Effect of Serum LDL Cholesterol Concentration on Pancreatic Insulin Secretion

Sponsor

University Hospital Tuebingen (Other)

Overall Status

Recruiting

CT.gov ID

NCT04314167

Collaborator

(none)

Enrollment

Location

Arm

34.6

Anticipated Duration (Months)

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief 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. 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.

Condition or Disease	Intervention/Treatment	Phase
Hypercholesterolemia Insulin Resistance Insulin Secretion	Drug: Lowering cholesterol concentrations by PCSK-9 inhibitor	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

Effect of Serum LDL Cholesterol Concentration on Pancreatic Insulin Secretion

Actual Study Start Date :

Jul 28, 2020

Anticipated Primary Completion Date :

Mar 15, 2023

Anticipated Study Completion Date :

Jun 15, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LDL lowering therapy Patients will receive the PCSK9-inhibitor Evolocumab as part of routine clinical management within the indication of this drug.	Drug: Lowering cholesterol concentrations by PCSK-9 inhibitor Patients will receive the PCSK9-inhibitor Evolocumab as part of routine clinical management within the indication of this drug.

Arm

Intervention/Treatment

Experimental: LDL lowering therapy

Patients will receive the PCSK9-inhibitor Evolocumab as part of routine clinical management within the indication of this drug.

Drug: Lowering cholesterol concentrations by PCSK-9 inhibitor

Patients will receive the PCSK9-inhibitor Evolocumab as part of routine clinical management within the indication of this drug.

Outcome Measures

Primary Outcome Measures

Change in insulin secretion. [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).

Secondary Outcome Measures

Change in insulin sensitivity. [before and after 12 weeks of treatment with a PCSK9-inhibitor.]
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).
Change in insulin clearance. [before and after 12 weeks of treatment with a PCSK9-inhibitor.]
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).
Change in glucose tolerance. [before and after 12 weeks of treatment with a PCSK9-inhibitor.]
Effect of lowering LDL cholesterol levels on glucose tolerance assessed by 75g oral glucose tolerance test

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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%

Exclusion Criteria:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Tuebingen, Department of Internal Medicine IV	Tuebingen		Germany	72076

Sponsors and Collaborators

University Hospital Tuebingen

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

University Hospital Tuebingen

ClinicalTrials.gov Identifier:

NCT04314167

Other Study ID Numbers:

045/2020BO2

First Posted:

Mar 19, 2020

Last Update Posted:

Aug 25, 2022

Last Verified:

Aug 1, 2022

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Insulin Resistance

Hypercholesterolemia

Study Results

No Results Posted as of Aug 25, 2022