A pilot study to investigate the effect of pioglitazone on muscle and liver triglyceride content and total body fat in patients with familial combined hyperlipidaemia: relation to parameters of lipid and carbohydrate metabolism

ISRCTN	ISRCTN34596899
DOI	https://doi.org/10.1186/ISRCTN34596899
Secondary identifying numbers	N/A

Submission date: 29/07/2005
Registration date: 13/09/2005
Last edited: 25/04/2014

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Nutritional, Metabolic, Endocrine

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Rossi Naoumova
Scientific

MRC Clinical Sciences Centre
Hammersmith Hospital
Du Cane Road
London
W12 0NN
United Kingdom

Study information

Study design	Randomised controlled trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Not specified
Study type	Not Specified
Scientific title
Study objectives	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(s)	Research Ethics Committee approval No. 2002/6480
Health condition(s) or problem(s) studied	Familial Combined Hyperlipidaemia
Intervention	Treatment with pioglitazone versus placebo
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Not Specified
Drug / device / biological / vaccine name(s)	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 study start date	18/12/2002
Completion date	30/06/2006

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Upper age limit	75 Years
Sex	Both
Target number of participants	26
Key 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
Key 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.)
Date of first enrolment	18/12/2002
Date of final enrolment	30/06/2006

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

MRC Clinical Sciences Centre

London
W12 0NN
United Kingdom

Sponsor information

Medical Research Council (UK)
Research council

Clinical Sciences Centre
Hammersmith HospitalMedical
Du Cane Road
London
W12 0NN
United Kingdom

Website	http:\\www.mrc.ac.uk
"ROR"	https://ror.org/03x94j517

Funders

Funder type

Research council

Medical Research Council and J Coller Foundation (UK)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/11/2007		Yes	No