Abdominal Obesity
Conditions
Brief summary
The purpose of this study is to investigate whether 6 months treatment with the cholesterol-lowering drug rosuvastatin may reduce visceral fat tissue in obese middle aged men.
Detailed description
The accumulation of intra-abdominal fat has been suggested to be of primary importance in the development of the metabolic syndrome and associated metabolic disturbances and it has been hypothesized that a selective reduction of visceral fat tissue would improve the symptoms of the metabolic syndrome. Treatment with statins decrease levels of LDL-cholesterol and reduce coronary artery disease (CAD) events. Although it is widely accepted that the majority of benefit obtained with statins is a direct result of their lipid-lowering properties, they also demonstrate additional cholesterol-independent or pleiotropic effects. The results of experimental studies have now shown that statins decrease fat mass in the visceral region in an animal model. In the present study, we will investigate whether statins can decrease visceral obesity in humans.
Interventions
DRUGRosuvastatin
10 mg once daily
once daily
Sponsors
Sahlgrenska University Hospital
Göteborg University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
40 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Male patients between 40 and 65 years of age. * Abdominal obesity * Dyslipidemia * Written informed consent.
Exclusion criteria
* Uncontrolled hypertension * Diabetes mellitus * Severe liver disease * Severely reduced renal function * Uncontrolled endocrine disorders * History of or ongoing malignant disease * Patients with known myopathic disease * Recent alcohol or drug abuse * Weight loss or weight gain during the three months prior to screening. * Ongoing treatment with statins * Ongoing treatment with calcineurin-inhibitors * Ongoing treatment with anti-inflammatory drugs * Received an investigational drug within 30 days prior to screening. * Strong clinical indication for statin treatment * In the Principal Investigator's opinion, the patient has other clinically significant cardiac, oncologic, neurologic or psychiatric disease that could be adversely affected by Study participation. * For any reason the patient is considered by the Principal Investigator to be an unsuitable candidate to participate in the Study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in Visceral Adipose Tissue Area Measured by Computed Tomography. | 6 months |
Secondary
| Measure | Time frame |
|---|---|
| Change in Subcutaneous Adipose Tissue Area | 6 months |
| Change in the Ratio Between Intra-abdominal and Subcutaneous Tissue Area Measured by CT. | 6 months |
| Change in Hepatic Fat Infiltration Measured by CT. | 6 months |
| Change in Body Weight | 6 months |
| Change in LDL | 6 months |
Countries
Sweden
Participant flow
Recruitment details
From May 2006 to July 2007 a total of 78 subjects were screened at the Sahlgrenska Hospital. Among these, 59 fulfilled all inclusion and no exclusion criteria and were randomized to treatment. During follow-up 5 patients (7 %) withdrew from the study, resulting in 54 patients who completed the study, comprising 27 patients in each study group.
Pre-assignment details
Among patients that were screened 19 patients did not fulfill inclusion criteria or displayed exclusion criteria and did not enter the study.
