Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
N/A
Study information
Scientific title
Acronym
Study hypothesis
We hypothesise that patients with familial combined hyperlipidaemia will have increased skeletal muscle and liver triglyceride content as well as visceral obesity. Treatment with pioglitazone will improve these abnormalities and the lipid profile as a result of increased insulin sensitivity through its action on the PPAR gamma-receptor.
Ethics approval
Research Ethics Committee approval No. 2002/6480
Study design
Randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Not Specified
Patient information sheet
Condition
Familial Combined Hyperlipidaemia
Intervention
Treatment with pioglitazone versus placebo
Intervention type
Drug
Phase
Not Specified
Drug names
Pioglitazone
Primary outcome measure
Skeletal muscle and liver triglyceride content, using 1H Magnetic Resonance Spectroscopy (1H-MRS) and total body fat map: visceral, non-visceral and subcutaneous, using Magnetic Resonance Imaging (MRI)
Secondary outcome measures
Parameters of lipid and carbohydrate metabolism: Total cholesterol, triglyceride, HDL cholesterol, LDL cholesterol, total to HDL cholesterol ratio, Non-Esterified Fatty Acids (NEFA), Lipoprotein a (Lp(a)), apolipoprotein A-I, apolipoprotein B, glucose, insulin, leptin
Overall trial start date
18/12/2002
Overall trial end date
30/06/2006
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Age between 18-75 years
2. Familial combined hyperlipidaemia (CHL) that fits the above criteria
3. Inadequately controlled with conventional lipid lowering medication, with at least one of the following: total cholesterol >5.0 mmol/l; triglyceride >1.7 mmol/l; HDL-cholesterol <1.0 mmol/l; total cholesterol:HDL cholesterol ratio >5.0
4. Willing and able to comply with the conditions and requirements of the study
5. Signed and dated an informed consent form and be able to comply with the study procedures
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
26
Participant exclusion criteria
1. Hyperlipidaemia at diagnosis, secondary to obesity, diabetes mellitus, hypothyroidism, liver or kidney disease
2. Taking medication affecting serum lipids or excessive alcohol intake
3. Other forms of genetic hyperlipidaemia (familial hypercholesterolaemia)
4. Pregnancy
5. MI ('heart attack'), stroke or transient ischaemic attack ('mini stroke') in the previous 6 months
6. Malignant disease (cancer) in the previous 5 years (except basal cell carcinoma)
7. Type 1 or type 2 diabetes mellitus
8. NYHA class II, III or IV (mild, moderate or severe Heart Failure)
9. Alcohol or drug abuse
10. Significant renal (kidney) impairment (creatinine >135 µmol/l)
11. Abnormal liver tests (alanine aminotransferase [ALT] >2.5 times the upper limit of the reference range)
12.Had any alteration in their lipid lowering medication (dose or drug) in the previous 2 months
13. Had treatment with corticosteroids ('cortisol') in the previous 4 weeks (use of topical or inhaled corticosteroids is allowed)
14. Taken another investigational study drug or product within the previous 3 months
15. Donated or received blood or blood products within the previous 3 months
16. Females who are any of the following: Planning pregnancy during the study or breast feeding, or child bearing potential and not planning to use a reliable method of contraception throughout the study (e.g. oral contraception)
17. Any other condition or circumstance that, in the opinion of the investigator, may compromise the patient's ability to comply with the study protocol
18. An inability to tolerate MRI/MRS scanning (claustrophobia)
19. Standard contraindications for MRI/MRS scanning (e.g. cardiac pacemaker, mechanical heart valve, history of foreign body in the eye, IUCD, haemostatic clips, metal prosthesis, orthopaedic plates, occupation as metal worker, welder etc.)
Recruitment start date
18/12/2002
Recruitment end date
30/06/2006
Locations
Countries of recruitment
United Kingdom
Trial participating centre
MRC Clinical Sciences Centre
London
W12 0NN
United Kingdom
Sponsor information
Organisation
Medical Research Council (UK)
Sponsor details
Clinical Sciences Centre
Hammersmith HospitalMedical
Du Cane Road
London
W12 0NN
United Kingdom
Sponsor type
Research council
Website
Funders
Funder type
Research council
Funder name
Medical Research Council and J Coller Foundation (UK)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
2007 results in: http://www.ncbi.nlm.nih.gov/pubmed/17482623
Publication citations
-
Results
Thomas EL, Potter E, Tosi I, Fitzpatrick J, Hamilton G, Amber V, Hughes R, North C, Holvoet P, Seed M, Betteridge DJ, Bell JD, Naoumova RP, Pioglitazone added to conventional lipid-lowering treatment in familial combined hyperlipidaemia improves parameters of metabolic control: relation to liver, muscle and regional body fat content., Atherosclerosis, 2007, 195, 1, e181-90, doi: 10.1016/j.atherosclerosis.2007.03.043.