Hypertriglyceridaemia - Cause and Effects
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|ClinicalTrials.gov Identifier: NCT02195050|
Recruitment Status : Recruiting
First Posted : July 21, 2014
Last Update Posted : December 19, 2018
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.
|Condition or disease|
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 Type :||Observational|
|Estimated Enrollment :||1396 participants|
|Official Title:||Hypertriglyceridaemia: Therapeutic Targets, Genetic Causes, and Associated Neuropathy|
|Actual Study Start Date :||January 23, 2014|
|Estimated Primary Completion Date :||December 2025|
|Estimated Study Completion Date :||December 2025|
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.
- 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.
Biospecimen Retention: Samples With DNA
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): NCT02195050
|Contact: See Kwok, MD FRCGPfirstname.lastname@example.org|
|Cardiovascular Trials Unit||Recruiting|
|Manchester, United Kingdom, M13 9WL|
|Contact: See Kwok, MD FRCGP 01612768863 email@example.com|
|Sub-Investigator: See Kwok, MD FRCGP|
|Principal Investigator:||Handrean Soran, MD FRCP||Manchester University NHS Foundation Trust|