HypertriglyceridaemiaNCT02195050
Abnormal Lipids - Causes and Effects
An observational study of Hypertriglyceridaemia, run by Manchester University NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
1. At target LDL-C levels, apoB100 concentrations will be higher than recommended levels in the following populations: 1. Tertiary centre lipid clinic patients with raised TG treated with statins. 2. Patients with type 2 diabetes treated with statins. 3. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hypertriglyceridaemia
- How many people
- 1,396 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 23 Jan 2014to Dec 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients are recruited from secondary and tertiary care hospital clinics.
Who may be able to join
- Therapeutic target arm
- Statin treated patients with and without hypertriglyceridemia.
- Statin treated patients with type 2 diabetes.
- Statin treated patients with CKD stages 4 and 5.
- Nerve function arm
- •Patients known to have severe hypertriglyceridaemia (defined as triglyceride >5.5 mmol/l) but not known to have diabetes and matched controls.
Show all 9Show fewer
- Genetic screening arm
- Patients with a documented triglyceride level of more than 10 mmol/l at any time.
- Criteria for screening for FH and LAL deficiency include non-obese patients (BMI <30) with low HDL-C (<1.0 mmol/l male and <1.3 mmol female), high triglycerides >1.7 mmol/l, high total cholesterol >6.2 or LDL cholesterol >4.7 mmol/l; patients with raised liver alanine aminotransferase (ALT) (1.5 x above ULN) but no metabolic or viral disease or alcohol excess and patients diagnosed with NAFLD with or without hyperlipidaemia.
Who cannot join
- Pregnant and/or breast-feeding women.
- Significant liver impairment.
- Patients known to have active malignant disease.
- Patients treated with medications that could affect lipoprotein metabolism significantly (like atypical antipsychotics, chemotherapy).
- Untreated hypothyroid and hyperthyroidism (if treated and TFT normal could be recruited).
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
Cardiovascular Trials Unit
Manchester, M13 9WL
See Kwok, MD FRCGP, 01612768863, sk7@doctors.org.uk
See Kwok, MD FRCGP
About this study
Official title: Hypertriglyceridaemia: Therapeutic Targets, Genetic Causes, and Associated Neuropathy
- At target LDL-C levels, apoB100 concentrations will be higher than recommended levels in the following populations:
- Tertiary centre lipid clinic patients with raised TG treated with statins.
- Patients with type 2 diabetes treated with statins.
- Patients with Chronic Kidney disease (CKD) stages 4 and 5 treated with statins.
- Despite achieving LDL-C and non-HDL-C targets, a significant number of statin-treated patients have residual cardiovascular risk related to raised hsCRP. The relationship between hsCRP and Lp-PLA2 (markers of inflammation) and LDL particle number measured by apoB100 is stronger than that of measured and calculated LDL and non-HDL. In statin treated patients there will be higher levels of hs-CRP and Lp-PLA2 in patients achieving LDL targets but not apo B targets.
- We hypothesise that non-diabetic patients with severe hypertriglyceridaemia (fasting serum triglyceride >5.5 mmol/l) have evidence of greater nerve damage compared with matched controls.
- LAL deficiency is underdiagnosed in patients with severe hypertriglyceridaemia, low HDL-C, hyperlipidaemias, non alcoholic fatty liver disease and idiopathic high liver enzymes.
Read the detailed description
Fats are present in the body in the form of lipid particles containing cholesterol and triglycerides. Lipid particles can deposit in blood vessels, forming atheromas, blocking blood vessels and leading to heart attacks and strokes. These harmful particles are termed 'atherogenic' particles. Low density lipoprotein (LDL) is the major atherogenic particle. Each atherogenic particle has a protein associated with it called apolipoprotein B (apoB). Cholesterol, triglycerides, and apoB levels can be measured in the laboratory. In this study we focus on patients with raised levels of triglycerides (hypertriglyceridaemia).
We will recruit patients with hypertriglyceridaemia to look at (1) therapeutic targets, (2) genetic causes, and (3) associated neuropathy in these patients.
