Diabetes MellitusPON1NCT02169518
Paraoxonase and HDL Qualities in Glycaemia and Inflammation
An observational study of Diabetes Mellitus and Bariatric Surgery Candidate, run by Manchester University NHS Foundation Trust at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Diabetes Mellitus, Bariatric Surgery Candidate
- How many people
- 600 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 5 Jul 2012to 31 Jan 2030
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 20 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
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
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United Kingdom1 site, 1 recruiting
- Recruiting
Central Manchester University Hospitals NHS Foundatioon Trust
Manchester, Lancashire, M13 9WL
Jonathan Schofield, MRCP, 07866529898, jschofield@doctors.org.uk
See Kwok, MD FRCGP, 01612768863, sk7@doctors.org.uk
About this study
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.
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.
Read more
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.
Read the 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.
- Conditions
- Diabetes Mellitus, Bariatric Surgery Candidate
- Keywords
- PON1 activity, HDL functionality, LDL oxidation, Diabetes Mellitus Type 1, Obesity, Diabetes Mellitus Type 2, Bariatric Surgery
- Medical subject headings
- Diabetes Mellitus, Diabetes Mellitus, Type 1, Obesity, 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 |
|---|---|---|
| Diabetes Arm | Patients with Type 1 and Type 2 diabetes | |
| Bariatric Arm | Obese patients scheduled for bariatric surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
Paraoxonase activity is measured using a semi-automated microtitre plate method.
Paraoxonase activity is measured and analysed in the groups of patients with defined medical conditions according to the study protocol.
Measured: 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2014 (estimated)
- Study start5 Jul 2012
- Primary completion31 Jan 2030 (estimated)
- Study completion31 Jan 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diabetes MellitusStudies of the same condition, open and under way.
- 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
- Case only
- Time perspective
- Other
- Enrolment
- 600 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Manchester University NHS Foundation Trust
- Sponsor type
- Other government
- Collaborators
- British Heart Foundation, Juvenile Diabetes Research Foundation
- Responsible party
- Sponsor
- Investigators
- Handrean Soran, MD FRCP, Principal investigator, Manchester University NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02169518
- Sponsor's protocol ID
- PON2011
- Acronym
- PON1
- Status last verified
- Apr 2023
- First submitted
- 19 Jun 2014
- Last updated
- 12 Apr 2023
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Yadav R, Hama S, Liu Y, Siahmansur T, Schofield J, Syed AA, France M, Pemberton P, Adam S, Ho JH, Aghamohammadzadeh R, Dhage S, Donn R, Malik RA, New JP, Jeziorska M, Durrington P, Ammori BA, Soran H. Effect of Roux-en-Y Bariatric Surgery on Lipoproteins, Insulin Resistance, and Systemic and Vascular Inflammation in Obesity and Diabetes. Front Immunol. 2017 Nov 15;8:1512. doi: 10.3389/fimmu.2017.01512. eCollection 2017.
PubMed 29187850
Study at a glance
From the registry record, last updated by the sponsor on 12 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT02169518
- Acronym / sponsor ID
- PON1 / PON2011
- Conditions
- Diabetes Mellitus, Bariatric Surgery Candidate
- Keywords
- PON1 activity, HDL functionality, LDL oxidation, Diabetes Mellitus Type 1, Obesity, Diabetes Mellitus Type 2, Bariatric Surgery
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 600 participants (estimated)
- Lead sponsor
- Manchester University NHS Foundation TrustOther government
- Collaborators
- British Heart Foundation, Juvenile Diabetes Research Foundation
- Study start
- 5 Jul 2012 (actual)
- Primary completion
- 31 Jan 2030 (estimated)
- Study completion
- 31 Jan 2030 (estimated)
- First posted
- 23 Jun 2014 (estimated)
- 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.
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.
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.
Study design
- Observational model
- Case only
- Time perspective
- Other
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Diabetes Arm | – | –Patients with Type 1 and Type 2 diabetes |
| Bariatric Arm | – | –Obese patients scheduled for bariatric surgery |
Who may qualify
- Ages
- 20 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- 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
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (3 listed)
- 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.
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
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Apr 2023.
- Derived from this study: PubMed 29187850Yadav R, Hama S, Liu Y, Siahmansur T, Schofield J, Syed AA, France M, Pemberton P, Adam S, Ho JH, Aghamohammadzadeh R, Dhage S, Donn R, Malik RA, New JP, Jeziorska M, Durrington P, Ammori BA, Soran H. Effect of Roux-en-Y Bariatric Surgery on Lipoproteins, Insulin Resistance, and Systemic and Vascular Inflammation in Obesity and Diabetes. Front Immunol. 2017 Nov 15;8:1512. doi: 10.3389/fimmu.2017.01512. eCollection 2017.
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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.
Handrean Soran, MD FRCP principal investigator
Manchester University NHS Foundation Trust
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 Diabetes Mellitus and Bariatric Surgery Candidate, run by Manchester University NHS Foundation Trust at 1 site in United Kingdom.
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 4 inclusion and 3 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: looking for participants now, as of the sponsor's last update on 12 Apr 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 United Kingdom. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Handrean Soran, MD FRCP (01612764843, hsoran@aol.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Paraoxonase activity is measured using a semi-automated microtitre plate method. (time frame: 1 day). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02169518, which also lists 1 linked publication.
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 12 Apr 2023.