DiabetesPhase 4NEPNCT03717688
The Effects of Neprilysin on Glucagon-like Peptide-1
A Phase 4 study testing Entresto and Sitagliptin 100mg in people with Diabetes and Heart Failure, run by Nicolai Jacob Wewer Albrechtsen at 1 site in Denmark.
Trial summary
In the current study we wish to investigate the effects on glucagon-like peptide-1 (GLP-1) of a neprilysin inhibitor Read more about this study
- Who is it for?
- Ages 18 to 30 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Diabetes, Heart Failure
- What is being tested?
- Entresto and Sitagliptin 100mg
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 19 participants
- Where
- 1 siteDenmark
- Study dates
- 17 May 2018to 14 May 2019
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 30 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- men
- body mass index between 20-25
Who cannot join
- acute diseases within the two weeks
- chronic diseases
- smoker
- alcoholism, drug addiction or recent weight loss
- blood donation within the last 3 months
Trial locations and contacts
1 site in 1 country.
About this study
In the current study we wish to investigate the effects on glucagon-like peptide-1 (GLP-1) of a neprilysin inhibitor
Read the 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
- Conditions
- Diabetes, Heart Failure
- Being tested
- Entresto, Sitagliptin 100mg, Placebos
- Keywords
- GLP-1, Neprilysin, DPP-4
- Medical subject headings
- Diabetes Mellitus, Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EntrestoDrug
Also called ARNI, Neprilysin inhibibitor
Single dose administration of Entrestro 194 mg sacubitril / 206 mg valstartan
Sitagliptin 100mgDrug
Also called DPP-4 inhibitor
2 x 100mg sitagliptin as single dose.
PlacebosDrug
Also called placebo
No treatment
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | No treatment. Participants are subjected to a standardized meal Receives: Drug: Placebos |
| Entrestro as single dose | Active comparator | 194 mg sacubitril / 206 mg valstartan (entresto) as one single dose followed by a standardized meal Receives: Drug: Entresto |
| Sitagliptin as single dose | Active comparator | 200mg sitagliptin (100mg the night before and 100mg on the study day) as one single dose followed by a standardized meal Receives: Drug: Sitagliptin 100mg |
| Entrestro + sitagliptin as single dose | 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 Receives: Drug: Entresto; Drug: Sitagliptin 100mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
GLP-1
changes in plasma GLP-1 using immunological methods: intact and total GLP-1
Measured: 3 hours after treatment ( during the subsequent standardized meal)
Secondary outcomes (2)
C-peptide
changes in C-peptide using immunological methods
Measured: 3 hours after treatment ( during the subsequent standardized meal)
Glucagon
Changes in Plasma glucagon concentrations using different analytical methodologies
Measured: 3 hours after treatment ( during the subsequent standardized meal)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2018
- Study start17 May 2018
- Primary completion1 Feb 2019
- Study completion14 May 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for DiabetesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- 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)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nicolai Jacob Wewer Albrechtsen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Nicolai Jacob Wewer Albrechtsen, University of Copenhagen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03717688
- Sponsor's protocol ID
- NEP and GLP-1
- Acronym
- NEP
- Status last verified
- Jul 2019
- First submitted
- 20 Sep 2018
- Last updated
- 8 Jul 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: undecided
Publications
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.
PubMed 31074791Thonsgaard 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.
PubMed 35175317
Study at a glance
From the registry record, last updated by the sponsor on 8 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Neprilysin on Glucagon-like Peptide-1
- ClinicalTrials.gov ID
- NCT03717688
- Acronym / sponsor ID
- NEP / NEP and GLP-1
- Conditions
- Diabetes, Heart Failure
- Keywords
- GLP-1, Neprilysin, DPP-4
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Nicolai Jacob Wewer AlbrechtsenUniversity, hospital or other
- Study start
- 17 May 2018 (actual)
- Primary completion
- 1 Feb 2019 (actual)
- Study completion
- 14 May 2019 (actual)
- First posted
- 24 Oct 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- The participants are on 4 study days with wash out period of minimum 2 weeks randomized to 4 intervention arms
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlacebosNo treatment. Participants are subjected to a standardized meal |
| Entrestro as single dose | Active comparator | Drug: Entresto194 mg sacubitril / 206 mg valstartan (entresto) as one single dose followed by a standardized meal |
| Sitagliptin as single dose | Active comparator | Drug: Sitagliptin 100mg200mg sitagliptin (100mg the night before and 100mg on the study day) as one single dose followed by a standardized meal |
| Entrestro + sitagliptin as single dose | Active comparator | Drug: Entresto, Drug: Sitagliptin 100mg194 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 |
Who may qualify
- Ages
- 18 to 30 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- men
- body mass index between 20-25
Key exclusion criteria (5 listed)
- acute diseases within the two weeks
- chronic diseases
- smoker
- alcoholism, drug addiction or recent weight loss
- blood donation within the last 3 months
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EntrestoAlso: ARNI, Neprilysin inhibibitorSingle dose administration of Entrestro 194 mg sacubitril / 206 mg valstartan | Drug | Entrestro + sitagliptin as single dose, Entrestro as single dose |
| Sitagliptin 100mgAlso: DPP-4 inhibitor2 x 100mg sitagliptin as single dose. | Drug | Entrestro + sitagliptin as single dose, Sitagliptin as single dose |
| PlacebosAlso: placeboNo treatment | Drug | Placebo |
Primary outcome
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
2 secondary outcomes
C-peptide
Time frame: 3 hours after treatment ( during the subsequent standardized meal)
Glucagon
Time frame: 3 hours after treatment ( during the subsequent standardized meal)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jul 2019.
- Results publication: PubMed 31074791Wewer 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.
- Derived from this study: PubMed 35175317Thonsgaard 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.
- Individual participant dataSharing planned: Undecided. undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Entresto and Sitagliptin 100mg in people with Diabetes and Heart Failure, run by Nicolai Jacob Wewer Albrechtsen at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
GLP-1 (time frame: 3 hours after treatment ( during the subsequent standardized meal)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03717688, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jul 2019.