Hyperlipoproteinemia, Metabolic Syndrome
Conditions
Brief summary
The study is designed to evaluate the effect of Niacin/Laropiprant on postprandial lipoprotein metabolism, postprandial glucose metabolism, postprandial monocyte function, and postprandial biomarkers of endothelial dysfunction and inflammation.
Interventions
DRUGNiacin/ Laropiprant
1000/ 20 mg first 4 weeks, 2000/40 mg next 8 weeks; daily
Sponsors
Ludwig-Maximilians - University of Munich
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Male subjects or postmenopausal female subjects aged between 19-70 years * High risk patients (PROCAM risk ≥20%) on a stable statin-therapy, but at least simvastatin 20 mg/d * HDL-cholesterol ≤50 mg/dl and /or triglycerides 150-400 mg/dl and/or LDL-cholesterol 70 - 150 mg/dl * Lipoprotein (a) \< 30 mg/dl * Patients may have normal glucose metabolism (normal HOMA), be insulin resistant (abnormal HOMA), have impaired fasting glucose or impaired glucose tolerance but not diabetes mellitus. * Without niacin therapy for at least 6 months * Dosage of any concomitant medication has been stable for at least 3 weeks * If female, postmenopausal (absence of menstruation for at least 12 months or absence of menstruation \> 6 months with FSH \> 40 ng/ml respectively oestrogen \< 20 pg/ml)
Exclusion criteria
* Subjects with additional causes for hyperlipoproteinemia * Diabetes mellitus or antidiabetic medication * Subject has history of cardiovascular ischemia in previous 3 months or acute myocardial infarction or unstable angina * History of psychiatric disorder or cognitive impairment that would interfere with participation in the study * History of alcoholism * Contraindication against niacin and/or laropiprant * Subject has participated in an investigational study within 30 days prior to study initiation * Fasting triglycerides \>400 mg/dl * Life-threatening disease (e.g. cancer) * Renal insufficiency (GFR ≤ 30 ml/min ) * Major hepatic impairment * Known allergic reaction/intolerance against niacin and/or laropiprant * Active peptic ulcer disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incremental Area Under the Plasma Triglyceride Curve Over 8 Hours Following a Standardized Oral Fat Tolerance Test | baseline and 12 weeks after treatment | Percent change of incremental AUC at 12 weeks compared to baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| HDL Cholesterol | baseline and 12 weeks after treatment | Percent change of HDL-cholesterol at 12 weeks compared to baseline. |
| Fasting Triglycerides | baseline and 12 weeks after treatment | Percent change of fasting triglycerides at 12 weeks compared to baseline |
Other
| Measure | Time frame | Description |
|---|---|---|
| LDL-cholesterol | baseline and 12 weeks after treatment | Percent change of LDL-cholesterol at 12 weeks compared to baseline |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Niacin/ Laropiprant Niacin/ Laropiprant: 1000/ 20 mg first 4 weeks, 2000/40 mg next 8 weeks; daily | 12 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Niacin/ Laropiprant |
|---|---|
| Age, Continuous | 64 years STANDARD_DEVIATION 9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 12 Participants |
| Region of Enrollment Germany | 12 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 12 |
| serious Total, serious adverse events | 0 / 12 |
Outcome results
Primary
Incremental Area Under the Plasma Triglyceride Curve Over 8 Hours Following a Standardized Oral Fat Tolerance Test
Percent change of incremental AUC at 12 weeks compared to baseline.
Time frame: baseline and 12 weeks after treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Niacin/ Laropiprant | Incremental Area Under the Plasma Triglyceride Curve Over 8 Hours Following a Standardized Oral Fat Tolerance Test | -28 percentage change | Standard Deviation 5 |
Secondary
Fasting Triglycerides
Percent change of fasting triglycerides at 12 weeks compared to baseline
Time frame: baseline and 12 weeks after treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Niacin/ Laropiprant | Fasting Triglycerides | -26 percentage change | Standard Deviation 15 |
Secondary
HDL Cholesterol
Percent change of HDL-cholesterol at 12 weeks compared to baseline.
Time frame: baseline and 12 weeks after treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Niacin/ Laropiprant | HDL Cholesterol | 17 percentage change | Standard Deviation 6 |
Other Pre-specified
LDL-cholesterol
Percent change of LDL-cholesterol at 12 weeks compared to baseline
Time frame: baseline and 12 weeks after treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Niacin/ Laropiprant | LDL-cholesterol | -20 percentage change | Standard Deviation 8 |