect of Neprilysin on Plasma Concentrations of Glucagon-Like Peptide-1 in Patients With Type 2 Diabetes
• Actual Study Start Date: Jan 25, 2019
• Actual Primary Completion Date: Mar 1, 2021
• Actual Study Completion Date: Mar 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Participants are subjected to a standardized meal	Drug: Placebo; placebo day
Active Comparator: Entrestro 194 mg sacubitril / 206 mg valstartan (entresto) as one single dose followed by a standardized meal	Drug: Entresto; Single dose administration of entresto
Active Comparator: Sitagliptin 200mg sitagliptin (100mg the night before and 100mg on the study day) as one single dose followed by a standardized meal	Drug: Sitagliptin; Single dose administration of sitagliptin
Active Comparator: Entrestro + sitagliptin 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 entresto; Drug: Sitagliptin; Single dose administration of sitagliptin
Active Comparator: Valsartan 206mg valsartan as one single dose followed by a standardized meal	Drug: Valsartan; single doses administration of valsartan

Outcome Measures

Primary Outcome Measures

1. Blood Glucose [3 hours after treatment ( during the subsequent standardized meal)]

   Plasma Concentrations of glucose

Secondary Outcome Measures

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

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

3. Plasma Concentrations of Glucagon [3 hours after treatment ( during the subsequent standardized meal)]

4. Plasma Concentrations of Insulin [3 hours after treatment ( during the subsequent standardized meal)]

5. Plasma Concentrations of C-Peptide [3 hours after treatment ( during the subsequent standardized meal)]

6. Plasma Concentrations of Amino Acids [3 hours after treatment ( during the subsequent standardized meal)]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 30 Years to 70 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Type 2 Diabetes

• Oral Antidiabetics Medicine Only

• Body Mass Index of 25-35

• Type 2 Diabetes

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	Hvidovre Hospital	Hvidovre	RegionH	Denmark	2650

Sponsors and Collaborators

• University of Copenhagen
• Hvidovre University Hospital

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Nicolai Jacob Wewer Albrechtsen, Resident, University of Copenhagen
• ClinicalTrials.gov Identifier: NCT03893526
• Other Study ID Numbers: NEPT2D
• First Posted: Mar 28, 2019
• Last Update Posted: May 5, 2021
• Last Verified: May 1, 2021

• 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
• Keywords provided by Nicolai Jacob Wewer Albrechtsen, Resident, University of Copenhagen: GLP-1; Neprilysin; Diabetes
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Sitagliptin Phosphate; Valsartan; Sacubitril and valsartan sodium hydrate drug combination

Study Results

No Results Posted as of May 5, 2021