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Trial record 1 of 2 for:    paraoxonase | United Kingdom
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Paraoxonase and HDL Qualities in Glycaemia and Inflammation (PON1)

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ClinicalTrials.gov Identifier: NCT02169518
Recruitment Status : Recruiting
First Posted : June 23, 2014
Last Update Posted : April 1, 2021
Sponsor:
Collaborators:
British Heart Foundation
Juvenile Diabetes Research Foundation
Information provided by (Responsible Party):
Manchester University NHS Foundation Trust

Brief Summary:

The incidence of coronary heart disease (CHD) is significant in the super-obese and diabetics.

Inflammation is believed to play an important part in the development of CHD, and the large collection of abdominal fat in the obese person is a vast source of inflammation. Diabetics have abnormal glucose and cholesterol metabolism which ultimately compromise their bodies' circulatory system and nerve function.

Cholesterol plays a vital role in CHD. Low-density lipoprotein (LDL) particles carry cholesterol and deposit it in blood vessel walls which become damaged as a result. When LDL particles undergo changes chemically (called oxidation) or as a result of high circulating blood glucose (called glycation), they become more harmful to the body. High-density lipoprotein (HDL) particles have a protective function in CHD. Not only do they transport cholesterol away from the blood vessels to the liver to be broken down, they have properties against oxidation and inflammation. These properties are related to the activity of an enzyme on HDL called paraoxonase 1(PON1).

Super-obese patients are increasingly treated by weight-reducing surgery (bariatric surgery). In this study we examine whether weight loss following bariatric surgery results in reduced inflammatory state, improved HDL function (higher PON1 activity), better control of blood glucose and less nerve damage.

We will study PON1 activity, inflammation and glucose control in patients with type 1 diabetes (with and without kidney damage) and type 2 diabetes. We will also study the effects of rapidly rising blood glucose levels on PON1 and glycated LDL in patients undergoing oral glucose tolerance test.


Condition or disease
Diabetes Mellitus Bariatric Surgery Candidate

Detailed Description:

High-density lipoprotein (HDL) is known to have a protective role in cardiovascular disease. Apart from transporting cholesterol from peripheral blood vessels back to the liver where it is processed, HDL has the ability to inhibit chemical changes (called oxidation) to low-density lipoprotein (LDL) which would make the latter more toxic to the body. HDL can also stop inflammatory particles from damaging the vessel walls. The anti-oxidation and anti-inflammatory properties of HDL are associated with an enzyme on HDL called paraoxonase 1 (PON1). It is not the level of measured HDL but the level of PON1 activity that is important in preventing cardiovascular disease. PON1 activity determines the quality of HDL and the effect against vascular disease.

Obese patients accumulate most of the fat within their abdomen (termed visceral fat). It is known that visceral fat produces large quantities of inflammatory particles so that obese patients have increased systemic inflammation and thus higher risk of vascular disease. The impact of heightened inflammatory status on HDL functions and PON1 activity is not known. Weight-reducing (bariatric) surgery can result in significant weight loss in obese patients. It is unclear whether the weight loss is associated with improvement in HDL functions, possible reversal of lipoprotein abnormalities and other physiological parameters. We plan to study a population of obese patients scheduled to have bariatric surgery before and after the surgery and compare the results with a matching population of healthy control patients.

Diabetic patients are at increased risk of developing cardiovascular disease. HDL in diabetic patients is often dysfunctional. Even though HDL levels are normal, PON1 activity may be reduced. LDL is able to interact with raised levels of blood glucose (called glycation) and become more harmful to the body. Glycation of lipoproteins associated with PON1 may affect PON1 activity. We plan to study glycated lipoproteins and PON1 activity in a population of diabetic patients who have either type 1 or type 2 diabetes. Some of the type 1 diabetics will have diabetic kidney disease, these patients are known to be particularly at high risk of cardiovascular complications. We also plan to recruit a cohort of patients who do not have diabetes but who have had an abnormal blood glucose test. These patients will be having an oral glucose tolerance test (OGTT) which establishes whether they have diabetes. During the OGTT, patients are given an oral glucose load which results in a rapid rise in blood glucose. We will see if this accelerated change in blood glucose level has any effects on the glycation of lipoproteins.

