Type 2 DiabetesNCT05575206
The Influence of Genetic Variations in ELAPOR1 or ELAPOR2 on Insulin Secretion and Glucose Regulation in Humans
An observational study of Type 2 Diabetes and Impaired Insulin Secretion, run by University Hospital Tuebingen at 1 site in Germany.
Trial summary
Insulin resistance and the depletion of insulin secretion are major pathogenetic aspects of type 2 diabetes mellitus. Recently, inceptor, a receptor on the surface of beta cells was dicovered. Inceptor promotes beta cell resistance to insulin and IGF-1. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Type 2 Diabetes, Impaired Insulin Secretion
- Type of treatment
- Pill or oral medicine
- How many people
- 20 participants
- Where
- 1 siteGermany
- Study dates
- 15 Sep 2023to 1 Mar 2025
- Phase
- Observational
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Subjects with genetic variations in ELAPOR1 and ELAPOR2
Who may be able to join
- Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures.
- subjects with genetic variations in ELAPOR1 and ELAPOR2
Who cannot join
- Women during pregnancy and lactation
- Treatment with any medication effecting on glucose metabolism like anti-diabetic drugs or steroids
- Any pancreatic disease
- Known current presence or history of severe neurological or psychiatric diseases, schizophrenia, bipolar disorder
Trial locations and contacts
1 site in 1 country.
Reiner Jumpertz-von Schwartzenberg, MD contact
Germany1 site, 1 recruiting
- Recruiting
University Hopsital Tübingen
Tübingen, 72076
Reiner Jumpertz-von Schwartzenberg, MD
About this study
Official title: Untersuchung Des Einflusses Von Genetischen Varianten in ELAPOR1 Oder ELAPOR2 Auf Die Insulinsekretion Und Glukoseregulation im Menschen
Insulin resistance and the depletion of insulin secretion are major pathogenetic aspects of type 2 diabetes mellitus. Recently, inceptor, a receptor on the surface of beta cells was dicovered. Inceptor promotes beta cell resistance to insulin and IGF-1.
In humans, the inceptor is encoded by the two genes ELAPOR1 and ELAPOR2. Whether functional mutations in these genes affect insulin secretion and glucose regulation in humans has not been investigated so far.
In this study we investigate the influence of genetic variations in ELAPOR1 or ELAPOR2 on insulin secretion and glucose regulation in humans by hygerglycemic glucose clamp technique and oral glucose tolerance test respectively.
Read the detailed description
Type 2 diabetes mellitus is a heterogenic disorder with a complex pathogenesis. Although, loss of beta cell function is crucial for the manifestation of the disease. Genome-wide association studies identified more than 400 genetic variations associated with a reduced beta cell function. Interestingly, beta cells are not only responsible for the secretion of insulin, but are also insulin sensitive cells, whereby insulin secretion and proliferation is regulated. It is well known that an insulin and insulin-like growth factor (IGF-1) resistance lead to the manifestation of type 2 diabetes. Underlying mechanism are mostly unknown. Recently, a new receptor on the surface of beta-cells was identified which mediates the resistance of beta cells to insulin and IGF-1. This insulin inhibitory receptor (Inceptor) induces its inhibitory function via clathrin-mediated endocytosis of the INSR-IGF-1R complex. In mice, inceptor is encoded by lir and its knock-out leads to beta cell proliferation and an increased insulin secretion. In animal models, treatment with monoclonal antibodies against the extracellular domain of inceptor, leads to a significantly improved glucose regulation. Thus, pharmacological interventions on the inceptor could represent a novel therapeutic approach for the treatment of type 2 diabetes mellitus. In humans, inceptor is encoded by genes ELAPOR1 and ELAPOR2. So far, there are no studies in humans that investigate if functional mutations in these genes affect insulin secretion and glucose regulation. The aim of this study is to investigate, whether subjects with genetic variants in ELAPOR1 or ELAPOR2 have altered insulin secretion and thus altered glucose regulation. For this purpose, the study results are compared with a reference cohort without variants in ELAPOR1 or ELAPOR2 (matched for age, sex, waist to hip ratio and BMI) from our databases of previous studies (e.g. PLIS: NCT01947595, PREG: NCT04270578, KNOMA: NCT04950283). Insulin secretion is assessed by hyperglycemic glucose clamp technique. An oral glucose tolerance test will be performed to assess glucose tolerance.
- Conditions
- Type 2 Diabetes, Impaired Insulin Secretion
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Patients with rare genetic variant in ELAPOR1 or ELAPOR2 | Patients undergo several examinations. Beside anthropometric measurements, bioelectrical impedance analysis, an 2h-oral glucose tolerance test (OGTT) and a hyperglycemic clamp is performed. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Insulin secretion capacity
Glucose stimulated insulin secretion adjusted for insulin sensitivity during an hyperglycemic clamp in subjects with genetic variants in ELAPOR1 and ELAPOR2 compared to a control cohort without genetic variants.
Measured: -15 minutes - 130 minutes
Secondary outcomes (1)
Glucose tolerance status
Glucose tolerance status examined by 2h-oral glucose tolerance test in subjects with genetic variants in ELAPOR1 and ELAPOR2 compared to a control cohort without genetic variants.
Measured: 0-120 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Oct 2022
- Study start15 Sep 2023
- Primary completion1 Oct 2024 (estimated)
- Study completion1 Mar 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 2 DiabetesStudies of the same condition, open and under way.