- Therapeutic target arm: LDL-cholesterol (LDL-C) is the primary target for lipid-lowering drugs. A drug (commonly a statin) is effective when it lowers LDL-C. Patients with diabetes, chronic kidney disease and hypertriglyceridaemia on statins may have normal levels of LDL-C; but because the size of LDL particles in these patients is smaller, they may in fact have raised levels of apoB and therefore remain at cardiovascular risk. Thus, measurement of apoB may be a better target for treatment because it measures 'atherogenic' particle numbers. Since atheromatous disease is an inflammatory disease, we will also investigate if residual risk may be correlated with inflammatory markers, such as hsCRP and Lp-PLA2.
- Hypertriglyceridaemia and nerve function arm: We aim to demonstrate that severe hypertriglyceridaemia is associated with more significant nerve damage.
- Genetic screening arm:
Several genetic mutations have been identified to cause hypertriglyceridaemia. Deficiency of the enzyme lysosomal acid lipase (LAL) results in Cholesterol Ester Storage Disease (CESD) and hypercholesterolaemia, hypertriglyceridaemia, and abnormal lipid deposition in organs. We wish to identify genetic mutations associated with severe hypertriglyceridemia and the prevalence of LAL deficiency in patients attending our tertiary referral centre.
- Conditions
- Hypertriglyceridaemia
- Medical subject headings
- Hypertriglyceridemia
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 |
|---|---|---|
| Therapeutic target arm | Statin treated patients with and without raised triglycerides who do not have diabetes or dysglycemia. Statin treated patients with type 2 diabetes.Statin treated patients with CKD stages 4 and 5 (eGFR ≤30mL/min). | |
| Nerve function arm | Patients with severe hypertriglyceridaemia (fasting TG > 5.5mmol/l.) are recruited for nerve function assessment and corneal confocal microscopy. | |
| Genetic screening arm | For LAL deficiency screening, patients will be recruited over a 5 year period with a documented triglyceride level of more than 10 mmol/l at any time, low HDLC, raised ALT, combined hyperlipidaemia, or non-alcoholic fatty liver disease. Patients recruited from Manchester will be offered additional genetic testing for familial hypercholesterolaemia. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Measurement of ApoB in specified patient populations to gauge cardiovascular risk.
Residual risk due to the presence of sd-LDL and reflected in a discrepancy between apoB and cholesterol indices is correlated with hs-CRP.
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 posted21 Jul 2014 (estimated)
- Study start23 Jan 2014
- Primary completionDec 2030 (estimated)
- Study completionDec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HypertriglyceridaemiaStudies 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
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 1,396 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Manchester University NHS Foundation Trust
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Handrean Soran, MD FRCP, Principal investigator, Manchester University NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02195050
- Sponsor's protocol ID
- APOB2012
- Other IDs
- R03301
- Status last verified
- May 2023
- First submitted
- 10 Jul 2014
- Last updated
- 31 May 2023
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hypertriglyceridaemia: Therapeutic Targets, Genetic Causes, and Associated Neuropathy
- ClinicalTrials.gov ID
- NCT02195050
- Acronym / sponsor ID
- APOB2012
- Conditions
- Hypertriglyceridaemia
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 1,396 participants (estimated)
- Lead sponsor
- Manchester University NHS Foundation TrustOther government
- Study start
- 23 Jan 2014 (actual)
- Primary completion
- Dec 2030 (estimated)
- Study completion
- Dec 2030 (estimated)
- First posted
- 21 Jul 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.
- At target LDL-C levels, apoB100 concentrations will be higher than recommended levels in the following populations:
- Tertiary centre lipid clinic patients with raised TG treated with statins.
- Patients with type 2 diabetes treated with statins.
- Patients with Chronic Kidney disease (CKD) stages 4 and 5 treated with statins.
- Despite achieving LDL-C and non-HDL-C targets, a significant number of statin-treated patients have residual cardiovascular risk related to raised hsCRP. The relationship between hsCRP and Lp-PLA2 (markers of inflammation) and LDL particle number measured by apoB100 is stronger than that of measured and calculated LDL and non-HDL. In statin treated patients there will be higher levels of hs-CRP and Lp-PLA2 in patients achieving LDL targets but not apo B targets.
- We hypothesise that non-diabetic patients with severe hypertriglyceridaemia (fasting serum triglyceride >5.5 mmol/l) have evidence of greater nerve damage compared with matched controls.