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Study Type : Observational
Estimated Enrollment : 600 participants
Observational Model: Case-Only
Time Perspective: Other
Official Title: Changes in Paraoxonase Activity, HDL Properties, Inflammatory Markers and Corneal Innervation in Post-bariatric Surgery Patients, Type 1 Diabetics With and Without Nephropathy, Type 2 Diabetics, and During an Oral Glucose Tolerance Test.
Actual Study Start Date : July 5, 2012
Estimated Primary Completion Date : February 2024
Estimated Study Completion Date : February 2024

Resource links provided by the National Library of Medicine


Group/Cohort
Diabetes Arm
Patients with Type 1 and Type 2 diabetes
Bariatric Arm
Obese patients scheduled for bariatric surgery



Primary Outcome Measures :
  1. Paraoxonase activity is measured using a semi-automated microtitre plate method. [ Time Frame: 1 day ]
    Paraoxonase activity is measured and analysed in the groups of patients with defined medical conditions according to the study protocol.



Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
60 patients with type 1 diabetes 60 control subjects for type 1 diabetics 60 patients with type 2 diabetes 60 control subjects for type 2 diabetics 60 patients undergoing oral glucose tolerance test 120 patients scheduled for bariatric surgery - lipoprotein group 120 control subjects for bariatric patients 60 patients scheduled for bariatric surgery - nerve function & structure group
Criteria

Inclusion Criteria:

  • Patients with Type 1 diabetes who are not receiving lipid-lowering drugs, omega fatty acid supplements or thiazolidinediones and without clinical and/or ECG evidence of CHD.

Type 2 diabetic patients who are not receiving omega fatty acid supplements or thiazolidinediones and without clinical and/or ECG evidence of CHD.

Patients with impaired fasting glucose undergoing oral glucose tolerance test. Patients scheduled for bariatric surgery. Healthy controls who have no major acute or chronic illness, are not receiving regular medication and not taking omega fatty acid supplements, do not have clinically overt ischaemic heart disease.

Subjects (male and female) aged between 20 and 75. Subjects who have capacity and understanding for informed consent process.

Exclusion Criteria:

  • Type 1 diabetics using lipid lowering therapy, thiazolidinediones, omega fatty acid supplements. History and/or ECG evidence of ST segment changes indicative of CHD.

Type 2 diabetics receiving thiazolidinediones, omega fatty acid supplements. History and/or ECG evidence of ST segment changes indicative of CHD.

Healthy controls who have any history of CHD, vascular insufficiency, or diabetes. Use of any lipid-lowering drug or omega fatty acid supplements.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02169518


Contacts
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Contact: Handrean Soran, MD FRCP 01612764843 hsoran@aol.com
Contact: See Kwok, MD FRCGP 01612768863 sk7@doctors.org.uk

Locations
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United Kingdom
Central Manchester University Hospitals NHS Foundatioon Trust Recruiting
Manchester, Lancashire, United Kingdom, M13 9WL
Contact: Jonathan Schofield, MRCP    07866529898    jschofield@doctors.org.uk   
Contact: See Kwok, MD FRCGP    01612768863    sk7@doctors.org.uk   
Principal Investigator: Handrean Soran, MD FRCP         
Sponsors and Collaborators
Manchester University NHS Foundation Trust
British Heart Foundation
Juvenile Diabetes Research Foundation
Investigators
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Principal Investigator: Handrean Soran, MD FRCP Manchester University NHS Foundation Trust
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Manchester University NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT02169518    
Other Study ID Numbers: PON2011
First Posted: June 23, 2014    Key Record Dates
Last Update Posted: April 1, 2021
Last Verified: March 2021
Keywords provided by Manchester University NHS Foundation Trust:
PON1 activity
HDL functionality
LDL oxidation
Diabetes Mellitus Type 1
Obesity
Diabetes Mellitus Type 2
Bariatric Surgery
Additional relevant MeSH terms:
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Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases