HypercholesterolemiaNCT04314167
Effect of Serum LDL Cholesterol Concentration on Pancreatic Insulin Secretion
A study testing Lowering cholesterol concentrations by PCSK-9 inhibitor in people with Hypercholesterolemia and Insulin Resistance, run by University Hospital Tuebingen at 1 site in Germany.
Trial summary
Dyslipidemia is characterized by low levels of HDLs, hypertriglyceridemia as well as an increases proportion of small dense LDLs. Changes in lipoprotein particles and its concentrations, especially increased levels of pro-atherogenic LDL particles play an important role in the development of cardiovascular diseases. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Hypercholesterolemia, Insulin Resistance, Insulin Secretion
- What is being tested?
- Lowering cholesterol concentrations by PCSK-9 inhibitor
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteGermany
- Study dates
- 28 Jul 2020to 1 Mar 2024
- Phase
- Interventional
- 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
Who may be able to join
- Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures
- Medical indication for the treatment with a PCSK9-inhibitor
- HbA1c < 6,5%
Who cannot join
- Diabetes mellitus
- Pregnant women or breastfeeding
- Hb < 11.5 g/dl (males) or Hb < 10.5 g/dl (females)
- treatment with any medication that effects on blood glucose concentrations, e.g. antidiabetic drugs or steroids
- Any pancreatic disease
Trial locations and contacts
1 site in 1 country.
Germany1 site
University of Tuebingen, Department of Internal Medicine IV
Tübingen, 72076
About this study
Dyslipidemia is characterized by low levels of HDLs, hypertriglyceridemia as well as an increases proportion of small dense LDLs. Changes in lipoprotein particles and its concentrations, especially increased levels of pro-atherogenic LDL particles play an important role in the development of cardiovascular diseases. It is well established that statin/PCSK9-inhibitor treatment is very effective in lowering LDL cholesterol levels and therefore in preventing cardiovascular events. Besides the beneficial effects on cardiovascular system, these therapies are unfortunately linked to increased risk for type 2 diabetes.
However underlying mechanisms for the association between LDL cholesterol levels and the risk for type 2 diabetes remains largely unknown.Type 2 diabetes is especially characterized by insulin resistance and impaired insulin secretion from pancreatic beta-cells. Insulin resistance alone is insufficient to cause type 2 diabetes, as long as the ß-cell is able to compensate for the increased demand for insulin. Once this compensatory mechanism reaches its physiological limits, individuals progress to type 2 diabetes. Accordingly we aimed to investigate the associations between LDL cholesterol concentrations and the key issue in the pathogenesis of type 2 diabetes, insulin secretion before and after lowering cholesterol concentration by treatment with Evolocumab for 12 weeks in patients with medical indication for a treatment with a PCSK9-inhibitor. Therefore, patients will either undergo a hyperglycemic clamp or a oral glucose tolerance test in randomized manner.
- Conditions
- Hypercholesterolemia, Insulin Resistance, Insulin Secretion
- Being tested
- Lowering cholesterol concentrations by PCSK-9 inhibitor
- Medical subject headings
- Hypercholesterolemia, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lowering cholesterol concentrations by PCSK-9 inhibitorDrug
Patients will receive the PCSK9-inhibitor Evolocumab as part of routine clinical management within the indication of this drug.
| Study group | Role | What they receive |
|---|---|---|
| LDL lowering therapy | Experimental | Patients will receive the PCSK9-inhibitor Evolocumab as part of routine clinical management within the indication of this drug. Receives: Drug: Lowering cholesterol concentrations by PCSK-9 inhibitor |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in insulin secretion.
Effect of lowering LDL cholesterol levels on insulins secretion.This will be quantified in half of the patients by a hyperglycemic clamp and in the other half by a 75 g oral glucose tolerance test (randomized assignment).
Measured: before and after 12 weeks of treatment with a PCSK9-inhibitor.
Secondary outcomes (3)
Change in insulin sensitivity.
Effect of lowering LDL cholesterol levels on insulin sensitivity. This will be quantified in half of the patients by a hyperglycemic clamp and in the other half by a 75 g oral glucose tolerance test (randomized assignment).
Measured: before and after 12 weeks of treatment with a PCSK9-inhibitor.
Change in insulin clearance.
Effect of of lowering LDL cholesterol levels on insulin clearance.This will be quantified in half of the patients by a hyperglycemic clamp and in the other half by a 75 g oral glucose tolerance test (randomized assignment).
Measured: before and after 12 weeks of treatment with a PCSK9-inhibitor.
Change in glucose tolerance.