- LAL deficiency is underdiagnosed in patients with severe hypertriglyceridaemia, low HDL-C, hyperlipidaemias, non alcoholic fatty liver disease and idiopathic high liver enzymes.
Detailed description
Fats are present in the body in the form of lipid particles containing cholesterol and triglycerides. Lipid particles can deposit in blood vessels, forming atheromas, blocking blood vessels and leading to heart attacks and strokes. These harmful particles are termed 'atherogenic' particles. Low density lipoprotein (LDL) is the major atherogenic particle. Each atherogenic particle has a protein associated with it called apolipoprotein B (apoB). Cholesterol, triglycerides, and apoB levels can be measured in the laboratory. In this study we focus on patients with raised levels of triglycerides (hypertriglyceridaemia).
We will recruit patients with hypertriglyceridaemia to look at (1) therapeutic targets, (2) genetic causes, and (3) associated neuropathy in these patients.
- Therapeutic target arm: LDL-cholesterol (LDL-C) is the primary target for lipid-lowering drugs. A drug (commonly a statin) is effective when it lowers LDL-C. Patients with diabetes, chronic kidney disease and hypertriglyceridaemia on statins may have normal levels of LDL-C; but because the size of LDL particles in these patients is smaller, they may in fact have raised levels of apoB and therefore remain at cardiovascular risk. Thus, measurement of apoB may be a better target for treatment because it measures 'atherogenic' particle numbers. Since atheromatous disease is an inflammatory disease, we will also investigate if residual risk may be correlated with inflammatory markers, such as hsCRP and Lp-PLA2.
- Hypertriglyceridaemia and nerve function arm: We aim to demonstrate that severe hypertriglyceridaemia is associated with more significant nerve damage.
- Genetic screening arm:
Several genetic mutations have been identified to cause hypertriglyceridaemia. Deficiency of the enzyme lysosomal acid lipase (LAL) results in Cholesterol Ester Storage Disease (CESD) and hypercholesterolaemia, hypertriglyceridaemia, and abnormal lipid deposition in organs. We wish to identify genetic mutations associated with severe hypertriglyceridemia and the prevalence of LAL deficiency in patients attending our tertiary referral centre.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Therapeutic target arm | – | –Statin treated patients with and without raised triglycerides who do not have diabetes or dysglycemia. Statin treated patients with type 2 diabetes.Statin treated patients with CKD stages 4 and 5 (eGFR ≤30mL/min). |
| Nerve function arm | – | –Patients with severe hypertriglyceridaemia (fasting TG > 5.5mmol/l.) are recruited for nerve function assessment and corneal confocal microscopy. |
| Genetic screening arm | – | –For LAL deficiency screening, patients will be recruited over a 5 year period with a documented triglyceride level of more than 10 mmol/l at any time, low HDLC, raised ALT, combined hyperlipidaemia, or non-alcoholic fatty liver disease. Patients recruited from Manchester will be offered additional genetic testing for familial hypercholesterolaemia. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients are recruited from secondary and tertiary care hospital clinics.
Key inclusion criteria (9 listed)
- Therapeutic target arm
- Nerve function arm
- •Patients known to have severe hypertriglyceridaemia (defined as triglyceride >5.5 mmol/l) but not known to have diabetes and matched controls.
- Genetic screening arm
Key exclusion criteria (5 listed)
- Pregnant and/or breast-feeding women.
- Significant liver impairment.
- Patients known to have active malignant disease.
- Patients treated with medications that could affect lipoprotein metabolism significantly (like atypical antipsychotics, chemotherapy).
- Untreated hypothyroid and hyperthyroidism (if treated and TFT normal could be recruited).
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
Measurement of ApoB in specified patient populations to gauge cardiovascular risk.
Time frame: 1 day.
Residual risk due to the presence of sd-LDL and reflected in a discrepancy between apoB and cholesterol indices is correlated with hs-CRP.
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 31 May 2023.
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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 Hypertriglyceridaemia, 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 9 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: looking for participants now, as of the sponsor's last update on 31 May 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 See Kwok, MD FRCGP (01612768863, sk7@doctors.org.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Measurement of ApoB in specified patient populations to gauge cardiovascular risk. (time frame: 1 day.). 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 31 May 2023.