Effect of Serum LDL Cholesterol Concentration on Pancreatic Insulin Secretion

NCT04314167 | Terminated

• 1 other identifier: 045/2020BO2
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

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.

Conditions

Hypercholesterolemia; Insulin Resistance; Insulin Secretion

Outcome Measures

Primary Outcomes (1)

• 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).

  before and after 12 weeks of treatment with a PCSK9-inhibitor.

Secondary Outcomes (3)

• Change in insulin sensitivity.

  before and after 12 weeks of treatment with a PCSK9-inhibitor.

• Change in insulin clearance.

  before and after 12 weeks of treatment with a PCSK9-inhibitor.

• Change in glucose tolerance.

  before and after 12 weeks of treatment with a PCSK9-inhibitor.

Study Arms (1)

LDL lowering therapy

EXPERIMENTAL

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

Interventions

Lowering cholesterol concentrations by PCSK-9 inhibitor DRUG

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

LDL lowering therapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital Tuebingen: lead

Study Sites (1)

University of Tuebingen, Department of Internal Medicine IV

Tübingen, 72076, Germany

Location

MeSH Terms

Conditions

Hypercholesterolemia; Insulin Resistance

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Hyperinsulinism; Glucose Metabolism Disorders

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 10, 2020
• First Posted: March 19, 2020
• Study Start: July 28, 2020
• Primary Completion: March 1, 2024
• Study Completion: March 1, 2024
• Last Updated: May 16, 2024

Record last verified: 2024-05

Locations

DE (1)