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Trial record 17 of 809 for:    APOB

Hypertriglyceridaemia - Cause and Effects

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02195050
Recruitment Status : Recruiting
First Posted : July 21, 2014
Last Update Posted : December 19, 2018
Information provided by (Responsible Party):
Manchester University NHS Foundation Trust

Brief 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. Patients with Chronic Kidney disease (CKD) stages 4 and 5 treated with statins.
  2. 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.
  3. 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.
  4. 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

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.

  1. 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.

  2. Hypertriglyceridaemia and nerve function arm:

    We aim to demonstrate that severe hypertriglyceridaemia is associated with more significant nerve damage.

  3. 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.

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Study Type : Observational
Estimated Enrollment : 1396 participants
Observational Model: Cohort
Time Perspective: Cross-Sectional
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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Triglycerides

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.

Primary Outcome Measures :
  1. 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
Serum & plasma samples will be stored for further studies.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients are recruited from secondary and tertiary care hospital clinics.

Inclusion Criteria:

  • 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.

  • 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.

Exclusion Criteria:

  • 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).

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 identifier (NCT number): NCT02195050

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Contact: See Kwok, MD FRCGP 01612768863

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United Kingdom
Cardiovascular Trials Unit Recruiting
Manchester, United Kingdom, M13 9WL
Contact: See Kwok, MD FRCGP    01612768863   
Sub-Investigator: See Kwok, MD FRCGP         
Sponsors and Collaborators
Manchester University NHS Foundation Trust
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Principal Investigator: Handrean Soran, MD FRCP Manchester University NHS Foundation Trust

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Responsible Party: Manchester University NHS Foundation Trust Identifier: NCT02195050     History of Changes
Other Study ID Numbers: APOB2012
First Posted: July 21, 2014    Key Record Dates
Last Update Posted: December 19, 2018
Last Verified: December 2018
Additional relevant MeSH terms:
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Lipid Metabolism Disorders
Metabolic Diseases