Participants by arm
| Arm | Count |
|---|---|
| Rosuvastatin | 30 |
| Placebo for Rosuvastatin | 29 |
| Total | 59 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Rosuvastatin | Placebo for Rosuvastatin | Total |
|---|---|---|---|
| Age, Continuous | 54 years STANDARD_DEVIATION 5.2 | 55 years STANDARD_DEVIATION 4.1 | 54 years STANDARD_DEVIATION 4.7 |
| Age, Customized Between 18 and 65 years | 30 participants | 29 participants | 59 participants |
| Current smoker NO | 27 participants | 23 participants | 50 participants |
| Current smoker YES | 3 participants | 6 participants | 9 participants |
| Fasting glucose | 5.3 mmol/L STANDARD_DEVIATION 0.5 | 5.3 mmol/L STANDARD_DEVIATION 0.5 | 5.3 mmol/L STANDARD_DEVIATION 0.5 |
| Fasting insulin | 12 IU STANDARD_DEVIATION 4.8 | 13 IU STANDARD_DEVIATION 9.4 | 12 IU STANDARD_DEVIATION 8.5 |
| Height | 1.82 m STANDARD_DEVIATION 0.06 | 1.80 m STANDARD_DEVIATION 0.07 | 1.81 m STANDARD_DEVIATION 0.07 |
| Hypertension NO | 22 participants | 22 participants | 44 participants |
| Hypertension YES | 8 participants | 7 participants | 15 participants |
| LDL cholesterol | 3.59 mmol/L STANDARD_DEVIATION 0.78 | 3.77 mmol/L STANDARD_DEVIATION 0.79 | 3.69 mmol/L STANDARD_DEVIATION 0.74 |
| Liver density | 52 Hounsfield units STANDARD_DEVIATION 10 | 49 Hounsfield units STANDARD_DEVIATION 14 | 50 Hounsfield units STANDARD_DEVIATION 12 |
| Region of Enrollment Sweden | 30 participants | 29 participants | 59 participants |
| Sex/Gender, Customized Male | 30 participants | 29 participants | 59 participants |
| Subcutaneous adipose tissue area | 289 cm2 STANDARD_DEVIATION 69 | 310 cm2 STANDARD_DEVIATION 101 | 300 cm2 STANDARD_DEVIATION 86 |
| Visceral adipose tissue area | 221 cm2 STANDARD_DEVIATION 66 | 219 cm2 STANDARD_DEVIATION 73 | 220 cm2 STANDARD_DEVIATION 69 |
| Visceral/subcutaneous adipose tissue area ratio | 0.79 ratio STANDARD_DEVIATION 0.25 | 0.75 ratio STANDARD_DEVIATION 0.27 | 0.77 ratio STANDARD_DEVIATION 0.26 |
| Weight | 100 kg STANDARD_DEVIATION 12 | 100 kg STANDARD_DEVIATION 13 | 100 kg STANDARD_DEVIATION 13 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 30 | 5 / 29 |
| serious Total, serious adverse events | 3 / 30 | 1 / 29 |
Outcome results
Primary
Change in Visceral Adipose Tissue Area Measured by Computed Tomography.
Time frame: 6 months
Population: Per protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rosuvastatin | Change in Visceral Adipose Tissue Area Measured by Computed Tomography. | -1.5 cm2 | Standard Deviation 27 |
| Placebo for Rosuvastatin | Change in Visceral Adipose Tissue Area Measured by Computed Tomography. | 2.8 cm2 | Standard Deviation 26 |
Secondary
Change in Body Weight
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rosuvastatin | Change in Body Weight | 0.2 kg | Standard Deviation 2.6 |
| Placebo for Rosuvastatin | Change in Body Weight | 0.5 kg | Standard Deviation 1.5 |
Secondary
Change in Hepatic Fat Infiltration Measured by CT.
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rosuvastatin | Change in Hepatic Fat Infiltration Measured by CT. | 0 Hounsfield units | Standard Deviation 5.2 |
| Placebo for Rosuvastatin | Change in Hepatic Fat Infiltration Measured by CT. | -2 Hounsfield units | Standard Deviation 5 |
Secondary
Change in LDL
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rosuvastatin | Change in LDL | -1.4 mmol/L | Standard Deviation 0.9 |
| Placebo for Rosuvastatin | Change in LDL | -0.1 mmol/L | Standard Deviation 0.9 |
Secondary
Change in Subcutaneous Adipose Tissue Area
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rosuvastatin | Change in Subcutaneous Adipose Tissue Area | 10 cm2 | Standard Deviation 34 |
| Placebo for Rosuvastatin | Change in Subcutaneous Adipose Tissue Area | 1 cm2 | Standard Deviation 15 |
Secondary
Change in the Ratio Between Intra-abdominal and Subcutaneous Tissue Area Measured by CT.
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rosuvastatin | Change in the Ratio Between Intra-abdominal and Subcutaneous Tissue Area Measured by CT. | -0.02 ratio | Standard Deviation 0.11 |
| Placebo for Rosuvastatin | Change in the Ratio Between Intra-abdominal and Subcutaneous Tissue Area Measured by CT. | 0.01 ratio | Standard Deviation 0.08 |