Effect of lowering LDL cholesterol levels on glucose tolerance assessed by 75g oral glucose tolerance test
Measured: before and after 12 weeks of treatment with a PCSK9-inhibitor.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2020
- Study start28 Jul 2020
- Primary completion1 Mar 2024
- Study completion1 Mar 2024
Why it stopped: poor recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HypercholesterolemiaStudies 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Tuebingen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04314167
- Sponsor's protocol ID
- 045/2020BO2
- Status last verified
- May 2024
- First submitted
- 10 Mar 2020
- Last updated
- 16 May 2024
- 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 16 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Serum LDL Cholesterol Concentration on Pancreatic Insulin Secretion
- ClinicalTrials.gov ID
- NCT04314167
- Acronym / sponsor ID
- 045/2020BO2
- Conditions
- Hypercholesterolemia, Insulin Resistance, Insulin Secretion
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: poor recruitment
- Enrolment
- 9 participants (actual)
- Lead sponsor
- University Hospital TuebingenUniversity, hospital or other
- Study start
- 28 Jul 2020 (actual)
- Primary completion
- 1 Mar 2024 (actual)
- Study completion
- 1 Mar 2024 (actual)
- First posted
- 19 Mar 2020 (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.
Dyslipidemia is characterized by low levels of HDLs, hypertriglyceridemia as well as an increases proportion of small dense LDLs. Changes in lipoprotein particles and its concentrations, especially increased levels of pro-atherogenic LDL particles play an important role in the development of cardiovascular diseases. It is well established that statin/PCSK9-inhibitor treatment is very effective in lowering LDL cholesterol levels and therefore in preventing cardiovascular events. Besides the beneficial effects on cardiovascular system, these therapies are unfortunately linked to increased risk for type 2 diabetes.
However underlying mechanisms for the association between LDL cholesterol levels and the risk for type 2 diabetes remains largely unknown.Type 2 diabetes is especially characterized by insulin resistance and impaired insulin secretion from pancreatic beta-cells. Insulin resistance alone is insufficient to cause type 2 diabetes, as long as the ß-cell is able to compensate for the increased demand for insulin. Once this compensatory mechanism reaches its physiological limits, individuals progress to type 2 diabetes. Accordingly we aimed to investigate the associations between LDL cholesterol concentrations and the key issue in the pathogenesis of type 2 diabetes, insulin secretion before and after lowering cholesterol concentration by treatment with Evolocumab for 12 weeks in patients with medical indication for a treatment with a PCSK9-inhibitor. Therefore, patients will either undergo a hyperglycemic clamp or a oral glucose tolerance test in randomized manner.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| LDL lowering therapy | Experimental | Drug: Lowering cholesterol concentrations by PCSK-9 inhibitorPatients will receive the PCSK9-inhibitor Evolocumab as part of routine clinical management within the indication of this drug. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures
- Medical indication for the treatment with a PCSK9-inhibitor
- HbA1c < 6,5%
Key exclusion criteria (5 listed)
- Diabetes mellitus
- Pregnant women or breastfeeding
- Hb < 11.5 g/dl (males) or Hb < 10.5 g/dl (females)
- treatment with any medication that effects on blood glucose concentrations, e.g. antidiabetic drugs or steroids
- Any pancreatic disease
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 |
|---|---|---|
| Lowering cholesterol concentrations by PCSK-9 inhibitorPatients will receive the PCSK9-inhibitor Evolocumab as part of routine clinical management within the indication of this drug. | Drug | LDL lowering therapy |
Primary outcome
Change in insulin secretion.
Time frame: before and after 12 weeks of treatment with a PCSK9-inhibitor.
Effect of lowering LDL cholesterol levels on insulins secretion.This will be quantified in half of the patients by a hyperglycemic clamp and in the other half by a 75 g oral glucose tolerance test (randomized assignment).
3 secondary outcomes
Change in insulin sensitivity.
Time frame: before and after 12 weeks of treatment with a PCSK9-inhibitor.
Change in insulin clearance.
Time frame: before and after 12 weeks of treatment with a PCSK9-inhibitor.
Change in glucose tolerance.
Time frame: before and after 12 weeks of treatment with a PCSK9-inhibitor.
Results and safety
The study was stopped early (reason given: poor recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2024.
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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 study testing Lowering cholesterol concentrations by PCSK-9 inhibitor in people with Hypercholesterolemia and Insulin Resistance, 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 3 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: stopped early, as of the sponsor's last update on 16 May 2024. 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?
The study was stopped early (reason given: poor recruitment). Results are not available in the source record.
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?
Change in insulin secretion. (time frame: before and after 12 weeks of treatment with a PCSK9-inhibitor.). 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 16 May 2024.