Type2 DiabetesPhase 4NEPT2DNCT03893526
Effect of Neprilysin on Glucagon-Like Peptide-1 in Patients With Type 2 Diabetes
A Phase 4 study testing Entresto, Sitagliptin and Valsartan in people with Type2 Diabetes, run by University of Copenhagen at 1 site in Denmark.
Trial 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. Read more about this study
- Who is it for?
- Ages 30 to 70 years, men only
- Conditions the study is for
- Type2 Diabetes
- What is being tested?
- Entresto, Sitagliptin and Valsartan
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 1 siteDenmark
- Study dates
- 25 Jan 2019to 1 Mar 2021
- 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 30 to 70 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Type 2 Diabetes
- Oral Antidiabetics Medicine Only
- Body Mass Index of 25-35
- Type 2 Diabetes
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
Official title: The Effect of Neprilysin on Plasma Concentrations of Glucagon-Like Peptide-1 in Patients With Type 2 Diabetes
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
- Conditions
- Type2 Diabetes
- Being tested
- Entresto, Sitagliptin, Valsartan, Placebo
- Keywords
- GLP-1, Neprilysin, Diabetes
- Medical subject headings
- Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EntrestoDrug
Single dose administration of entresto
SitagliptinDrug
Single dose administration of sitagliptin
ValsartanDrug
single doses administration of valsartan
PlaceboDrug
placebo day
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Participants are subjected to a standardized meal Receives: Drug: Placebo |
| Entrestro | Active comparator | 194 mg sacubitril / 206 mg valstartan (entresto) as one single dose followed by a standardized meal Receives: 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 Receives: 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 Receives: Drug: Entresto; Drug: Sitagliptin |
| Valsartan | Active comparator | 206mg valsartan as one single dose followed by a standardized meal Receives: Drug: Valsartan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Blood Glucose
Plasma Concentrations of glucose
Measured: 3 hours after treatment ( during the subsequent standardized meal)
Secondary outcomes (6)
Plasma Concentrations of GLP-1
Measured: 3 hours after treatment ( during the subsequent standardized meal)
Plasma Concentrations of GIP
Measured: 3 hours after treatment ( during the subsequent standardized meal)
Plasma Concentrations of Glucagon
Measured: 3 hours after treatment ( during the subsequent standardized meal)
Plasma Concentrations of Insulin
Measured: 3 hours after treatment ( during the subsequent standardized meal)
Plasma Concentrations of C-Peptide
Measured: 3 hours after treatment ( during the subsequent standardized meal)
Plasma Concentrations of Amino Acids
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 posted28 Mar 2019
- Study start25 Jan 2019
- Primary completion1 Mar 2021
- Study completion1 Mar 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Type2 DiabetesStudies of the same condition, open and under way.
- More trials run by University of CopenhagenThe sponsor's other registered studies.
- 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
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Copenhagen
- Sponsor type
- University, hospital or other
- Collaborators
- Hvidovre University Hospital
- Responsible party
- Principal investigator, Nicolai Jacob Wewer Albrechtsen, University of Copenhagen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03893526
- Sponsor's protocol ID
- NEPT2D
- Acronym
- NEPT2D
- Status last verified
- May 2021
- First submitted
- 26 Mar 2019
- Last updated
- 5 May 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Undecided
Publications
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.
PubMed 35676803
Study at a glance
From the registry record, last updated by the sponsor on 5 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Neprilysin on Plasma Concentrations of Glucagon-Like Peptide-1 in Patients With Type 2 Diabetes
- ClinicalTrials.gov ID
- NCT03893526
- Acronym / sponsor ID
- NEPT2D / NEPT2D
- Conditions
- Type2 Diabetes
- Keywords
- GLP-1, Neprilysin, Diabetes
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- University of CopenhagenUniversity, hospital or other
- Collaborators
- Hvidovre University Hospital
- Study start
- 25 Jan 2019 (actual)
- Primary completion
- 1 Mar 2021 (actual)
- Study completion
- 1 Mar 2021 (actual)
- First posted
- 28 Mar 2019 (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.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboParticipants are subjected to a standardized meal |
| Entrestro | Active comparator | Drug: Entresto194 mg sacubitril / 206 mg valstartan (entresto) as one single dose followed by a standardized meal |
| Sitagliptin | Active comparator | Drug: Sitagliptin200mg sitagliptin (100mg the night before and 100mg on the study day) as one single dose followed by a standardized meal |
| Entrestro + sitagliptin | Active comparator | Drug: Entresto, Drug: Sitagliptin194 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 |
| Valsartan | Active comparator | Drug: Valsartan206mg valsartan as one single dose followed by a standardized meal |
Who may qualify
- Ages
- 30 to 70 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Type 2 Diabetes
- Oral Antidiabetics Medicine Only
- Body Mass Index of 25-35
- Type 2 Diabetes
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 |
|---|---|---|
| EntrestoSingle dose administration of entresto | Drug | Entrestro, Entrestro + sitagliptin |
| SitagliptinSingle dose administration of sitagliptin | Drug | Entrestro + sitagliptin, Sitagliptin |
| Valsartansingle doses administration of valsartan | Drug | Valsartan |
| Placeboplacebo day | Drug | Placebo |
Primary outcome
Blood Glucose
Time frame: 3 hours after treatment ( during the subsequent standardized meal)
Plasma Concentrations of glucose
6 secondary outcomes
Plasma Concentrations of GLP-1
Time frame: 3 hours after treatment ( during the subsequent standardized meal)
Plasma Concentrations of GIP
Time frame: 3 hours after treatment ( during the subsequent standardized meal)
Plasma Concentrations of Glucagon
Time frame: 3 hours after treatment ( during the subsequent standardized meal)
Plasma Concentrations of Insulin
Time frame: 3 hours after treatment ( during the subsequent standardized meal)
Plasma Concentrations of C-Peptide
Time frame: 3 hours after treatment ( during the subsequent standardized meal)
Plasma Concentrations of Amino Acids
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 5 May 2021.
- Derived from this study: PubMed 35676803Wewer 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.
- 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, Sitagliptin and Valsartan in people with Type2 Diabetes, run by University of Copenhagen 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 4 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 5 May 2021. 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?
Blood Glucose (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 NCT03893526, which also lists 1 linked publication.
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 5 May 2021.