Abnormal Lipids - Causes and Effects

NCT02195050 | Recruiting

• 2 other identifiers: APOB2012R03301
• Study Type: observational
• Target: 1,396
• Locations: 1 country
• Sites: 1

Brief Summary

1. 1.At target LDL-C levels, apoB100 concentrations will be higher than recommended levels in the following populations:
2. 2.Tertiary centre lipid clinic patients with raised TG treated with statins.
3. 3.Patients with type 2 diabetes treated with statins.
4. 4.Patients with Chronic Kidney disease (CKD) stages 4 and 5 treated with statins.
5. 5.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.
6. 6.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.
7. 7.LAL deficiency is underdiagnosed in patients with severe hypertriglyceridaemia, low HDL-C, hyperlipidaemias, non alcoholic fatty liver disease and idiopathic high liver enzymes.

Conditions

Hypertriglyceridaemia

Outcome Measures

Primary Outcomes (1)

• 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.

  1 day.

Study Arms (3)

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.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients are recruited from secondary and tertiary care hospital clinics.

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Manchester University NHS Foundation Trust: lead

Study Sites (1)

Cardiovascular Trials Unit

Manchester, M13 9WL, United Kingdom

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Serum \& plasma samples will be stored for further studies.

MeSH Terms

Conditions

Hypertriglyceridemia

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Handrean Soran, MD FRCP

  Manchester University NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Central Study Contacts

See Kwok, MD FRCGP

CONTACT

01612768863; sk7@doctors.org.uk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2014
• First Posted: July 21, 2014
• Study Start: January 23, 2014
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 1, 2030
• Last Updated: May 31, 2023

Record last verified: 2023-05

Locations

GB (1)