- More trials run by University Hospital TuebingenThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital Tuebingen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Reiner Jumpertz-von Schwartzenberg, MD, Principal investigator, University Hopsital Tübingen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05575206
- Sponsor's protocol ID
- INCEPTOR
- Status last verified
- Aug 2023
- First submitted
- 26 Sep 2022
- Last updated
- 25 Sep 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Untersuchung Des Einflusses Von Genetischen Varianten in ELAPOR1 Oder ELAPOR2 Auf Die Insulinsekretion Und Glukoseregulation im Menschen
- ClinicalTrials.gov ID
- NCT05575206
- Acronym / sponsor ID
- INCEPTOR
- Conditions
- Type 2 Diabetes, Impaired Insulin Secretion
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- University Hospital TuebingenUniversity, hospital or other
- Study start
- 15 Sep 2023 (actual)
- Primary completion
- 1 Oct 2024 (estimated)
- Study completion
- 1 Mar 2025 (estimated)
- First posted
- 12 Oct 2022 (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.
Insulin resistance and the depletion of insulin secretion are major pathogenetic aspects of type 2 diabetes mellitus. Recently, inceptor, a receptor on the surface of beta cells was dicovered. Inceptor promotes beta cell resistance to insulin and IGF-1.
In humans, the inceptor is encoded by the two genes ELAPOR1 and ELAPOR2. Whether functional mutations in these genes affect insulin secretion and glucose regulation in humans has not been investigated so far.
In this study we investigate the influence of genetic variations in ELAPOR1 or ELAPOR2 on insulin secretion and glucose regulation in humans by hygerglycemic glucose clamp technique and oral glucose tolerance test respectively.
Detailed description
Type 2 diabetes mellitus is a heterogenic disorder with a complex pathogenesis. Although, loss of beta cell function is crucial for the manifestation of the disease. Genome-wide association studies identified more than 400 genetic variations associated with a reduced beta cell function. Interestingly, beta cells are not only responsible for the secretion of insulin, but are also insulin sensitive cells, whereby insulin secretion and proliferation is regulated. It is well known that an insulin and insulin-like growth factor (IGF-1) resistance lead to the manifestation of type 2 diabetes. Underlying mechanism are mostly unknown. Recently, a new receptor on the surface of beta-cells was identified which mediates the resistance of beta cells to insulin and IGF-1. This insulin inhibitory receptor (Inceptor) induces its inhibitory function via clathrin-mediated endocytosis of the INSR-IGF-1R complex. In mice, inceptor is encoded by lir and its knock-out leads to beta cell proliferation and an increased insulin secretion. In animal models, treatment with monoclonal antibodies against the extracellular domain of inceptor, leads to a significantly improved glucose regulation. Thus, pharmacological interventions on the inceptor could represent a novel therapeutic approach for the treatment of type 2 diabetes mellitus. In humans, inceptor is encoded by genes ELAPOR1 and ELAPOR2. So far, there are no studies in humans that investigate if functional mutations in these genes affect insulin secretion and glucose regulation. The aim of this study is to investigate, whether subjects with genetic variants in ELAPOR1 or ELAPOR2 have altered insulin secretion and thus altered glucose regulation. For this purpose, the study results are compared with a reference cohort without variants in ELAPOR1 or ELAPOR2 (matched for age, sex, waist to hip ratio and BMI) from our databases of previous studies (e.g. PLIS: NCT01947595, PREG: NCT04270578, KNOMA: NCT04950283). Insulin secretion is assessed by hyperglycemic glucose clamp technique. An oral glucose tolerance test will be performed to assess glucose tolerance.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients with rare genetic variant in ELAPOR1 or ELAPOR2 | – | –Patients undergo several examinations. Beside anthropometric measurements, bioelectrical impedance analysis, an 2h-oral glucose tolerance test (OGTT) and a hyperglycemic clamp is performed. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Subjects with genetic variations in ELAPOR1 and ELAPOR2
Key inclusion criteria (2 listed)
- Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures.
- subjects with genetic variations in ELAPOR1 and ELAPOR2
Key exclusion criteria (4 listed)
- Women during pregnancy and lactation
- Treatment with any medication effecting on glucose metabolism like anti-diabetic drugs or steroids
- Any pancreatic disease
- Known current presence or history of severe neurological or psychiatric diseases, schizophrenia, bipolar disorder
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Insulin secretion capacity
Time frame: -15 minutes - 130 minutes
Glucose stimulated insulin secretion adjusted for insulin sensitivity during an hyperglycemic clamp in subjects with genetic variants in ELAPOR1 and ELAPOR2 compared to a control cohort without genetic variants.
1 secondary outcome
Glucose tolerance status
Time frame: 0-120 minutes
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2023.
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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.
Reiner Jumpertz-von Schwartzenberg, MD contact
Reiner Jumpertz-von Schwartzenberg, MD principal investigator
University Hopsital Tübingen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Type 2 Diabetes and Impaired Insulin Secretion, run by University Hospital Tuebingen at 1 site in Germany.
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 4 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: status not confirmed, as of the sponsor's last update on 25 Sep 2023. 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 Germany. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Reiner Jumpertz-von Schwartzenberg, MD (+49 7071 29 68934, Reiner.Jumpertz-vs@med.uni-tuebingen.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Insulin secretion capacity (time frame: -15 minutes - 130 minutes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 25 Sep 2023.