Condition category
Nutritional, Metabolic, Endocrine
Date applied
09/09/2005
Date assigned
27/10/2005
Last edited
07/12/2007
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Prof Paolo Camici

ORCID ID

Contact details

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

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

AD-4833 / EC414

Study information

Scientific title

Acronym

Study hypothesis

The disturbance of fat metabolism (utilisation) known as combined hyperlipidaemia (CHL) is very common and affects up to 2% of the population. Patients who suffer from this disorder have a 20% higher risk to develop obstructive disease of the blood vessels of the heart and heart attack.

The patients with CHL have abnormalities of blood lipids (fat) similar to those observed in patients who suffer from another condition known as the 'metabolic syndrome' who are also at higher risk of developing heart disease, stroke and diabetes. One of the features of this metabolic syndrome is a reduced response to the hormone insulin. This hormone helps the tissues of the body (in particular the muscles and the heart) to use sugar. Sugar is very important for the heart since it contributes to generate the energy which is used to sustain its function.

In patients with the metabolic syndrome insulin is less effective and the heart tissue has difficulties in using sugar and develops a condition known as 'insulin resistance'. Previous studies have shown that this condition of insulin resitance can contribute to the higher incidence of heart disease in patients with the metabolic syndrome.

Pioglitazone is a drug licenced in the UK which acts by sensitising the liver and peripheral tissues (including the heart) to the effect of insulin, which results in improved insulin-mediated sugar disposal. Previous studies have demonstrated that pioglitazone lowers sugar and insulin levels in the blood and improves lipid (fat) metabolism (utilisation) in patients with diabetes. We expect similar beneficial effects in patients with familial CHL treated with pioglitazone.

We therefore hypothesise that patients with CHL will have insulin resistance at the heart muscle level as well as an abnormal function of the vessels supplying blood to the heart and that treatment with pioglitazone will improve these

To prove our hypothesis we will use a special scan called Positron Emission Tomography (PET) which permits to measure the utilisation of sugar by the heart in a totally non-invasive fashion. PET is also capable of providing information on the function of the vessels supplying blood to the heart. Patients with familial CHL will be studied by means of PET before and after 4 months of treatment with pioglitazone. In addition, we will assess the effect of the drug on blood lipids (fat).

Ethics approval

Ethics approval received from the Hammersmith & Queen Charlotte's and Chelsea Hospitals Research Ethics Committee (ref: 2002/6373).

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Condition

Familial Combined Hyperlipidaemia

Intervention

Treatment with pioglitazone versus placebo

Intervention type

Drug

Phase

Not Specified

Drug names

Pioglitazone

Primary outcome measures

1. Whole body glucose uptake
2. Myocardial glucose uptake
3. Basal myocardial blood flow
4. Coronary vasodilator reserve

Secondary outcome measures

Parameters of lipid and carbohydrate metabolism.

Overall trial start date

01/05/2004

Overall trial end date

19/12/2006

Reason abandoned

Eligibility

Participant inclusion criteria

Patients must be/have:
1. Male or female aged between 30 and 70 years
2. Familial Combined Hyperlipidaemia (CHL) that fits the diagnostic criteria
3. Inadequately controlled with conventional lipid lowering medication, with at least one of
the following:
3.1. Total cholesterol more than 5.0 mmol/l
3.2. Triglyceride more than 1.7 mmol/l
3.3. High Density Lipoprotein (HDL) cholesterol less than 1.0 mmol/l
3.4. Total cholesterol: HDL-cholesterol ratio more than 5.0
4. On stable lipid lowering medication (dose and drug) for the previous two months
5. A Body Mass Index (BMI) of less than or equal to 35 kg/m^2
6. Willing and able to comply with the conditions and requirements of the study
7. 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

Patients must not be/have:
1. Had a myocardial infarction, stroke or transient ischaemic attack in the previous six months
2. Had malignant disease in the previous five years (except basal cell carcinoma)
3. Undergoing haemodialysis
4. Any of the following conditions:
4.1. Type one or type two diabetes mellitus
4.2. Chronic uncontrolled asthma
4.3. An inability to tolerate PET scanning
4.4. New York Heart Association (NYHA) class II, III or IV congestive heart failure
4.5. Alcohol or drug abuse
4.6. Significant renal impairment (defined as creatinine more than 135 µmol/l)
4.7. Abnormal liver tests (defined as alanine aminotransferase [ALT] more than 2.5 times the upper limit of the reference range)
4.8. Known Human Immunodeficiency Virus (HIV) infection or viral hepatitis
5. Had treatment with corticosteroids in the previous four weeks (use of topical or inhaled corticosteroids is allowed)
6. Taken another investigational study drug or product within the previous three months
7. Donated and/or received any blood or blood products within the previous three months
8. Female patients who are any of the following:
8.1. Pregnant, planning pregnancy during the study or breast feeding
8.2. Of child-bearing potential and not planning to use a reliable method of contraception throughout the study (e.g. intrauterine device [IUD] or oral contraception)
9. Any other condition or circumstance that in the opinion of the investigator may compromise the patient’s ability to comply with the study protocol

Recruitment start date

01/05/2004

Recruitment end date

19/12/2006

Locations

Countries of recruitment

United Kingdom

Trial participating centre

MRC Clinical Sciences Centre
London
W12 0NN
United Kingdom

Sponsor information

Organisation

Takeda Europe R and D Centre (UK)

Sponsor details

Savannah House
11-12 Charles II Street
London
SW1Y 4QU
United Kingdom

Sponsor type

Industry

Website

http://www.tgrd.com

Funders

Funder type

Industry

Funder name

Takeda Europe R and D Centre (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

Results - basic reporting

Publication summary

Results in http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=18021872

Publication citations

  1. Results

    Naoumova RP, Kindler H, Leccisotti L, Mongillo M, Khan MT, Neuwirth C, Seed M, Holvoet P, Betteridge J, Camici PG, Pioglitazone improves myocardial blood flow and glucose utilization in nondiabetic patients with combined hyperlipidemia: a randomized, double-blind, placebo-controlled study., J. Am. Coll. Cardiol., 2007, 50, 21, 2051-2058, doi: 10.1016/j.jacc.2007.07.070.

Additional files

Editorial Notes